The interplay between oxidative stress and bioenergetic failure in neuropsychiatric illnesses: can we explain it and can we treat it?

Abstract

Nitro-oxidative stress and lowered antioxidant defences play a key role in neuropsychiatric disorders such as major depression, bipolar disorder and schizophrenia. The first part of this paper details mitochondrial antioxidant mechanisms and their importance in reactive oxygen species (ROS) detoxification, including details of NO networks, the roles of H2O2 and the thioredoxin/peroxiredoxin system, and the relationship between mitochondrial respiration and NADPH production. The second part highlights and identifies the causes of the multiple pathological sequelae arising from self-amplifying increases in mitochondrial ROS production and bioenergetic failure. Particular attention is paid to NAD+ depletion as a core cause of pathology; detrimental effects of raised ROS and reactive nitrogen species on ATP and NADPH generation; detrimental effects of oxidative and nitrosative stress on the glutathione and thioredoxin systems; and the NAD+-induced signalling cascade, including the roles of SIRT1, SIRT3, PGC-1α, the FOXO family of transcription factors, Nrf1 and Nrf2. The third part discusses proposed therapeutic interventions aimed at mitigating such pathology, including the use of the NAD+ precursors nicotinamide mononucleotide and nicotinamide riboside, both of which rapidly elevate levels of NAD+ in the brain and periphery following oral administration; coenzyme Q10 which, when given with the aim of improving mitochondrial function and reducing nitro-oxidative stress in the brain, may be administered via the use of mitoquinone, which is in essence ubiquinone with an attached triphenylphosphonium cation; and N-acetylcysteine, which is associated with improved mitochondrial function in the brain and produces significant decreases in oxidative and nitrosative stress in a dose-dependent manner.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E (2011) Lower whole blood glutathione peroxidase (GPX) activity in depression, but not in myalgic encephalomyelitis/chronic fatigue syndrome: another pathway that may be associated with coronary artery disease and neuroprogression in depression. Neuro endocrinol Lett 32(2):133–140

    PubMed  Google Scholar 

  2. 2.

    Maes M, Landucci Bonifacio K, Morelli NR, Vargas HO, Barbosa DS, Carvalho AF, Nunes SOV (2019) Major differences in neurooxidative and neuronitrosative stress pathways between major depressive disorder and types I and II bipolar disorder. Mol Neurobiol 56(1):141–156. https://doi.org/10.1007/s12035-018-1051-7

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Berk M, Conus P, Kapczinski F, Andreazza AC, Yucel M, Wood SJ, Pantelis C, Malhi GS, Dodd S, Bechdolf A, Amminger GP, Hickie IB, McGorry PD (2010) From neuroprogression to neuroprotection: implications for clinical care. Med J Aust 193(S4):S36–40

    PubMed  Google Scholar 

  4. 4.

    Liu M-L, Zhang X-T, Du X-Y, Fang Z, Liu Z, Xu Y, Zheng P, Xu X-J, Cheng P-F, Huang T, Bai S-J, Zhao L-B, Qi Z-G, Shao W-H, Xie P (2015) Severe disturbance of glucose metabolism in peripheral blood mononuclear cells of schizophrenia patients: a targeted metabolomic study. J Transl Med 13:226–226. https://doi.org/10.1186/s12967-015-0540-y

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Solanki N, Alkadhi I, Atrooz F, Patki G, Salim S (2015) Grape powder prevents cognitive, behavioral, and biochemical impairments in a rat model of posttraumatic stress disorder. Nutr Res 35(1):65–75. https://doi.org/10.1016/j.nutres.2014.11.008

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Solanki N, Salvi A, Patki G, Salim S (2017) Modulating oxidative stress relieves stress-induced behavioral and cognitive impairments in rats. Int J Neuropsychopharmacol 20(7):550–561. https://doi.org/10.1093/ijnp/pyx017

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Salim S (2014) Oxidative stress and psychological disorders. Curr Neuropharmacol 12(2):140–147. https://doi.org/10.2174/1570159X11666131120230309

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Salim S (2017) Oxidative stress and the central nervous system. J Pharmacol Exp Ther 360(1):201–205. https://doi.org/10.1124/jpet.116.237503

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Fraguas D, Díaz-Caneja CM, Ayora M, Hernández-Álvarez F, Rodríguez-Quiroga A, Recio S, Leza JC, Arango C (2019) Oxidative stress and inflammation in first-episode psychosis: a systematic review and meta-analysis. Schizophr Bull 45(4):742–751. https://doi.org/10.1093/schbul/sby125

    Article  PubMed  Google Scholar 

  10. 10.

    Knorr U, Simonsen AH, Roos P, Weimann A, Henriksen T, Christensen E-M, Vinberg M, Mikkelsen RL, Kirkegaard T, Jensen RN, Akhøj M, Forman J, Poulsen HE, Hasselbalch SG, Kessing LV (2019) Cerebrospinal fluid oxidative stress metabolites in patients with bipolar disorder and healthy controls: a longitudinal case-control study. Transl Psychiatry 9(1):325. https://doi.org/10.1038/s41398-019-0664-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Black CN, Bot M, Scheffer PG, Cuijpers P, Penninx BW (2015) Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology. https://doi.org/10.1016/j.psyneuen.2014.09.025

    Article  PubMed  Google Scholar 

  12. 12.

    Michel TM, Pülschen D, Thome J (2012) The role of oxidative stress in depressive disorders. Curr Pharm Des 18(36):5890–5899. https://doi.org/10.2174/138161212803523554

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Singh N, McMahon H, Bilderbeck A, Reed ZE, Tunbridge E, Brett D, Geddes JR, Churchill GC, Goodwin GM (2019) Plasma glutathione suggests oxidative stress is equally present in early- and late-onset bipolar disorder. Bipolar Disord 21(1):61–67. https://doi.org/10.1111/bdi.12640

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Morris G, Puri BK, Walker AJ, Berk M, Walder K, Bortolasci CC, Marx W, Carvalho AF, Maes M (2019) The compensatory antioxidant response system with a focus on neuroprogressive disorders. Prog Neuro-psychopharmacol Biol Psychiatry. https://doi.org/10.1016/j.pnpbp.2019.109708

    Article  Google Scholar 

  15. 15.

    Leonard B, Maes M (2012) Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 36(2):764–785. https://doi.org/10.1016/j.neubiorev.2011.12.005

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Morris G, Walder K, McGee SL, Dean OM, Tye SJ, Maes M, Berk M (2017) A model of the mitochondrial basis of bipolar disorder. Neurosci Biobehav Rev 74(Pt A):1–20. https://doi.org/10.1016/j.neubiorev.2017.01.014

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Callaly E, Walder K, Morris G, Maes M, Debnath M, Berk M (2015) Mitochondrial dysfunction in the pathophysiology of bipolar disorder: effects of pharmacotherapy. Mini Rev Med Chem 15(5):355–365

    CAS  Article  Google Scholar 

  18. 18.

    Maes M, Galecki P, Chang YS, Berk M (2011) A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 35(3):676–692. https://doi.org/10.1016/j.pnpbp.2010.05.004

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Owe-Larsson B, Ekdahl K, Edbom T, Osby U, Karlsson H, Lundberg C, Lundberg M (2011) Increased plasma levels of thioredoxin-1 in patients with first episode psychosis and long-term schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 35(4):1117–1121. https://doi.org/10.1016/j.pnpbp.2011.03.012

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Nasyrova RF, Ivashchenko DV, Ivanov MV, Neznanov NG (2015) Role of nitric oxide and related molecules in schizophrenia pathogenesis: biochemical, genetic and clinical aspects. Front Physiol. https://doi.org/10.3389/fphys.2015.00139

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Zhang XY, Chen DC, Xiu MH, Wang F, Qi LY, Sun HQ, Chen S, He SC, Wu GY, Haile CN, Kosten TA, Lu L, Kosten TR (2009) The novel oxidative stress marker thioredoxin is increased in first-episode schizophrenic patients. Schizophr Res 113(2):151–157. https://doi.org/10.1016/j.schres.2009.05.016

    Article  PubMed  Google Scholar 

  22. 22.

    Aydin EP, Genc A, Dalkiran M, Uyar ET, Deniz I, Ozer OA, Karamustafalioglu KO (2018) Thioredoxin is not a marker for treatment-resistance depression but associated with cognitive function: an rTMS study. Prog Neuropsychopharmacol Biol Psychiatry 80(Pt C):322–328. https://doi.org/10.1016/j.pnpbp.2017.04.025

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Bas A, Gultekin G, Incir S, Bas TO, Emul M, Duran A (2017) Level of serum thioredoxin and correlation with neurocognitive functions in patients with schizophrenia using clozapine and other atypical antipsychotics. Psychiatry Res 247:84–89. https://doi.org/10.1016/j.psychres.2016.11.021

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Genc K, Genc S (2009) Oxidative stress and dysregulated Nrf2 activation in the pathogenesis of schizophrenia. Biosci Hypotheses 2(1):16–18. https://doi.org/10.1016/j.bihy.2008.10.005

    Article  Google Scholar 

  25. 25.

    Genc A, Kalelioglu T, Karamustafalioglu N, Tasdemir A, Gungor FC, Genc ES, Incir S, Ilnem C, Emul M (2015) Level of plasma thioredoxin in male patients with manic episode at initial and post-electroconvulsive or antipsychotic treatment. Psychiatry Clin Neurosci 69(6):344–350. https://doi.org/10.1111/pcn.12244

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Nucifora LG, Tanaka T, Hayes LN, Kim M, Lee BJ, Matsuda T, Nucifora FC Jr, Sedlak T, Mojtabai R, Eaton W, Sawa A (2017) Reduction of plasma glutathione in psychosis associated with schizophrenia and bipolar disorder in translational psychiatry. Transl Psychiatry 7(8):e1215–e1215. https://doi.org/10.1038/tp.2017.178

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Freed RD, Hollenhorst CN, Weiduschat N, Mao X, Kang G, Shungu DC, Gabbay V (2017) A pilot study of cortical glutathione in youth with depression. Psychiatry Res 270:54–60. https://doi.org/10.1016/j.pscychresns.2017.10.001

    Article  PubMed Central  Google Scholar 

  28. 28.

    Lapidus KAB, Gabbay V, Mao X, Johnson A, Murrough JW, Mathew SJ, Shungu DC (2014) In vivo 1H MRS study of potential associations between glutathione, oxidative stress and anhedonia in major depressive disorder. Neurosci Lett 569:74–79. https://doi.org/10.1016/j.neulet.2014.03.056

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Gawryluk JW, Wang J-F, Andreazza AC, Shao L, Young LT (2011) Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol 14(1):123–130. https://doi.org/10.1017/s1461145710000805

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Yao JK, Reddy RD, van Kammen DP (1999) Human plasma glutathione peroxidase and symptom severity in schizophrenia. Biol Psychiatry 45(11):1512–1515. https://doi.org/10.1016/s0006-3223(98)00184-x

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Martin-Hernandez D, Caso JR, Javier Meana J, Callado LF, Madrigal JLM, Garcia-Bueno B, Leza JC (2018) Intracellular inflammatory and antioxidant pathways in postmortem frontal cortex of subjects with major depression: effect of antidepressants. J Neuroinflamm 15(1):251. https://doi.org/10.1186/s12974-018-1294-2

    CAS  Article  Google Scholar 

  32. 32.

    Zhang JC, Yao W, Dong C, Han M, Shirayama Y, Hashimoto K (2018) Keap1-Nrf2 signaling pathway confers resilience versus susceptibility to inescapable electric stress. Eur Arch Psychiatry Clin Neurosci 268(8):865–870. https://doi.org/10.1007/s00406-017-0848-0

    Article  PubMed  Google Scholar 

  33. 33.

    Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS (2010) Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proc Natl Acad Sci USA 107(6):2669–2674. https://doi.org/10.1073/pnas.0910658107

    Article  PubMed  Google Scholar 

  34. 34.

    Elhaik E, Zandi P (2015) Dysregulation of the NF-kappaB pathway as a potential inducer of bipolar disorder. J Psychiatr Res 70:18–27. https://doi.org/10.1016/j.jpsychires.2015.08.009

    Article  PubMed  Google Scholar 

  35. 35.

    Volk DW, Moroco AE, Roman KM, Edelson JR, Lewis DA (2019) The role of the nuclear factor-kappaB transcriptional complex in cortical immune activation in schizophrenia. Biol Psychiatry 85(1):25–34. https://doi.org/10.1016/j.biopsych.2018.06.015

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Wardyn JD, Ponsford AH, Sanderson CM (2015) Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways. Biochem Soc Trans 43(4):621–626. https://doi.org/10.1042/BST20150014

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A (2013) Antagonistic crosstalk between NF-kappaB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal 25(10):1939–1948. https://doi.org/10.1016/j.cellsig.2013.06.007

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Albensi BC (2019) What is nuclear factor kappa B (NF-κB) doing in and to the mitochondrion? Front Cell Dev Biol. https://doi.org/10.3389/fcell.2019.00154

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Kim Y, Santos R, Gage FH, Marchetto MC (2017) Molecular mechanisms of bipolar disorder: progress made and future challenges. Front Cell Neurosci. https://doi.org/10.3389/fncel.2017.00030

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Scaini G, Rezin GT, Carvalho AF, Streck EL, Berk M, Quevedo J (2016) Mitochondrial dysfunction in bipolar disorder: evidence, pathophysiology and translational implications. Neurosci Biobehav Rev 68:694–713. https://doi.org/10.1016/j.neubiorev.2016.06.040

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Gassen NC, Rein T (2019) Is there a role of autophagy in depression and antidepressant action? Front Psychiatry. https://doi.org/10.3389/fpsyt.2019.00337

    Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Bansal Y, Kuhad A (2016) Mitochondrial dysfunction in depression. Curr Neuropharmacol 14(6):610–618. https://doi.org/10.2174/1570159X14666160229114755

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Flippo KH, Strack S (2017) An emerging role for mitochondrial dynamics in schizophrenia. Schizophr Res 187:26–32. https://doi.org/10.1016/j.schres.2017.05.003

    Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Roberts RC (2017) Postmortem studies on mitochondria in schizophrenia. Schizophr Res 187:17–25. https://doi.org/10.1016/j.schres.2017.01.056

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Morris G, Walder K, Carvalho AF, Tye SJ, Lucas K, Berk M, Maes M (2018) The role of hypernitrosylation in the pathogenesis and pathophysiology of neuroprogressive diseases. Neurosci Biobehav Rev 84:453–469. https://doi.org/10.1016/j.neubiorev.2017.07.017

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Klauser P, Xin L, Fournier M, Griffa A, Cleusix M, Jenni R, Cuenod M, Gruetter R, Hagmann P, Conus P, Baumann PS, Do KQ (2018) N-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: a double-blind randomized placebo-controlled trial. Transl Psychiatry 8(1):220. https://doi.org/10.1038/s41398-018-0266-8

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Mullier E, Roine T, Griffa A, Xin L, Baumann PS, Klauser P, Cleusix M, Jenni R, Alemàn-Gómez Y, Gruetter R, Conus P, Do KQ, Hagmann P (2019) N-acetyl-cysteine supplementation improves functional connectivity within the cingulate cortex in early psychosis: a pilot study. Int J Neuropsychopharmacol 22(8):478–487. https://doi.org/10.1093/ijnp/pyz022

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Berk M, Turner A, Malhi GS, Ng CH, Cotton SM, Dodd S, Samuni Y, Tanious M, McAulay C, Dowling N, Sarris J, Owen L, Waterdrinker A, Smith D, Dean OM (2019) A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo. BMC Med 17(1):18. https://doi.org/10.1186/s12916-019-1257-1

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Forester BP, Harper DG, Georgakas J, Ravichandran C, Madurai N, Cohen BM (2015) Antidepressant effects of open label treatment with coenzyme Q10 in geriatric bipolar depression. J Clin Psychopharmacol 35(3):338–340. https://doi.org/10.1097/JCP.0000000000000326

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Mehrpooya M, Yasrebifar F, Haghighi M, Mohammadi Y, Jahangard L (2018) Evaluating the effect of coenzyme Q10 augmentation on treatment of bipolar depression: a double-blind controlled clinical trial. J Clin Psychopharmacol 38(5):460–466. https://doi.org/10.1097/jcp.0000000000000938

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Maguire A, Hargreaves A, Gill M (2018) Coenzyme Q10 and neuropsychiatric and neurological disorders: relevance for schizophrenia. Nutr Neurosci. https://doi.org/10.1080/1028415x.2018.1556481

    Article  PubMed  Google Scholar 

  52. 52.

    Morris G, Anderson G, Berk M, Maes M (2013) Coenzyme Q10 depletion in medical and neuropsychiatric disorders: potential repercussions and therapeutic implications. Mol Neurobiol 48(3):883–903. https://doi.org/10.1007/s12035-013-8477-8

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Gerwyn M, Maes M (2017) Mechanisms explaining muscle fatigue and muscle pain in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a review of recent findings. Curr Rheumatol Rep 19(1):1. https://doi.org/10.1007/s11926-017-0628-x

    Article  PubMed  Google Scholar 

  54. 54.

    Ezerina D, Takano Y, Hanaoka K, Urano Y, Dick TP (2018) N-acetyl cysteine functions as a fast-acting antioxidant by triggering intracellular H2S and sulfane sulfur production. Cell Chem Biol 25(4):447–459.e444. https://doi.org/10.1016/j.chembiol.2018.01.011

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Zuhra K, Tome CS, Masi L, Giardina G, Paulini G, Malagrino F, Forte E, Vicente JB, Giuffre A (2019) N-acetylcysteine serves as substrate of 3-mercaptopyruvate sulfurtransferase and stimulates sulfide metabolism in colon cancer cells. Cells. https://doi.org/10.3390/cells8080828

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Lambeth JD, Neish AS (2014) Nox enzymes and new thinking on reactive oxygen: a double-edged sword revisited. Annu Rev Pathol 9:119–145. https://doi.org/10.1146/annurev-pathol-012513-104651

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Ma MW, Wang J, Dhandapani KM, Brann DW (2017) NADPH oxidase 2 regulates NLRP3 inflammasome activation in the brain after traumatic brain injury. Oxid Med Cell Longev 2017:18. https://doi.org/10.1155/2017/6057609

    CAS  Article  Google Scholar 

  58. 58.

    Angelova PR, Abramov AY (2018) Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Lett 592(5):692–702. https://doi.org/10.1002/1873-3468.12964

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Miller EW, Tulyathan O, Isacoff EY, Chang CJ (2007) Molecular imaging of hydrogen peroxide produced for cell signaling. Nat Chem Biol 3(5):263–267. https://doi.org/10.1038/nchembio871

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    Groeger G, Quiney C, Cotter TG (2009) Hydrogen peroxide as a cell-survival signaling molecule. Antioxid Redox Signal 11(11):2655–2671. https://doi.org/10.1089/ars.2009.2728

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Woolley JF, Corcoran A, Groeger G, Landry WD, Cotter TG (2013) Redox-regulated growth factor survival signaling. Antioxid Redox Signal 19(15):1815–1827. https://doi.org/10.1089/ars.2012.5028

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Bao L, Avshalumov MV, Rice ME (2005) Partial mitochondrial inhibition causes striatal dopamine release suppression and medium spiny neuron depolarization via H2O2 elevation, not ATP depletion. J Neurosci 25(43):10029–10040. https://doi.org/10.1523/jneurosci.2652-05.2005

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Rice ME (2011) H2O2: a dynamic neuromodulator. Neuroscientist 17(4):389–406. https://doi.org/10.1177/1073858411404531

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Dantzler HA, Matott MP, Martinez D, Kline DD (2019) Hydrogen peroxide inhibits neurons in the paraventricular nucleus of the hypothalamus via potassium channel activation. Am J Physiol Regul Integr Comp Physiol 317(1):R121–r133. https://doi.org/10.1152/ajpregu.00054.2019

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    Lee CR, Patel JC, O'Neill B, Rice ME (2015) Inhibitory and excitatory neuromodulation by hydrogen peroxide: translating energetics to information. J Physiol 593(16):3431–3446. https://doi.org/10.1113/jphysiol.2014.273839

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Guo C, Sun L, Chen X, Zhang D (2013) Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regeneration Res 8(21):2003–2014. https://doi.org/10.3969/j.issn.1673-5374.2013.21.009

    CAS  Article  Google Scholar 

  67. 67.

    Kausar S, Wang F, Cui H (2018) The role of mitochondria in reactive oxygen species generation and its implications for neurodegenerative diseases. Cells 7(12):274. https://doi.org/10.3390/cells7120274

    CAS  Article  PubMed Central  Google Scholar 

  68. 68.

    Morris G, Berk M, Carvalho AF, Maes M, Walker AJ, Puri BK (2018) Why should neuroscientists worry about iron? The emerging role of ferroptosis in the pathophysiology of neuroprogressive diseases. Behav Brain Res 341:154–175. https://doi.org/10.1016/j.bbr.2017.12.036

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Morris G, Berk M (2015) The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med 13(1):68. https://doi.org/10.1186/s12916-015-0310-y

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Cuperfain AB, Zhang ZL, Kennedy JL, Gonçalves VF (2018) The complex interaction of mitochondrial genetics and mitochondrial pathways in psychiatric disease. Mol Neuropsychiatry 4(1):52–69. https://doi.org/10.1159/000488031

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Kakkar P, Singh BK (2007) Mitochondria: a hub of redox activities and cellular distress control. Mol Cell Biochem 305(1–2):235–253. https://doi.org/10.1007/s11010-007-9520-8

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552(Pt 2):335–344. https://doi.org/10.1113/jphysiol.2003.049478

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Morris G, Maes M (2014) Oxidative and nitrosative stress and immune-inflammatory pathways in patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Curr Neuropharmacol 12(2):168–185. https://doi.org/10.2174/1570159x11666131120224653

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Lucas K, Morris G, Anderson G, Maes M (2015) The toll-like receptor radical cycle pathway: a new drug target in immune-related chronic fatigue. CNS Neurol Disorders 14(7):838–854

    CAS  Article  Google Scholar 

  75. 75.

    Pope S, Land JM, Heales SJ (2008) Oxidative stress and mitochondrial dysfunction in neurodegeneration; cardiolipin a critical target? Biochim Biophys Acta 1777(7–8):794–799. https://doi.org/10.1016/j.bbabio.2008.03.011

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Paradies G, Petrosillo G, Paradies V, Ruggiero FM (2011) Mitochondrial dysfunction in brain aging: role of oxidative stress and cardiolipin. Neurochem Int 58(4):447–457. https://doi.org/10.1016/j.neuint.2010.12.016

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Saki M, Prakash A (2017) DNA damage related crosstalk between the nucleus and mitochondria. Free Radic Biol Med 107:216–227. https://doi.org/10.1016/j.freeradbiomed.2016.11.050

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Dikalov S (2011) Cross talk between mitochondria and NADPH oxidases. Free Radic Biol Med 51(7):1289–1301. https://doi.org/10.1016/j.freeradbiomed.2011.06.033

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Daiber A, Di Lisa F, Oelze M, Kroller-Schon S, Steven S, Schulz E, Munzel T (2017) Crosstalk of mitochondria with NADPH oxidase via reactive oxygen and nitrogen species signalling and its role for vascular function. Br J Pharmacol 174(12):1670–1689. https://doi.org/10.1111/bph.13403

    CAS  Article  PubMed  Google Scholar 

  80. 80.

    Kroller-Schon S, Steven S, Kossmann S, Scholz A, Daub S, Oelze M, Xia N, Hausding M, Mikhed Y, Zinssius E, Mader M, Stamm P, Treiber N, Scharffetter-Kochanek K, Li H, Schulz E, Wenzel P, Munzel T, Daiber A (2014) Molecular mechanisms of the crosstalk between mitochondria and NADPH oxidase through reactive oxygen species-studies in white blood cells and in animal models. Antioxid Redox Signal 20(2):247–266. https://doi.org/10.1089/ars.2012.4953

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Fransen M, Lismont C, Walton P (2017) The peroxisome-mitochondria connection: how and why? Int J Mol Sci. https://doi.org/10.3390/ijms18061126

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Lismont C, Nordgren M, Van Veldhoven PP, Fransen M (2015) Redox interplay between mitochondria and peroxisomes. Front Cell Dev Biol 3:35–35. https://doi.org/10.3389/fcell.2015.00035

    Article  PubMed  PubMed Central  Google Scholar 

  83. 83.

    Schulz E, Wenzel P, Munzel T, Daiber A (2014) Mitochondrial redox signaling: Interaction of mitochondrial reactive oxygen species with other sources of oxidative stress. Antioxid Redox Signal 20(2):308–324. https://doi.org/10.1089/ars.2012.4609

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Morris G, Walker AJ, Berk M, Maes M, Puri BK (2018) Cell death pathways: a novel therapeutic approach for neuroscientists. Mol Neurobiol 55(7):5767–5786. https://doi.org/10.1007/s12035-017-0793-y

    CAS  Article  PubMed  Google Scholar 

  85. 85.

    Galley HF (2011) Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth 107(1):57–64. https://doi.org/10.1093/bja/aer093

    CAS  Article  PubMed  Google Scholar 

  86. 86.

    Litvinova L, Atochin DN, Fattakhov N, Vasilenko M, Zatolokin P, Kirienkova E (2015) Nitric oxide and mitochondria in metabolic syndrome. Front Physiol. https://doi.org/10.3389/fphys.2015.00020

    Article  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Ghafourifar P, Cadenas E (2005) Mitochondrial nitric oxide synthase. Trends Pharmacol Sci 26(4):190–195. https://doi.org/10.1016/j.tips.2005.02.005

    CAS  Article  PubMed  Google Scholar 

  88. 88.

    Morris G, Berk M, Klein H, Walder K, Galecki P, Maes M (2017) Nitrosative stress, hypernitrosylation, and autoimmune responses to nitrosylated proteins: new pathways in neuroprogressive disorders including depression and chronic fatigue syndrome. Mol Neurobiol 54(6):4271–4291. https://doi.org/10.1007/s12035-016-9975-2

    CAS  Article  PubMed  Google Scholar 

  89. 89.

    Lopert P, Patel M (2014) Nicotinamide nucleotide transhydrogenase (Nnt) links the substrate requirement in brain mitochondria for hydrogen peroxide removal to the thioredoxin/peroxiredoxin (Trx/Prx) system. J Biol Chem 289(22):15611–15620. https://doi.org/10.1074/jbc.M113.533653

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Drechsel DA, Patel M (2010) Respiration-dependent H2O2 removal in brain mitochondria via the thioredoxin/peroxiredoxin system. J Biol Chem 285(36):27850–27858. https://doi.org/10.1074/jbc.M110.101196

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Treberg JR, Braun K, Selseleh P (2019) Mitochondria can act as energy-sensing regulators of hydrogen peroxide availability. Redox Biol 20:483–488. https://doi.org/10.1016/j.redox.2018.11.002

    CAS  Article  PubMed  Google Scholar 

  92. 92.

    Silva-Adaya D, Gonsebatt M, Guevara J (2014) Thioredoxin system regulation in the central nervous system: experimental models and clinical evidence. Oxid Med Cell Longev 2014:13. https://doi.org/10.1155/2014/590808

    CAS  Article  Google Scholar 

  93. 93.

    Holzerova E, Danhauser K, Haack TB, Kremer LS, Melcher M, Ingold I, Kobayashi S, Terrile C, Wolf P, Schaper J, Mayatepek E, Baertling F, Friedmann Angeli JP, Conrad M, Strom TM, Meitinger T, Prokisch H, Distelmaier F (2016) Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration. Brain 139(Pt 2):346–354. https://doi.org/10.1093/brain/awv350

    Article  PubMed  Google Scholar 

  94. 94.

    Cunniff B, Wozniak AN, Sweeney P, DeCosta K, Heintz NH (2014) Peroxiredoxin 3 levels regulate a mitochondrial redox setpoint in malignant mesothelioma cells. Redox Biol 3:79–87. https://doi.org/10.1016/j.redox.2014.11.003

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Hanschmann E-M, Godoy JR, Berndt C, Hudemann C, Lillig CH (2013) Thioredoxins, glutaredoxins, and peroxiredoxins–molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling. Antioxid Redox Signal 19(13):1539–1605. https://doi.org/10.1089/ars.2012.4599

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  96. 96.

    Brigelius-Flohe R, Maiorino M (2013) Glutathione peroxidases. Biochim Biophys Acta 1830(5):3289–3303. https://doi.org/10.1016/j.bbagen.2012.11.020

    CAS  Article  Google Scholar 

  97. 97.

    Couto N, Wood J, Barber J (2016) The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med 95:27–42. https://doi.org/10.1016/j.freeradbiomed.2016.02.028

    CAS  Article  PubMed  Google Scholar 

  98. 98.

    Kalinina EV, Chernov NN, Saprin AN (2008) Involvement of thio-, peroxi-, and glutaredoxins in cellular redox-dependent processes. Biochem Biokhimiia 73(13):1493–1510

    CAS  Article  Google Scholar 

  99. 99.

    Sugadev R, Ponnuswamy MN, Sekar K (2011) Structural analysis of NADPH depleted bovine liver catalase and its inhibitor complexes. Int J Biochem Mol Biol 2(1):67–77

    CAS  PubMed  PubMed Central  Google Scholar 

  100. 100.

    Morris G, Anderson G, Dean O, Berk M, Galecki P, Martin-Subero M, Maes M (2014) The glutathione system: a new drug target in neuroimmune disorders. Mol Neurobiol 50(3):1059–1084. https://doi.org/10.1007/s12035-014-8705-x

    CAS  Article  PubMed  Google Scholar 

  101. 101.

    Mari M, Morales A, Colell A, Garcia-Ruiz C, Fernandez-Checa JC (2009) Mitochondrial glutathione, a key survival antioxidant. Antioxid Redox Signal 11(11):2685–2700. https://doi.org/10.1089/ars.2009.2695

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Maroz A, Anderson RF, Smith RA, Murphy MP (2009) Reactivity of ubiquinone and ubiquinol with superoxide and the hydroperoxyl radical: implications for in vivo antioxidant activity. Free Radic Biol Med 46(1):105–109. https://doi.org/10.1016/j.freeradbiomed.2008.09.033

    CAS  Article  PubMed  Google Scholar 

  103. 103.

    Kc S, Carcamo JM, Golde DW (2005) Vitamin C enters mitochondria via facilitative glucose transporter 1 (Glut1) and confers mitochondrial protection against oxidative injury. FASEB J 19(12):1657–1667. https://doi.org/10.1096/fj.05-4107com

    CAS  Article  PubMed  Google Scholar 

  104. 104.

    Lauridsen C, Jensen SK (2012) alpha-Tocopherol incorporation in mitochondria and microsomes upon supranutritional vitamin E supplementation. Genes Nutr 7(4):475–482. https://doi.org/10.1007/s12263-012-0286-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Ekoue DN, He C, Diamond AM (1858) Manganese superoxide dismutase and glutathione peroxidase-1 contribute to the rise and fall of mitochondrial reactive oxygen species which drive oncogenesis. Biochim Biophys Acta 8:628–632. https://doi.org/10.1016/j.bbabio.2017.01.006

    CAS  Article  Google Scholar 

  106. 106.

    Handy DE, Lubos E, Yang Y, Galbraith JD, Kelly N, Zhang Y-Y, Leopold JA, Loscalzo J (2009) Glutathione peroxidase-1 regulates mitochondrial function to modulate redox-dependent cellular responses. J Biol Chem 284(18):11913–11921. https://doi.org/10.1074/jbc.M900392200

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  107. 107.

    De Simoni S, Linard D, Hermans E, Knoops B, Goemaere J (2013) Mitochondrial peroxiredoxin-5 as potential modulator of mitochondria-ER crosstalk in MPP+-induced cell death. J Neurochem 125(3):473–485. https://doi.org/10.1111/jnc.12117

    CAS  Article  PubMed  Google Scholar 

  108. 108.

    De Simoni S, Goemaere J, Knoops B (2008) Silencing of peroxiredoxin 3 and peroxiredoxin 5 reveals the role of mitochondrial peroxiredoxins in the protection of human neuroblastoma SH-SY5Y cells toward MPP+. Neurosci Lett 433(3):219–224. https://doi.org/10.1016/j.neulet.2007.12.068

    CAS  Article  PubMed  Google Scholar 

  109. 109.

    Sun C-C, Dong W-R, Shao T, Li J-Y, Zhao J, Nie L, Xiang L-X, Zhu G, Shao J-Z (2017) Peroxiredoxin 1 (Prx1) is a dual-function enzyme by possessing Cys-independent catalase-like activity. Biochem J 474(8):1373–1394. https://doi.org/10.1042/bcj20160851

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Peskin AV, Dickerhof N, Poynton RA, Paton LN, Pace PE, Hampton MB, Winterbourn CC (2013) Hyperoxidation of peroxiredoxins 2 and 3: rate constants for the reactions of the sulfenic acid of the peroxidatic cysteine. J Biol Chem 288(20):14170–14177. https://doi.org/10.1074/jbc.M113.460881

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  111. 111.

    Stanley BA, Sivakumaran V, Shi S, McDonald I, Lloyd D, Watson WH, Aon MA, Paolocci N (2011) Thioredoxin reductase-2 is essential for keeping low levels of H2O2 emission from isolated heart mitochondria. J Biol Chem 286(38):33669–33677. https://doi.org/10.1074/jbc.M111.284612

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  112. 112.

    Mailloux RJ (2018) Mitochondrial antioxidants and the maintenance of cellular hydrogen peroxide levels. Oxid Med Cell Longev 2018:7857251–7857251. https://doi.org/10.1155/2018/7857251

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  113. 113.

    Saccoccia F, Angelucci F, Boumis G, Carotti D, Desiato G, Miele AE, Bellelli A (2014) Thioredoxin reductase and its inhibitors. Curr Protein Pept Sci 15(6):621–646

    CAS  Article  Google Scholar 

  114. 114.

    Noh YH, Baek JY, Jeong W, Rhee SG, Chang TS (2009) Sulfiredoxin translocation into mitochondria plays a crucial role in reducing hyperoxidized peroxiredoxin III. J Biol Chem 284(13):8470–8477. https://doi.org/10.1074/jbc.M808981200

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  115. 115.

    Jeong EA, Jeon BT, Shin HJ, Kim N, Lee DH, Kim HJ, Kang SS, Cho GJ, Choi WS, Roh GS (2011) Ketogenic diet-induced peroxisome proliferator-activated receptor-gamma activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures. Exp Neurol 232(2):195–202. https://doi.org/10.1016/j.expneurol.2011.09.001

    CAS  Article  PubMed  Google Scholar 

  116. 116.

    Adimora NJ, Jones DP, Kemp ML (2010) A model of redox kinetics implicates the thiol proteome in cellular hydrogen peroxide responses. Antioxid Redox Signal 13(6):731–743. https://doi.org/10.1089/ars.2009.2968

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Rhee SG, Woo HA (2011) Multiple functions of peroxiredoxins: peroxidases, sensors and regulators of the intracellular messenger H(2)O(2), and protein chaperones. Antioxid Redox Signal 15(3):781–794. https://doi.org/10.1089/ars.2010.3393

    CAS  Article  PubMed  Google Scholar 

  118. 118.

    Rhee SG (2016) Overview on peroxiredoxin. Mol Cells 39(1):1–5. https://doi.org/10.14348/molcells.2016.2368

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  119. 119.

    Jeong W, Bae SH, Toledano MB, Rhee SG (2012) Role of sulfiredoxin as a regulator of peroxiredoxin function and regulation of its expression. Free Radic Biol Med 53(3):447–456. https://doi.org/10.1016/j.freeradbiomed.2012.05.020

    CAS  Article  PubMed  Google Scholar 

  120. 120.

    Baek JY, Han SH, Sung SH, Lee HE, Kim YM, Noh YH, Bae SH, Rhee SG, Chang TS (2012) Sulfiredoxin protein is critical for redox balance and survival of cells exposed to low steady-state levels of H2O2. J Biol Chem 287(1):81–89. https://doi.org/10.1074/jbc.M111.316711

    CAS  Article  PubMed  Google Scholar 

  121. 121.

    Lopert P, Day BJ, Patel M (2012) Thioredoxin reductase deficiency potentiates oxidative stress, mitochondrial dysfunction and cell death in dopaminergic cells. PLoS ONE 7(11):e50683. https://doi.org/10.1371/journal.pone.0050683

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  122. 122.

    Kudin AP, Augustynek B, Lehmann AK, Kovács R (1817) Kunz WS (2012) The contribution of thioredoxin-2 reductase and glutathione peroxidase to H2O2 detoxification of rat brain mitochondria. Biochimica et Biophysica Acta (BBA) 10:1901–1906. https://doi.org/10.1016/j.bbabio.2012.02.023

    CAS  Article  Google Scholar 

  123. 123.

    Fisher-Wellman KH, Gilliam LAA, Lin CT, Cathey BL, Lark DS, Darrell Neufer P (2013) Mitochondrial glutathione depletion reveals a novel role for the pyruvate dehydrogenase complex as a key H2O2-emitting source under conditions of nutrient overload. Free Radic Biol Med 65:1201–1208. https://doi.org/10.1016/j.freeradbiomed.2013.09.008

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Munro D, Banh S, Sotiri E, Tamanna N, Treberg JR (2016) The thioredoxin and glutathione-dependent H2O2 consumption pathways in muscle mitochondria: Involvement in H2O2 metabolism and consequence to H2O2 efflux assays. Free Radic Biol Med 96:334–346. https://doi.org/10.1016/j.freeradbiomed.2016.04.014

    CAS  Article  PubMed  Google Scholar 

  125. 125.

    Starkov AA, Andreyev AY, Zhang SF, Starkova NN, Korneeva M, Syromyatnikov M, Popov VN (2014) Scavenging of H2O2 by mouse brain mitochondria. J Bioenerg Biomembr 46(6):471–477. https://doi.org/10.1007/s10863-014-9581-9

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  126. 126.

    Hamilton RT, Walsh ME, Van Remmen H (2012) Mouse models of oxidative stress indicate a role for modulating healthy aging. J Clin Exp Pathol. https://doi.org/10.4172/2161-0681.s4-005

    Article  PubMed  PubMed Central  Google Scholar 

  127. 127.

    Cox AG, Winterbourn CC, Hampton MB (2009) Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling. Biochem J 425(2):313–325. https://doi.org/10.1042/bj20091541

    Article  PubMed  Google Scholar 

  128. 128.

    Gray E, Kemp K, Hares K, Redondo J, Rice C, Scolding N, Wilkins A (2014) Increased microglial catalase activity in multiple sclerosis grey matter. Brain Res 1559:55–64. https://doi.org/10.1016/j.brainres.2014.02.042

    CAS  Article  PubMed  Google Scholar 

  129. 129.

    Rohrdanz E, Schmuck G, Ohler S, Kahl R (2001) The influence of oxidative stress on catalase and MnSOD gene transcription in astrocytes. Brain Res 900(1):128–136. https://doi.org/10.1016/s0006-8993(01)02277-6

    CAS  Article  PubMed  Google Scholar 

  130. 130.

    Ho YS, Xiong Y, Ma W, Spector A, Ho DS (2004) Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem 279(31):32804–32812. https://doi.org/10.1074/jbc.M404800200

    CAS  Article  PubMed  Google Scholar 

  131. 131.

    Radi R, Turrens JF, Chang LY, Bush KM, Crapo JD, Freeman BA (1991) Detection of catalase in rat heart mitochondria. J Biol Chem 266(32):22028–22034

    CAS  PubMed  Google Scholar 

  132. 132.

    Salvi M, Battaglia V, Brunati AM, La Rocca N, Tibaldi E, Pietrangeli P, Marcocci L, Mondovì B, Rossi CA, Toninello A (2007) Catalase takes part in rat liver mitochondria oxidative stress defense. J Biol Chem 282(33):24407–24415. https://doi.org/10.1074/jbc.M701589200

    CAS  Article  PubMed  Google Scholar 

  133. 133.

    Munro D, Treberg JR (2017) A radical shift in perspective: mitochondria as regulators of reactive oxygen species. J Exp Biol 220(7):1170–1180. https://doi.org/10.1242/jeb.132142

    Article  PubMed  Google Scholar 

  134. 134.

    Dey S, Sidor A, O'Rourke B (2016) Compartment-specific control of reactive oxygen species scavenging by antioxidant pathway enzymes. J Biol Chem 291(21):11185–11197. https://doi.org/10.1074/jbc.M116.726968

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  135. 135.

    Ronchi JA, Francisco A, Passos LA, Figueira TR, Castilho RF (2016) The contribution of nicotinamide nucleotide transhydrogenase to peroxide detoxification is dependent on the respiratory state and counterbalanced by other sources of NADPH in liver mitochondria. J Biol Chem 291(38):20173–20187. https://doi.org/10.1074/jbc.M116.730473

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  136. 136.

    Santos LRB, Muller C, de Souza AH, Takahashi HK, Spegel P, Sweet IR, Chae H, Mulder H, Jonas JC (2017) NNT reverse mode of operation mediates glucose control of mitochondrial NADPH and glutathione redox state in mouse pancreatic beta-cells. Mol Metab 6(6):535–547. https://doi.org/10.1016/j.molmet.2017.04.004

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  137. 137.

    Rydstrom J (2006) Mitochondrial NADPH, transhydrogenase and disease. Biochim Biophys Acta 1757(5–6):721–726. https://doi.org/10.1016/j.bbabio.2006.03.010

    CAS  Article  PubMed  Google Scholar 

  138. 138.

    Montano SJ, Lu J, Gustafsson TN, Holmgren A (2014) Activity assays of mammalian thioredoxin and thioredoxin reductase: fluorescent disulfide substrates, mechanisms, and use with tissue samples. Anal Biochem 449:139–146. https://doi.org/10.1016/j.ab.2013.12.025

    CAS  Article  PubMed  Google Scholar 

  139. 139.

    Cheng Q, Antholine WE, Myers JM, Kalyanaraman B, Arner ES, Myers CR (2010) The selenium-independent inherent pro-oxidant NADPH oxidase activity of mammalian thioredoxin reductase and its selenium-dependent direct peroxidase activities. J Biol Chem 285(28):21708–21723. https://doi.org/10.1074/jbc.M110.117259

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  140. 140.

    Berkholz DS, Faber HR, Savvides SN, Karplus PA (2008) Catalytic cycle of human glutathione reductase near 1 A resolution. J Mol Biol 382(2):371–384. https://doi.org/10.1016/j.jmb.2008.06.083

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  141. 141.

    Kamerbeek NM, van Zwieten R, de Boer M, Morren G, Vuil H, Bannink N, Lincke C, Dolman KM, Becker K, Heiner Schirmer R, Gromer S, Roos D (2007) Molecular basis of glutathione reductase deficiency in human blood cells. Blood 109(8):3560–3566. https://doi.org/10.1182/blood-2006-08-042531

    CAS  Article  PubMed  Google Scholar 

  142. 142.

    Linster CL, Van Schaftingen E (2007) Vitamin C. Biosynthesis, recycling and degradation in mammals. FEBS J 274(1):1–22. https://doi.org/10.1111/j.1742-4658.2006.05607.x

    CAS  Article  PubMed  Google Scholar 

  143. 143.

    Bradshaw PC (2019) Cytoplasmic and mitochondrial NADPH-coupled redox systems in the regulation of aging. Nutrients 11(3):504. https://doi.org/10.3390/nu11030504

    CAS  Article  PubMed Central  Google Scholar 

  144. 144.

    Arroyo A, Kagan VE, Tyurin VA, Burgess JR, de Cabo R, Navas P, Villalba JM (2000) NADH and NADPH-dependent reduction of coenzyme Q at the plasma membrane. Antioxid Redox Signal 2(2):251–262. https://doi.org/10.1089/ars.2000.2.2-251

    CAS  Article  PubMed  Google Scholar 

  145. 145.

    Takahashi T, Okuno M, Okamoto T, Kishi T (2008) NADPH-dependent coenzyme Q reductase is the main enzyme responsible for the reduction of non-mitochondrial CoQ in cells. BioFactors (Oxford, England) 32(1–4):59–70

    CAS  Article  Google Scholar 

  146. 146.

    Heck DE, Shakarjian M, Kim HD, Laskin JD, Vetrano AM (2010) Mechanisms of oxidant generation by catalase. Ann N Y Acad Sci 1203:120–125. https://doi.org/10.1111/j.1749-6632.2010.05603.x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  147. 147.

    Holper L, Ben-Shachar D, Mann JJ (2019) Multivariate meta-analyses of mitochondrial complex I and IV in major depressive disorder, bipolar disorder, schizophrenia, Alzheimer disease, and Parkinson disease. Neuropsychopharmacology 44(5):837–849. https://doi.org/10.1038/s41386-018-0090-0

    CAS  Article  PubMed  Google Scholar 

  148. 148.

    Kim Y, Vadodaria KC, Lenkei Z, Kato T, Gage FH, Marchetto MC, Santos R (2019) Mitochondria, metabolism, and redox mechanisms in psychiatric disorders. Antioxid Redox Signal 31(4):275–317. https://doi.org/10.1089/ars.2018.7606

    CAS  Article  PubMed  Google Scholar 

  149. 149.

    Fang J, Holmgren A (2006) Inhibition of thioredoxin and thioredoxin reductase by 4-hydroxy-2-nonenal in vitro and in vivo. J Am Chem Soc 128(6):1879–1885. https://doi.org/10.1021/ja057358l

    CAS  Article  PubMed  Google Scholar 

  150. 150.

    Cruz-Tapias P, Agmon-Levin N, Israeli E, Anaya JM, Shoenfeld Y (2013) Autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA)–animal models as a proof of concept. Curr Med Chem 20(32):4030–4036

    CAS  Article  Google Scholar 

  151. 151.

    Garcia-Nogales P, Almeida A, Bolanos JP (2003) Peroxynitrite protects neurons against nitric oxide-mediated apoptosis. A key role for glucose-6-phosphate dehydrogenase activity in neuroprotection. J Biol Chem 278(2):864–874. https://doi.org/10.1074/jbc.M206835200

    CAS  Article  PubMed  Google Scholar 

  152. 152.

    Bayir H, Kagan VE, Clark RS, Janesko-Feldman K, Rafikov R, Huang Z, Zhang X, Vagni V, Billiar TR, Kochanek PM (2007) Neuronal NOS-mediated nitration and inactivation of manganese superoxide dismutase in brain after experimental and human brain injury. J Neurochem 101(1):168–181. https://doi.org/10.1111/j.1471-4159.2006.04353.x

    CAS  Article  PubMed  Google Scholar 

  153. 153.

    Isobe C, Abe T, Terayama Y (2009) Increase in the oxidized/total coenzyme Q-10 ratio in the cerebrospinal fluid of Alzheimer’s disease patients. Dement Geriatr Cogn Disord 28(5):434–439. https://doi.org/10.1159/000256209

    CAS  Article  Google Scholar 

  154. 154.

    Gomez-Diaz C, Rodriguez-Aguilera JC, Barroso MP, Villalba JM, Navarro F, Crane FL, Navas P (1997) Antioxidant ascorbate is stabilized by NADH-coenzyme Q10 reductase in the plasma membrane. J Bioenergy Biomembr 29(3):251–257

    CAS  Article  Google Scholar 

  155. 155.

    Bello RI, Kagan VE, Tyurin V, Navarro F, Alcain FJ, Villalba JM (2003) Regeneration of lipophilic antioxidants by NAD(P)H:quinone oxidoreductase 1. Protoplasma 221(1–2):129–135. https://doi.org/10.1007/s00709-002-0068-x

    CAS  Article  PubMed  Google Scholar 

  156. 156.

    Liu Q, Gao Y, Ci X (2019) Role of Nrf2 and its activators in respiratory diseases. Oxid Med Cell Longev 2019:17. https://doi.org/10.1155/2019/7090534

    CAS  Article  Google Scholar 

  157. 157.

    Wu YT, Wu SB, Lee WY, Wei YH (2010) Mitochondrial respiratory dysfunction-elicited oxidative stress and posttranslational protein modification in mitochondrial diseases. Ann N Y Acad Sci 1201:147–156. https://doi.org/10.1111/j.1749-6632.2010.05631.x

    CAS  Article  PubMed  Google Scholar 

  158. 158.

    Wang CH, Wu SB, Wu YT, Wei YH (2013) Oxidative stress response elicited by mitochondrial dysfunction: implication in the pathophysiology of aging. Exp Biol Med (Maywood, NJ) 238(5):450–460. https://doi.org/10.1177/1535370213493069

    CAS  Article  Google Scholar 

  159. 159.

    Ashrafi G, Schlehe JS, LaVoie MJ, Schwarz TL (2014) Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. J Cell Biol 206(5):655–670. https://doi.org/10.1083/jcb.201401070

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  160. 160.

    Kubli DA, Gustafsson ÅB (2012) Mitochondria and mitophagy: the yin and yang of cell death control. Circ Res 111(9):1208–1221. https://doi.org/10.1161/CIRCRESAHA.112.265819

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  161. 161.

    Zhang Q, Padayatti PS, Leung JH (2017) Proton-translocating nicotinamide nucleotide transhydrogenase: a structural perspective. Front Physiol 8:1089. https://doi.org/10.3389/fphys.2017.01089

    Article  PubMed  PubMed Central  Google Scholar 

  162. 162.

    Padayatti PS, Leung JH, Mahinthichaichan P, Tajkhorshid E, Ishchenko A, Cherezov V, Soltis SM, Jackson JB, Stout CD, Gennis RB, Zhang Q (2017) Critical role of water molecules in proton translocation by the membrane-bound transhydrogenase. Structure 25(7):1111–1119.e1113. https://doi.org/10.1016/j.str.2017.05.022

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  163. 163.

    Leung JH, Schurig-Briccio LA, Yamaguchi M, Moeller A, Speir JA, Gennis RB, Stout CD (2015) Structural biology. Division of labor in transhydrogenase by alternating proton translocation and hydride transfer. Science 347(6218):178–181. https://doi.org/10.1126/science.1260451

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  164. 164.

    Ho H-Y, Lin Y-T, Lin G, Wu P-R, Cheng M-L (2017) Nicotinamide nucleotide transhydrogenase (NNT) deficiency dysregulates mitochondrial retrograde signaling and impedes proliferation. Redox Biol 12:916–928. https://doi.org/10.1016/j.redox.2017.04.035

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  165. 165.

    Murphy Michael P (2015) Redox modulation by reversal of the mitochondrial nicotinamide nucleotide transhydrogenase. Cell Metab 22(3):363–365. https://doi.org/10.1016/j.cmet.2015.08.012

    CAS  Article  PubMed  Google Scholar 

  166. 166.

    Ronchi JA, Figueira TR, Ravagnani FG, Oliveira HC, Vercesi AE, Castilho RF (2013) A spontaneous mutation in the nicotinamide nucleotide transhydrogenase gene of C57BL/6J mice results in mitochondrial redox abnormalities. Free Radic Biol Med 63:446–456. https://doi.org/10.1016/j.freeradbiomed.2013.05.049

    CAS  Article  PubMed  Google Scholar 

  167. 167.

    Yin F, Sancheti H (1817) Cadenas E (2012) Silencing of nicotinamide nucleotide transhydrogenase impairs cellular redox homeostasis and energy metabolism in PC12 cells. Biochim Biophys Acta 3:401–409. https://doi.org/10.1016/j.bbabio.2011.12.004

    CAS  Article  Google Scholar 

  168. 168.

    Sheeran FL, Rydström J, Shakhparonov MI, Pestov NB, Pepe S (2010) Diminished NADPH transhydrogenase activity and mitochondrial redox regulation in human failing myocardium. Biochimica et Biophysica Acta (BBA) 1797(6):1138–1148. https://doi.org/10.1016/j.bbabio.2010.04.002

    CAS  Article  Google Scholar 

  169. 169.

    Francisco A, Ronchi JA, Navarro CDC, Figueira TR, Castilho RF (2018) Nicotinamide nucleotide transhydrogenase is required for brain mitochondrial redox balance under hampered energy substrate metabolism and high-fat diet. J Neurochem 147(5):663–677. https://doi.org/10.1111/jnc.14602

    CAS  Article  PubMed  Google Scholar 

  170. 170.

    Navarro CDC, Figueira TR, Francisco A, Dal'Bo GA, Ronchi JA, Rovani JC, Escanhoela CAF, Oliveira HCF, Castilho RF, Vercesi AE (2017) Redox imbalance due to the loss of mitochondrial NAD(P)-transhydrogenase markedly aggravates high fat diet-induced fatty liver disease in mice. Free Radic Biol Med 113:190–202. https://doi.org/10.1016/j.freeradbiomed.2017.09.026

    CAS  Article  PubMed  Google Scholar 

  171. 171.

    Nickel Alexander G, von Hardenberg A, Hohl M, Löffler Joachim R, Kohlhaas M, Becker J, Reil J-C, Kazakov A, Bonnekoh J, Stadelmaier M, Puhl S-L, Wagner M, Bogeski I, Cortassa S, Kappl R, Pasieka B, Lafontaine M, Lancaster C, Roy D, Blacker Thomas S, Hall Andrew R, Duchen Michael R, Kästner L, Lipp P, Zeller T, Müller C, Knopp A, Laufs U, Böhm M, Hoth M, Maack C (2015) Reversal of mitochondrial transhydrogenase causes oxidative stress in heart failure. Cell Metab 22(3):472–484. https://doi.org/10.1016/j.cmet.2015.07.008

    CAS  Article  PubMed  Google Scholar 

  172. 172.

    Chortis V, Taylor AE, Doig CL, Walsh MD, Meimaridou E, Jenkinson C, Rodriguez-Blanco G, Ronchi CL, Jafri A, Metherell LA, Hebenstreit D, Dunn WB, Arlt W, Foster PA (2018) Nicotinamide nucleotide transhydrogenase as a novel treatment target in adrenocortical carcinoma. Endocrinology 159(8):2836–2849. https://doi.org/10.1210/en.2018-00014

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  173. 173.

    Zhang R (2015) MNADK, a long-awaited human mitochondrion-localized NAD kinase. J Cell Physiol 230(8):1697–1701. https://doi.org/10.1002/jcp.24926

    CAS  Article  PubMed  Google Scholar 

  174. 174.

    Ohashi K, Kawai S, Murata K (2012) Identification and characterization of a human mitochondrial NAD kinase. Nat Commun 3:1248. https://doi.org/10.1038/ncomms2262

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  175. 175.

    Love NR, Pollak N, Dölle C, Niere M, Chen Y, Oliveri P, Amaya E, Patel S, Ziegler M (2015) NAD kinase controls animal NADP biosynthesis and is modulated via evolutionarily divergent calmodulin-dependent mechanisms. Proc Natl Acad Sci USA 112(5):1386–1391. https://doi.org/10.1073/pnas.1417290112

    CAS  Article  PubMed  Google Scholar 

  176. 176.

    Hoxhaj G, Ben-Sahra I, Lockwood SE, Timson RC, Byles V, Henning GT, Gao P, Selfors LM, Asara JM, Manning BD (2019) Direct stimulation of NADP+ synthesis through Akt-mediated phosphorylation of NAD kinase. Science 363(6431):1088–1092. https://doi.org/10.1126/science.aau3903

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  177. 177.

    Pollak N, Niere M, Ziegler M (2007) NAD kinase levels control the NADPH concentration in human cells. J Biol Chem 282(46):33562–33571. https://doi.org/10.1074/jbc.M704442200

    CAS  Article  PubMed  Google Scholar 

  178. 178.

    Houten SM, Denis S, Te Brinke H, Jongejan A, van Kampen AH, Bradley EJ, Baas F, Hennekam RC, Millington DS, Young SP, Frazier DM, Gucsavas-Calikoglu M, Wanders RJ (2014) Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. Hum Mol Genet 23(18):5009–5016. https://doi.org/10.1093/hmg/ddu218

    CAS  Article  PubMed  Google Scholar 

  179. 179.

    Tort F, Ugarteburu O, Torres MA, Garcia-Villoria J, Giros M, Ruiz A, Ribes A (2016) Lysine restriction and pyridoxal phosphate administration in a NADK2 patient. Pediatrics. https://doi.org/10.1542/peds.2015-4534

    Article  PubMed  Google Scholar 

  180. 180.

    Kawai S, Murata K (2008) Structure and function of NAD kinase and NADP phosphatase: key enzymes that regulate the intracellular balance of NAD(H) and NADP(H). Biosci Biotechnol Biochem 72(4):919–930. https://doi.org/10.1271/bbb.70738

    CAS  Article  PubMed  Google Scholar 

  181. 181.

    Magni G, Orsomando G, Raffaelli N (2006) Structural and functional properties of NAD kinase, a key enzyme in NADP biosynthesis. Mini Rev Med Chem 6(7):739–746

    CAS  Article  Google Scholar 

  182. 182.

    Grose JH, Joss L, Velick SF, Roth JR (2006) Evidence that feedback inhibition of NAD kinase controls responses to oxidative stress. Proc Natl Acad Sci USA 103(20):7601–7606. https://doi.org/10.1073/pnas.0602494103

    CAS  Article  PubMed  Google Scholar 

  183. 183.

    Ohashi K, Kawai S, Koshimizu M, Murata K (2011) NADPH regulates human NAD kinase, a NADP(+)-biosynthetic enzyme. Mol Cell Biochem 355(1–2):57–64. https://doi.org/10.1007/s11010-011-0838-x

    CAS  Article  PubMed  Google Scholar 

  184. 184.

    Petrelli R, Felczak K, Cappellacci L (2011) NMN/NaMN adenylyltransferase (NMNAT) and NAD kinase (NADK) inhibitors: chemistry and potential therapeutic applications. Curr Med Chem 18(13):1973–1992

    CAS  Article  Google Scholar 

  185. 185.

    Shi F, Li Y, Li Y, Wang X (2009) Molecular properties, functions, and potential applications of NAD kinases. Acta Biochim Biophys Sin 41(5):352–361. https://doi.org/10.1093/abbs/gmp029

    CAS  Article  PubMed  Google Scholar 

  186. 186.

    Revollo JR, Grimm AA, Imai S-I (2004) The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem 279(49):50754–50763. https://doi.org/10.1074/jbc.M408388200

    CAS  Article  PubMed  Google Scholar 

  187. 187.

    Jayaram HN, Kusumanchi P, Yalowitz JA (2011) NMNAT expression and its relation to NAD metabolism. Curr Med Chem 18(13):1962–1972. https://doi.org/10.2174/092986711795590138

    CAS  Article  PubMed  Google Scholar 

  188. 188.

    Pittelli M, Formentini L, Faraco G, Lapucci A, Rapizzi E, Cialdai F, Romano G, Moneti G, Moroni F, Chiarugi A (2010) Inhibition of nicotinamide phosphoribosyltransferase: cellular bioenergetics reveals a mitochondrial insensitive NAD pool. J Biol Chem 285(44):34106–34114. https://doi.org/10.1074/jbc.M110.136739

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  189. 189.

    Burgos ES (2011) NAMPT in regulated NAD biosynthesis and its pivotal role in human metabolism. Curr Med Chem 18(13):1947–1961. https://doi.org/10.2174/092986711795590101

    CAS  Article  PubMed  Google Scholar 

  190. 190.

    Burgos ES, Schramm VL (2008) Weak coupling of ATP hydrolysis to the chemical equilibrium of human nicotinamide phosphoribosyltransferase. Biochemistry 47(42):11086–11096. https://doi.org/10.1021/bi801198m

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  191. 191.

    Zhang LQ, Van Haandel L, Xiong M, Huang P, Heruth DP, Bi C, Gaedigk R, Jiang X, Li D-Y, Wyckoff G, Grigoryev DN, Gao L, Li L, Wu M, Leeder JS, Ye SQ (2017) Metabolic and molecular insights into an essential role of nicotinamide phosphoribosyltransferase. Cell Death Dis 8:e2705. https://doi.org/10.1038/cddis.2017.132

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  192. 192.

    Zhang LQ, Heruth DP, Ye SQ (2011) Nicotinamide phosphoribosyltransferase in human diseases. J Bioanal Biomed 3:13–25. https://doi.org/10.4172/1948-593X.1000038

    CAS  Article  PubMed  Google Scholar 

  193. 193.

    Abeti R, Duchen MR (2012) Activation of PARP by oxidative stress induced by beta-amyloid: implications for Alzheimer's disease. Neurochem Res 37(11):2589–2596. https://doi.org/10.1007/s11064-012-0895-x

    CAS  Article  PubMed  Google Scholar 

  194. 194.

    Smith AJ, Ball SS, Bowater RP, Wormstone IM (2016) PARP-1 inhibition influences the oxidative stress response of the human lens. Redox Biol 8:354–362. https://doi.org/10.1016/j.redox.2016.03.003

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  195. 195.

    Rodriguez-Vargas JM, Ruiz-Magana MJ, Ruiz-Ruiz C, Majuelos-Melguizo J, Peralta-Leal A, Rodriguez MI, Munoz-Gamez JA, de Almodovar MR, Siles E, Rivas AL, Jaattela M, Oliver FJ (2012) ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy. Cell Res 22(7):1181–1198. https://doi.org/10.1038/cr.2012.70

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  196. 196.

    Alano CC, Garnier P, Ying W, Higashi Y, Kauppinen TM, Swanson RA (2010) NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J Neurosci 30(8):2967–2978. https://doi.org/10.1523/JNEUROSCI.5552-09.2010

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  197. 197.

    Imai S-I (2009) Nicotinamide phosphoribosyltransferase (Nampt): a link between NAD biology, metabolism, and diseases. Curr Pharm Des 15(1):20–28. https://doi.org/10.2174/138161209787185814

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  198. 198.

    Zhang D, Hu X, Li J, Liu J, Baks-Te Bulte L, Wiersma M, Malik NU, van Marion DMS, Tolouee M, Hoogstra-Berends F, Lanters EAH, van Roon AM, de Vries AAF, Pijnappels DA, de Groot NMS, Henning RH, Brundel B (2019) DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD(+) depletion in experimental atrial fibrillation. Nat Commun 10(1):1307. https://doi.org/10.1038/s41467-019-09014-2

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  199. 199.

    Stein LR, Imai S-I (2012) The dynamic regulation of NAD metabolism in mitochondria. Trends Endocrinol Metab 23(9):420–428. https://doi.org/10.1016/j.tem.2012.06.005

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  200. 200.

    Hopp A-K, Grüter P, Hottiger MO (2019) Regulation of Glucose Metabolism by NAD(+) and ADP-Ribosylation. Cells 8(8):890. https://doi.org/10.3390/cells8080890

    CAS  Article  PubMed Central  Google Scholar 

  201. 201.

    Lewis CA, Parker SJ, Fiske BP, McCloskey D, Gui DY, Green CR, Vokes NI, Feist AM, Vander Heiden MG, Metallo CM (2014) Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Mol Cell 55(2):253–263. https://doi.org/10.1016/j.molcel.2014.05.008

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  202. 202.

    Hsieh J-Y, Shih W-T, Kuo Y-H, Liu G-Y, Hung H-C (2019) Functional roles of metabolic intermediates in regulating the human mitochondrial NAD(P)+-dependent malic enzyme. Sci Rep 9(1):9081. https://doi.org/10.1038/s41598-019-45282-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  203. 203.

    Yamada S, Kotake Y, Demizu Y, Kurihara M, Sekino Y, Kanda Y (2014) NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells. Sci Rep 4:5952–5952. https://doi.org/10.1038/srep05952

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  204. 204.

    Tsybovsky Y, Malakhau Y, Strickland KC, Krupenko SA (2013) The mechanism of discrimination between oxidized and reduced coenzyme in the aldehyde dehydrogenase domain of Aldh1l1. Chem Biol Interact 202(1–3):62–69. https://doi.org/10.1016/j.cbi.2012.12.015

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  205. 205.

    Singh S, Brocker C, Koppaka V, Chen Y, Jackson BC, Matsumoto A, Thompson DC, Vasiliou V (2013) Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress. Free Radical Biol Med 56:89–101. https://doi.org/10.1016/j.freeradbiomed.2012.11.010

    CAS  Article  Google Scholar 

  206. 206.

    Shin M, Bryant JD, Momb J, Appling DR (2014) Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues. J Biol Chem 289(22):15507–15517. https://doi.org/10.1074/jbc.M114.555573

    CAS  Article  PubMed  Google Scholar 

  207. 207.

    Tedeschi PM, Vazquez A, Kerrigan JE, Bertino JR (2015) Mitochondrial methylenetetrahydrofolate dehydrogenase (MTHFD2) overexpression is associated with tumor cell proliferation and is a novel target for drug development. Mol Cancer Res 13(10):1361–1366. https://doi.org/10.1158/1541-7786.mcr-15-0117

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  208. 208.

    Martínez-Reyes I, Chandel NS (2014) Mitochondrial one-carbon metabolism maintains redox balance during hypoxia. Cancer Discov 4(12):1371–1373. https://doi.org/10.1158/2159-8290.CD-14-1228

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  209. 209.

    Zheng Y, Lin TY, Lee G, Paddock MN, Momb J, Cheng Z, Li Q, Fei DL, Stein BD, Ramsamooj S, Zhang G, Blenis J, Cantley LC (2018) Mitochondrial one-carbon pathway supports cytosolic folate integrity in cancer cells. Cell 175(6):1546–1560.e1517. https://doi.org/10.1016/j.cell.2018.09.041

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  210. 210.

    Fan J, Ye J, Kamphorst JJ, Shlomi T, Thompson CB, Rabinowitz JD (2014) Quantitative flux analysis reveals folate-dependent NADPH production. Nature 510(7504):298–302. https://doi.org/10.1038/nature13236

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  211. 211.

    Zeng C, Aleshin AE, Hardie JB, Harrison RW, Fromm HJ (1996) ATP-binding site of human brain hexokinase as studied by molecular modeling and site-directed mutagenesis. Biochemistry 35(40):13157–13164. https://doi.org/10.1021/bi960750e

    CAS  Article  PubMed  Google Scholar 

  212. 212.

    Wilson JE (2003) Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 206(12):2049–2057. https://doi.org/10.1242/jeb.00241

    CAS  Article  PubMed  Google Scholar 

  213. 213.

    John S, Weiss JN, Ribalet B (2011) Subcellular localization of hexokinases I and II directs the metabolic fate of glucose. PLoS ONE 6(3):e17674. https://doi.org/10.1371/journal.pone.0017674

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  214. 214.

    Roberts DJ, Miyamoto S (2015) Hexokinase II integrates energy metabolism and cellular protection: akting on mitochondria and TORCing to autophagy. Cell Death Differ 22(2):248–257. https://doi.org/10.1038/cdd.2014.173

    CAS  Article  PubMed  Google Scholar 

  215. 215.

    Mailloux RJ, Jin X, Willmore WG (2013) Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions. Redox Biol 2:123–139. https://doi.org/10.1016/j.redox.2013.12.011

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  216. 216.

    Shi Q, Xu H, Kleinman WA, Gibson GE (2008) Novel functions of the α-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease. Biochimica et Biophysica Acta (BBA) 1782(4):229–238. https://doi.org/10.1016/j.bbadis.2007.12.008

    CAS  Article  Google Scholar 

  217. 217.

    Tretter L, Adam-Vizi V (2000) Inhibition of Krebs cycle enzymes by hydrogen peroxide: a key role of [alpha]-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress. J Neurosci 20(24):8972–8979

    CAS  Article  Google Scholar 

  218. 218.

    Hiller S, DeKroon R, Hamlett ED, Xu L, Osorio C, Robinette J, Winnik W, Simington S, Maeda N, Alzate O, Yi X (2016) Alpha-lipoic acid supplementation protects enzymes from damage by nitrosative and oxidative stress. Biochim Biophys Acta 1860:36–45. https://doi.org/10.1016/j.bbagen.2015.09.001

    CAS  Article  PubMed  Google Scholar 

  219. 219.

    Adam-Vizi V, Tretter L (2013) The role of mitochondrial dehydrogenases in the generation of oxidative stress. Neurochem Int 62(5):757–763. https://doi.org/10.1016/j.neuint.2013.01.012

    CAS  Article  PubMed  Google Scholar 

  220. 220.

    Wu N, Yang M, Gaur U, Xu H, Yao Y, Li D (2016) Alpha-ketoglutarate: physiological functions and applications. Biomol Ther (Seoul) 24(1):1–8. https://doi.org/10.4062/biomolther.2015.078

    CAS  Article  Google Scholar 

  221. 221.

    Tretter L, Adam-Vizi V (2005) Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philos Trans R Soc Lond B Biol Sci 360(1464):2335–2345. https://doi.org/10.1098/rstb.2005.1764

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  222. 222.

    Tortora V, Quijano C, Freeman B, Radi R, Castro L (2007) Mitochondrial aconitase reaction with nitric oxide, S-nitrosoglutathione, and peroxynitrite: mechanisms and relative contributions to aconitase inactivation. Free Radic Biol Med 42(7):1075–1088. https://doi.org/10.1016/j.freeradbiomed.2007.01.007

    CAS  Article  PubMed  Google Scholar 

  223. 223.

    Han D, Canali R, Garcia J, Aguilera R, Gallaher TK, Cadenas E (2005) Sites and mechanisms of aconitase inactivation by peroxynitrite: modulation by citrate and glutathione. Biochemistry 44(36):11986–11996. https://doi.org/10.1021/bi0509393

    CAS  Article  PubMed  Google Scholar 

  224. 224.

    Lushchak OV, Piroddi M, Galli F, Lushchak VI (2014) Aconitase post-translational modification as a key in linkage between Krebs cycle, iron homeostasis, redox signaling, and metabolism of reactive oxygen species. Redox Rep 19(1):8–15. https://doi.org/10.1179/1351000213y.0000000073

    CAS  Article  PubMed  Google Scholar 

  225. 225.

    Hurd TR, Collins Y, Abakumova I, Chouchani ET, Baranowski B, Fearnley IM, Prime TA, Murphy MP, James AM (2012) Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species. J Biol Chem 287(42):35153–35160. https://doi.org/10.1074/jbc.M112.400002

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  226. 226.

    Yang ES, Richter C, Chun JS, Huh TL, Kang SS, Park JW (2002) Inactivation of NADP(+)-dependent isocitrate dehydrogenase by nitric oxide. Free Radic Biol Med 33(7):927–937. https://doi.org/10.1016/s0891-5849(02)00981-4

    CAS  Article  PubMed  Google Scholar 

  227. 227.

    Lee JH, Yang ES, Park JW (2003) Inactivation of NADP+-dependent isocitrate dehydrogenase by peroxynitrite. Implications for cytotoxicity and alcohol-induced liver injury. J Biol Chem 278(51):51360–51371. https://doi.org/10.1074/jbc.M302332200

    CAS  Article  PubMed  Google Scholar 

  228. 228.

    Kil IS, Park JW (2005) Regulation of mitochondrial NADP+-dependent isocitrate dehydrogenase activity by glutathionylation. J Biol Chem 280(11):10846–10854. https://doi.org/10.1074/jbc.M411306200

    CAS  Article  PubMed  Google Scholar 

  229. 229.

    Jiang P, Du W, Mancuso A, Wellen KE, Yang X (2013) Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 493(7434):689–693. https://doi.org/10.1038/nature11776

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  230. 230.

    Chang Y-L, Gao H-W, Chiang C-P, Wang W-M, Huang S-M, Ku C-F, Liu G-Y, Hung H-C (2015) Human mitochondrial NAD(P)+–dependent malic enzyme participates in cutaneous melanoma progression and invasion. J Investig Dermatol 135(3):807–815. https://doi.org/10.1038/jid.2014.385

    CAS  Article  PubMed  Google Scholar 

  231. 231.

    Reisz JA, Wither MJ, Dzieciatkowska M, Nemkov T, Issaian A, Yoshida T, Dunham AJ, Hill RC, Hansen KC, D'Alessandro A (2016) Oxidative modifications of glyceraldehyde 3-phosphate dehydrogenase regulate metabolic reprogramming of stored red blood cells. Blood 128(12):e32–42. https://doi.org/10.1182/blood-2016-05-714816

    CAS  Article  PubMed  Google Scholar 

  232. 232.

    Hansen JM, Zhang H, Jones DP (2006) Differential oxidation of thioredoxin-1, thioredoxin-2, and glutathione by metal ions. Free Radical Biol Med 40(1):138–145. https://doi.org/10.1016/j.freeradbiomed.2005.09.023

    CAS  Article  Google Scholar 

  233. 233.

    Pias EK, Ekshyyan OY, Rhoads CA, Fuseler J, Harrison L, Aw TY (2003) Differential effects of superoxide dismutase isoform expression on hydroperoxide-induced apoptosis in PC-12 cells. J Biol Chem 278(15):13294–13301. https://doi.org/10.1074/jbc.M208670200

    CAS  Article  PubMed  Google Scholar 

  234. 234.

    Francescutti D, Baldwin J, Lee L, Mutus B (1996) Peroxynitrite modification of glutathione reductase: modeling studies and kinetic evidence suggest the modification of tyrosines at the glutathione disulfide binding site. Protein Eng 9(2):189–194

    CAS  Article  Google Scholar 

  235. 235.

    Savvides SN, Scheiwein M, Bohme CC, Arteel GE, Karplus PA, Becker K, Schirmer RH (2002) Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite. J Biol Chem 277(4):2779–2784. https://doi.org/10.1074/jbc.M108190200

    CAS  Article  PubMed  Google Scholar 

  236. 236.

    Circu ML, Stringer S, Rhoads CA, Moyer MP, Aw TY (2009) The role of GSH efflux in staurosporine-induced apoptosis in colonic epithelial cells. Biochem Pharmacol 77(1):76–85. https://doi.org/10.1016/j.bcp.2008.09.011

    CAS  Article  PubMed  Google Scholar 

  237. 237.

    Franco R, Cidlowski JA (2012) Glutathione efflux and cell death. Antioxid Redox Signal 17(12):1694–1713. https://doi.org/10.1089/ars.2012.4553

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  238. 238.

    Hammond CL, Madejczyk MS, Ballatori N (2004) Activation of plasma membrane reduced glutathione transport in death receptor apoptosis of HepG2 cells. Toxicol Appl Pharmacol 195(1):12–22. https://doi.org/10.1016/j.taap.2003.10.008

    CAS  Article  PubMed  Google Scholar 

  239. 239.

    Sodani K, Patel A, Kathawala RJ, Chen Z-S (2012) Multidrug resistance associated proteins in multidrug resistance. Chin J Cancer 31(2):58–72. https://doi.org/10.5732/cjc.011.10329

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  240. 240.

    Minich T, Riemer J, Schulz JB, Wielinga P, Wijnholds J, Dringen R (2006) The multidrug resistance protein 1 (Mrp1), but not Mrp5, mediates export of glutathione and glutathione disulfide from brain astrocytes. J Neurochem 97(2):373–384. https://doi.org/10.1111/j.1471-4159.2006.03737.x

    CAS  Article  PubMed  Google Scholar 

  241. 241.

    Hirrlinger J, Dringen R (2005) Multidrug resistance protein 1-mediated export of glutathione and glutathione disulfide from brain astrocytes. Methods Enzymol 400:395–409. https://doi.org/10.1016/s0076-6879(05)00023-6

    CAS  Article  PubMed  Google Scholar 

  242. 242.

    Ballatori N, Krance SM, Marchan R, Hammond CL (2009) Plasma membrane glutathione transporters and their roles in cell physiology and pathophysiology. Mol Aspects Med 30(1–2):13–28. https://doi.org/10.1016/j.mam.2008.08.004

    CAS  Article  PubMed  Google Scholar 

  243. 243.

    Hashemy SI, Holmgren A (2008) Regulation of the catalytic activity and structure of human thioredoxin 1 via oxidation and S-nitrosylation of cysteine residues. J Biol Chem 283(32):21890–21898. https://doi.org/10.1074/jbc.M801047200

    CAS  Article  PubMed  Google Scholar 

  244. 244.

    Rassaf T, Luedike P (2010) Between nitros(yl)ation and nitration: regulation of thioredoxin-1 in myocardial ischemia/reperfusion injury. J Mol Cell Cardiol 49(3):343–346. https://doi.org/10.1016/j.yjmcc.2010.06.001

    CAS  Article  PubMed  Google Scholar 

  245. 245.

    Yin T, Hou R, Liu S, Lau WB, Wang H, Tao L (2010) Nitrative inactivation of thioredoxin-1 increases vulnerability of diabetic hearts to ischemia/reperfusion injury. J Mol Cell Cardiol 49(3):354–361. https://doi.org/10.1016/j.yjmcc.2010.05.002

    CAS  Article  PubMed  Google Scholar 

  246. 246.

    Wang YT, Piyankarage SC, Williams DL, Thatcher GR (2014) Proteomic profiling of nitrosative stress: protein S-oxidation accompanies S-nitrosylation. ACS Chem Biol 9(3):821–830. https://doi.org/10.1021/cb400547u

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  247. 247.

    Du Y, Zhang H, Zhang X, Lu J, Holmgren A (2013) Thioredoxin 1 is inactivated due to oxidation induced by peroxiredoxin under oxidative stress and reactivated by the glutaredoxin system. J Biol Chem 288(45):32241–32247. https://doi.org/10.1074/jbc.M113.495150

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  248. 248.

    Tao L, Jiao X, Gao E, Lau WB, Yuan Y, Lopez B, Christopher T, RamachandraRao SP, Williams W, Southan G, Sharma K, Koch W, Ma XL (2006) Nitrative inactivation of thioredoxin-1 and its role in postischemic myocardial apoptosis. Circulation 114(13):1395–1402. https://doi.org/10.1161/CIRCULATIONAHA.106.625061

    CAS  Article  PubMed  Google Scholar 

  249. 249.

    Engelman R, Ziv T, Arner ESJ, Benhar M (2016) Inhibitory nitrosylation of mammalian thioredoxin reductase 1: molecular characterization and evidence for its functional role in cellular nitroso-redox imbalance. Free Radic Biol Med 97:375–385. https://doi.org/10.1016/j.freeradbiomed.2016.06.032

    CAS  Article  PubMed  Google Scholar 

  250. 250.

    Zhang X, Lu J, Ren X, Du Y, Zheng Y, Ioannou PV, Holmgren A (2015) Oxidation of structural cysteine residues in thioredoxin 1 by aromatic arsenicals enhances cancer cell cytotoxicity caused by the inhibition of thioredoxin reductase 1. Free Radic Biol Med 89:192–200. https://doi.org/10.1016/j.freeradbiomed.2015.07.010

    CAS  Article  PubMed  Google Scholar 

  251. 251.

    Biterova EI, Turanov AA, Gladyshev VN, Barycki JJ (2005) Crystal structures of oxidized and reduced mitochondrial thioredoxin reductase provide molecular details of the reaction mechanism. Proc Natl Acad Sci USA 102(42):15018–15023. https://doi.org/10.1073/pnas.0504218102

    CAS  Article  PubMed  Google Scholar 

  252. 252.

    Wang K, Zhang J, Wang X, Liu X, Zuo L, Bai K, Shang J, Ma L, Liu T, Wang L, Wang W, Ma X, Liu H (2013) Thioredoxin reductase was nitrated in the aging heart after myocardial ischemia/reperfusion. Rejuvenation Res 16(5):377–385. https://doi.org/10.1089/rej.2013.1437

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  253. 253.

    Morris G, Anderson G, Dean O, Berk M, Galecki P, Martin-Subero M (2014) The glutathione system: a new drug target in neuroimmune disorders. Mol Neurobiol 50:1059–1084

    CAS  Article  Google Scholar 

  254. 254.

    Cebula M, Schmidt EE, Arner ES (2015) TrxR1 as a potent regulator of the Nrf2-Keap1 response system. Antioxid Redox Signal 23(10):823–853. https://doi.org/10.1089/ars.2015.6378

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  255. 255.

    Schmidt EE (2015) Interplay between cytosolic disulfide reductase systems and the Nrf2/Keap1 pathway. Biochem Soc Trans 43(4):632–638. https://doi.org/10.1042/BST20150021

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  256. 256.

    Hansen JM, Watson WH, Jones DP (2004) Compartmentation of Nrf-2 redox control: regulation of cytoplasmic activation by glutathione and DNA binding by thioredoxin-1. Toxicol Sci 82(1):308–317. https://doi.org/10.1093/toxsci/kfh231

    CAS  Article  PubMed  Google Scholar 

  257. 257.

    Sueblinvong V, Mills ST, Neujahr DC, Go Y-M, Jones DP, Guidot DM (2016) Nuclear thioredoxin-1 overexpression attenuates alcohol-mediated Nrf2 signaling and lung fibrosis. Alcoholism 40(9):1846–1856. https://doi.org/10.1111/acer.13148

    CAS  Article  PubMed  Google Scholar 

  258. 258.

    Baird L, Dinkova-Kostova AT (2013) Diffusion dynamics of the Keap1-Cullin3 interaction in single live cells. Biochem Biophys Res Commun 433(1):58–65. https://doi.org/10.1016/j.bbrc.2013.02.065

    CAS  Article  PubMed  Google Scholar 

  259. 259.

    Marinho HS, Real C, Cyrne L, Soares H, Antunes F (2014) Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox Biol 2:535–562. https://doi.org/10.1016/j.redox.2014.02.006

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  260. 260.

    Covas G, Marinho HS, Cyrne L, Antunes F (2013) Activation of Nrf2 by H2O2: de novo synthesis versus nuclear translocation. Methods Enzymol 528:157–171. https://doi.org/10.1016/b978-0-12-405881-1.00009-4

    CAS  Article  PubMed  Google Scholar 

  261. 261.

    Raninga PV, Trapani GD, Tonissen KF (2014) Cross talk between two antioxidant Systems, thioredoxin and DJ-1: consequences for cancer. Oncoscience 1(1):95–110. https://doi.org/10.18632/oncoscience.12

    Article  PubMed  PubMed Central  Google Scholar 

  262. 262.

    Liu C, Chen Y, Kochevar IE, Jurkunas UV (2014) Decreased DJ-1 leads to impaired Nrf2-regulated antioxidant defense and increased UV-A-induced apoptosis in corneal endothelial cells. Invest Ophthalmol Vis Sci 55(9):5551–5560. https://doi.org/10.1167/iovs.14-14580

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  263. 263.

    Clements CM, McNally RS, Conti BJ, Mak TW, Ting JP-Y (2006) DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2. Proc Natl Acad Sci USA 103(41):15091–15096. https://doi.org/10.1073/pnas.0607260103

    CAS  Article  PubMed  Google Scholar 

  264. 264.

    Buhrke T, Voss L, Briese A, Stephanowitz H, Krause E, Braeuning A, Lampen A (2018) Oxidative inactivation of the endogenous antioxidant protein DJ-1 by the food contaminants 3-MCPD and 2-MCPD. Arch Toxicol 92(1):289–299. https://doi.org/10.1007/s00204-017-2027-5

    CAS  Article  PubMed  Google Scholar 

  265. 265.

    Wilson MA (2011) The role of cysteine oxidation in DJ-1 function and dysfunction. Antioxid Redox Signal 15(1):111–122. https://doi.org/10.1089/ars.2010.3481

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  266. 266.

    Durigon R, Wang Q, Ceh Pavia E, Grant CM, Lu H (2012) Cytosolic thioredoxin system facilitates the import of mitochondrial small Tim proteins. EMBO Rep 13(10):916–922. https://doi.org/10.1038/embor.2012.116

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  267. 267.

    Morgan B, Lu H (2008) Oxidative folding competes with mitochondrial import of the small Tim proteins. Biochem J 411(1):115–122. https://doi.org/10.1042/bj20071476

    CAS  Article  PubMed  Google Scholar 

  268. 268.

    Fukai T (2009) Mitochondrial thioredoxin: novel regulator for NADPH oxidase and angiotensin II-induced hypertension. Hypertension 54(2):224–225. https://doi.org/10.1161/HYPERTENSIONAHA.109.134403

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  269. 269.

    Chen B, Meng L, Shen T, Gong H, Qi R, Zhao Y, Sun J, Bao L, Zhao G (2017) Thioredoxin attenuates oxidized low-density lipoprotein induced oxidative stress in human umbilical vein endothelial cells by reducing NADPH oxidase activity. Biochem Biophys Res Commun 490(4):1326–1333. https://doi.org/10.1016/j.bbrc.2017.07.023

    CAS  Article  PubMed  Google Scholar 

  270. 270.

    Lu J, Holmgren A (2012) Thioredoxin system in cell death progression. Antioxid Redox Signal 17(12):1738–1747. https://doi.org/10.1089/ars.2012.4650

    CAS  Article  PubMed  Google Scholar 

  271. 271.

    Ostman B, Sjodin A, Michaelsson K, Byberg L (2012) Coenzyme Q10 supplementation and exercise-induced oxidative stress in humans. Nutrition (Burbank, Los Angeles County, Calif) 28(4):403–417. https://doi.org/10.1016/j.nut.2011.07.010

    CAS  Article  Google Scholar 

  272. 272.

    Nagase M, Yamamoto Y, Matsumoto N, Arai Y, Hirose N (2018) Increased oxidative stress and coenzyme Q10 deficiency in centenarians. J Clin Biochem Nutr 63(2):129–136. https://doi.org/10.3164/jcbn.17-124

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  273. 273.

    Kontush A, Reich A, Baum K, Spranger T, Finckh B, Kohlschutter A, Beisiegel U (1997) Plasma ubiquinol-10 is decreased in patients with hyperlipidaemia. Atherosclerosis 129(1):119–126. https://doi.org/10.1016/s0021-9150(96)06021-2

    CAS  Article  PubMed  Google Scholar 

  274. 274.

    Siemieniuk E, Skrzydlewska E (2005) Coenzyme Q10: its biosynthesis and biological significance in animal organisms and in humans. Postepy Hig Med Dosw(Online) 59:150–159

    Google Scholar 

  275. 275.

    Katsyuba E, Mottis A, Zietak M, De Franco F, van der Velpen V, Gariani K, Ryu D, Cialabrini L, Matilainen O, Liscio P, Giacchè N, Stokar-Regenscheit N, Legouis D, de Seigneux S, Ivanisevic J, Raffaelli N, Schoonjans K, Pellicciari R, Auwerx J (2018) De novo NAD+ synthesis enhances mitochondrial function and improves health. Nature 563(7731):354–359. https://doi.org/10.1038/s41586-018-0645-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  276. 276.

    Lee CF, Caudal A, Abell L, Nagana Gowda GA, Tian R (2019) Targeting NAD+ metabolism as interventions for mitochondrial disease. Sci Rep 9(1):3073. https://doi.org/10.1038/s41598-019-39419-4

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  277. 277.

    Yang Y (1864) (2016) NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy. Biochim Biophys Acta 12:1787–1800. https://doi.org/10.1016/j.bbapap.2016.06.014

    CAS  Article  Google Scholar 

  278. 278.

    Poljsak B, Milisav I (2016) NAD+ as the link between oxidative stress, inflammation, caloric restriction, exercise, DNA repair, longevity, and health span. Rejuvenation Res 19(5):406–415. https://doi.org/10.1089/rej.2015.1767

    CAS  Article  PubMed  Google Scholar 

  279. 279.

    Parodi-Rullán RM, Chapa-Dubocq XR, Javadov S (2018) Acetylation of mitochondrial proteins in the heart: the role of SIRT3. Front Physiol. https://doi.org/10.3389/fphys.2018.01094

    Article  PubMed  PubMed Central  Google Scholar 

  280. 280.

    Tyagi A, Nguyen CU, Chong T, Michel CR, Fritz KS, Reisdorph N, Knaub L, Reusch JEB, Pugazhenthi S (2018) SIRT3 deficiency-induced mitochondrial dysfunction and inflammasome formation in the brain. Sci Rep 8(1):17547. https://doi.org/10.1038/s41598-018-35890-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  281. 281.

    Kim HS, Patel K, Muldoon-Jacobs K, Bisht KS, Aykin-Burns N, Pennington JD, van der Meer R, Nguyen P, Savage J, Owens KM, Vassilopoulos A, Ozden O, Park SH, Singh KK, Abdulkadir SA, Spitz DR, Deng CX, Gius D (2010) SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 17(1):41–52. https://doi.org/10.1016/j.ccr.2009.11.023

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  282. 282.

    Ahn B-H, Kim H-S, Song S, Lee IH, Liu J, Vassilopoulos A, Deng C-X, Finkel T (2008) A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci USA 105(38):14447–14452. https://doi.org/10.1073/pnas.0803790105

    Article  PubMed  Google Scholar 

  283. 283.

    Vassilopoulos A, Pennington JD, Andresson T, Rees DM, Bosley AD, Fearnley IM, Ham A, Flynn CR, Hill S, Rose KL, Kim HS, Deng CX, Walker JE, Gius D (2014) SIRT3 deacetylates ATP synthase F1 complex proteins in response to nutrient- and exercise-induced stress. Antioxid Redox Signal 21(4):551–564. https://doi.org/10.1089/ars.2013.5420

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  284. 284.

    Law IK, Liu L, Xu A, Lam KS, Vanhoutte PM, Che CM, Leung PT, Wang Y (2009) Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the anti-aging and metabolic effects of sirtuins. Proteomics 9(9):2444–2456. https://doi.org/10.1002/pmic.200800738

    CAS  Article  PubMed  Google Scholar 

  285. 285.

    Wu YT, Lee HC, Liao CC (4977bp) Wei YH (2013) Regulation of mitochondrial F(o)F(1)ATPase activity by Sirt3-catalyzed deacetylation and its deficiency in human cells harboring 4977bp deletion of mitochondrial DNA. Biochim Biophys Acta 1:216–227. https://doi.org/10.1016/j.bbadis.2012.10.002

    CAS  Article  Google Scholar 

  286. 286.

    Rahman M, Nirala NK, Singh A, Zhu LJ, Taguchi K, Bamba T, Fukusaki E, Shaw LM, Lambright DG, Acharya JK, Acharya UR (2014) Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase beta and regulates complex V activity. J Cell Biol 206(2):289–305. https://doi.org/10.1083/jcb.201404118

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  287. 287.

    Finley LW, Haas W, Desquiret-Dumas V, Wallace DC, Procaccio V, Gygi SP, Haigis MC (2011) Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity. PLoS ONE 6(8):e23295. https://doi.org/10.1371/journal.pone.0023295

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  288. 288.

    Novgorodov SA, Riley CL, Keffler JA, Yu J, Kindy MS, Macklin WB, Lombard DB, Gudz TI (2016) SIRT3 deacetylates ceramide synthases: implications for mitochondrial dysfunction and brain injury. J Biol Chem 291(4):1957–1973. https://doi.org/10.1074/jbc.M115.668228

    CAS  Article  PubMed  Google Scholar 

  289. 289.

    Kendrick AA, Choudhury M, Rahman SM, McCurdy CE, Friederich M, Van Hove JL, Watson PA, Birdsey N, Bao J, Gius D, Sack MN, Jing E, Kahn CR, Friedman JE, Jonscher KR (2011) Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. Biochem J 433(3):505–514. https://doi.org/10.1042/bj20100791

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  290. 290.

    Traba J, Geiger SS, Kwarteng-Siaw M, Han K, Ra OH, Siegel RM, Gius D, Sack MN (2017) Prolonged fasting suppresses mitochondrial NLRP3 inflammasome assembly and activation via SIRT3-mediated activation of superoxide dismutase 2. J Biol Chem 292(29):12153–12164. https://doi.org/10.1074/jbc.M117.791715

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  291. 291.

    Geng K, Fu N, Yang X, Xia W (2018) Adjudin delays cellular senescence through Sirt3mediated attenuation of ROS production. Int J Mol Med 42(6):3522–3529. https://doi.org/10.3892/ijmm.2018.3917

    CAS  Article  PubMed  Google Scholar 

  292. 292.

    Qiao A, Wang K, Yuan Y, Guan Y, Ren X, Li L, Chen X, Li F, Chen AF, Zhou J, Yang J-M, Cheng Y (2016) Sirt3-mediated mitophagy protects tumor cells against apoptosis under hypoxia. Oncotarget 7(28):43390–43400. https://doi.org/10.18632/oncotarget.9717

    Article  PubMed  PubMed Central  Google Scholar 

  293. 293.

    Morris G, Puri BK, Walder K, Berk M, Stubbs B, Maes M, Carvalho AF (2018) The endoplasmic reticulum stress response in neuroprogressive diseases: emerging pathophysiological role and translational implications. Mol Neurobiol 55(12):8765–8787. https://doi.org/10.1007/s12035-018-1028-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  294. 294.

    Fan P, Xie XH, Chen CH, Peng X, Zhang P, Yang C, Wang YT (2019) Molecular regulation mechanisms and interactions between reactive oxygen species and mitophagy. DNA Cell Biol 38(1):10–22. https://doi.org/10.1089/dna.2018.4348

    CAS  Article  PubMed  Google Scholar 

  295. 295.

    Palacios OM, Carmona JJ, Michan S, Chen KY, Manabe Y, Ward JL 3rd, Goodyear LJ, Tong Q (2009) Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging 1(9):771–783. https://doi.org/10.18632/aging.100075

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  296. 296.

    Fu J, Jin J, Cichewicz RH, Hageman SA, Ellis TK, Xiang L, Peng Q, Jiang M, Arbez N, Hotaling K, Ross CA, Duan W (2012) trans-(-)-epsilon-Viniferin increases mitochondrial sirtuin 3 (SIRT3), activates AMP-activated protein kinase (AMPK), and protects cells in models of Huntington disease. J Biol Chem 287(29):24460–24472. https://doi.org/10.1074/jbc.M112.382226

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  297. 297.

    Rabinovitch RC, Samborska B, Faubert B, Ma EH, Gravel S-P, Andrzejewski S, Raissi TC, Pause A, St.-Pierre J, Jones RG (2017) AMPK maintains cellular metabolic homeostasis through regulation of mitochondrial reactive oxygen species. Cell Rep 21(1):1–9. https://doi.org/10.1016/j.celrep.2017.09.026

    CAS  Article  PubMed  Google Scholar 

  298. 298.

    Hinchy EC, Gruszczyk AV, Willows R, Navaratnam N, Hall AR, Bates G, Bright TP, Krieg T, Carling D, Murphy MP (2018) Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly. J Biol Chem. https://doi.org/10.1074/jbc.RA118.002579

    Article  PubMed  PubMed Central  Google Scholar 

  299. 299.

    Balteau M, Steenbergen AV, Timmermans AD, Dessy C, Behets-Wydemans G, Tajeddine N, Castanares-Zapatero D, Gilon P, Vanoverschelde J-L, Horman S, Hue L, Bertrand L, Beauloye C (2014) AMPK activation by glucagon-like peptide-1 prevents NADPH oxidase activation induced by hyperglycemia in adult cardiomyocytes. Am J Physiol Heart Circ Physiol 307(8):H1120–H1133. https://doi.org/10.1152/ajpheart.00210.2014

    CAS  Article  PubMed  Google Scholar 

  300. 300.

    Wu S-B, Wei Y-H (2012) AMPK-mediated increase of glycolysis as an adaptive response to oxidative stress in human cells: implication of the cell survival in mitochondrial diseases. Biochimica et Biophysica Acta (BBA) 1822(2):233–247. https://doi.org/10.1016/j.bbadis.2011.09.014

    CAS  Article  Google Scholar 

  301. 301.

    Jeon SM, Chandel NS, Hay N (2012) AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 485(7400):661–665. https://doi.org/10.1038/nature11066

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  302. 302.

    Liu TF, Vachharajani VT, Yoza BK, McCall CE (2012) NAD+-dependent sirtuin 1 and 6 proteins coordinate a switch from glucose to fatty acid oxidation during the acute inflammatory response. J Biol Chem 287(31):25758–25769. https://doi.org/10.1074/jbc.M112.362343

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  303. 303.

    Sim WC, Kim DG, Lee W, Sim H, Choi YJ, Lee BH (2019) Activation of SIRT1 by L-serine increases fatty acid oxidation and reverses insulin resistance in C2C12 myotubes (l-serine activates SIRT1 in C2C12 myotubes). Cell Biol Toxicol. https://doi.org/10.1007/s10565-019-09463-x

    Article  PubMed  Google Scholar 

  304. 304.

    Qu Q, Zeng F, Liu X, Wang QJ, Deng F (2016) Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer. Cell Death Dis 7:e2226. https://doi.org/10.1038/cddis.2016.132

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  305. 305.

    Morris G, Maes M, Berk M, Puri BK (2019) Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop? Metab Brain Dis 34(2):385–415. https://doi.org/10.1007/s11011-019-0388-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  306. 306.

    Jang SY, Kang HT, Hwang ES (2012) Nicotinamide-induced mitophagy: event mediated by high NAD+/NADH ratio and SIRT1 protein activation. J Biol Chem 287(23):19304–19314. https://doi.org/10.1074/jbc.M112.363747

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  307. 307.

    Xu J, Jackson CW, Khoury N, Escobar I, Perez-Pinzon MA (2018) Brain SIRT1 mediates metabolic homeostasis and neuroprotection. Front Endocrinol. https://doi.org/10.3389/fendo.2018.00702

    Article  Google Scholar 

  308. 308.

    Olmos Y, Sanchez-Gomez FJ, Wild B, Garcia-Quintans N, Cabezudo S, Lamas S, Monsalve M (2013) SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1alpha complex. Antioxid Redox Signal 19(13):1507–1521. https://doi.org/10.1089/ars.2012.4713

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  309. 309.

    St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, Handschin C, Zheng K, Lin J, Yang W, Simon DK, Bachoo R, Spiegelman BM (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127(2):397–408. https://doi.org/10.1016/j.cell.2006.09.024

    CAS  Article  PubMed  Google Scholar 

  310. 310.

    Aquilano K, Baldelli S, Pagliei B, Cannata SM, Rotilio G, Ciriolo MR (2013) p53 orchestrates the PGC-1α-mediated antioxidant response upon mild redox and metabolic imbalance. Antioxid Redox Signal 18(4):386–399. https://doi.org/10.1089/ars.2012.4615

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  311. 311.

    Tsunemi T, Ashe TD, Morrison BE, Soriano KR, Au J, Roque RAV, Lazarowski ER, Damian VA, Masliah E, La Spada AR (2012) PGC-1α rescues Huntington’s disease proteotoxicity by preventing oxidative stress and promoting TFEB function. Sci Transl Med 4(142):142ra197. https://doi.org/10.1126/scitranslmed.3003799

    CAS  Article  Google Scholar 

  312. 312.

    Baldelli S, Aquilano K, Ciriolo MR (2014) PGC-1α buffers ROS-mediated removal of mitochondria during myogenesis. Cell Death Dis 5(11):e1515–e1515. https://doi.org/10.1038/cddis.2014.458

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  313. 313.

    Miller VJ, Villamena FA, Volek JS (2018) Nutritional ketosis and mitohormesis: potential implications for mitochondrial function and human health. J Nutr Metab 2018:5157645–5157645. https://doi.org/10.1155/2018/5157645

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  314. 314.

    Ploumi C, Daskalaki I, Tavernarakis N (2017) Mitochondrial biogenesis and clearance: a balancing act. FEBS J 284(2):183–195. https://doi.org/10.1111/febs.13820

    CAS  Article  PubMed  Google Scholar 

  315. 315.

    Scarpulla RC (2011) Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta 1813(7):1269–1278. https://doi.org/10.1016/j.bbamcr.2010.09.019

    CAS  Article  PubMed  Google Scholar 

  316. 316.

    Zhu J, Wang KZQ, Chu CT (2013) After the banquet: mitochondrial biogenesis, mitophagy, and cell survival. Autophagy 9(11):1663–1676. https://doi.org/10.4161/auto.24135

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  317. 317.

    Abid H, Cartier D, Hamieh A, Francois-Bellan AM, Bucharles C, Pothion H, Manecka DL, Leprince J, Adriouch S, Boyer O, Anouar Y, Lihrmann I (2019) AMPK activation of PGC-1alpha/NRF-1-dependent SELENOT gene transcription promotes PACAP-induced neuroendocrine cell differentiation through tolerance to oxidative stress. Mol Neurobiol 56(6):4086–4101. https://doi.org/10.1007/s12035-018-1352-x

    CAS  Article  PubMed  Google Scholar 

  318. 318.

    Yu L, Yang SJ (2010) AMP-activated protein kinase mediates activity-dependent regulation of peroxisome proliferator-activated receptor gamma coactivator-1alpha and nuclear respiratory factor 1 expression in rat visual cortical neurons. Neuroscience 169(1):23–38. https://doi.org/10.1016/j.neuroscience.2010.04.063

    CAS  Article  PubMed  Google Scholar 

  319. 319.

    Barchiesi A, Vascotto C (2019) Transcription, processing, and decay of mitochondrial RNA in health and disease. Int J Mol Sci 20(9):2221. https://doi.org/10.3390/ijms20092221

    CAS  Article  PubMed Central  Google Scholar 

  320. 320.

    Aquilano K, Baldelli S, Pagliei B, Ciriolo M (2013) Extranuclear localization of SIRT1 and PGC-1: an insight into possible roles in diseases associated with mitochondrial dysfunction. Curr Mol Med 13(1):140–154. https://doi.org/10.2174/156652413804486241

    CAS  Article  PubMed  Google Scholar 

  321. 321.

    Pagliei B, Aquilano K, Baldelli S, Ciriolo MR (2013) Garlic-derived diallyl disulfide modulates peroxisome proliferator activated receptor gamma co-activator 1 alpha in neuroblastoma cells. Biochem Pharmacol 85(3):335–344. https://doi.org/10.1016/j.bcp.2012.11.007

    CAS  Article  PubMed  Google Scholar 

  322. 322.

    Aquilano K, Vigilanza P, Baldelli S, Pagliei B, Rotilio G, Ciriolo MR (2010) Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and sirtuin 1 (SIRT1) reside in mitochondria: possible direct function in mitochondrial biogenesis. J Biol Chem 285(28):21590–21599. https://doi.org/10.1074/jbc.M109.070169

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  323. 323.

    Austin S, St-Pierre J (2012) PGC1α and mitochondrial metabolism – emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci 125(21):4963–4971. https://doi.org/10.1242/jcs.113662

    CAS  Article  PubMed  Google Scholar 

  324. 324.

    Austin S, Klimcakova E, St-Pierre J (2011) Impact of PGC-1alpha on the topology and rate of superoxide production by the mitochondrial electron transport chain. Free Radic Biol Med 51(12):2243–2248. https://doi.org/10.1016/j.freeradbiomed.2011.08.036

    CAS  Article  PubMed  Google Scholar 

  325. 325.

    Hoeks J, Arany Z, Phielix E, Moonen-Kornips E, Hesselink MK, Schrauwen P (2012) Enhanced lipid-but not carbohydrate-supported mitochondrial respiration in skeletal muscle of PGC-1alpha overexpressing mice. J Cell Physiol 227(3):1026–1033. https://doi.org/10.1002/jcp.22812

    CAS  Article  PubMed  Google Scholar 

  326. 326.

    Finkel T (2006) Cell biology: a clean energy programme. Nature 444(7116):151–152. https://doi.org/10.1038/444151a

    CAS  Article  PubMed  Google Scholar 

  327. 327.

    Kukat C, Davies KM, Wurm CA, Spåhr H, Bonekamp NA, Kühl I, Joos F, Polosa PL, Park CB, Posse V, Falkenberg M, Jakobs S, Kühlbrandt W, Larsson N-G (2015) Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid. Proc Natl Acad Sci USA 112(36):11288–11293. https://doi.org/10.1073/pnas.1512131112

    CAS  Article  PubMed  Google Scholar 

  328. 328.

    Picca A, Lezza AM (2015) Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions: useful insights from aging and calorie restriction studies. Mitochondrion 25:67–75. https://doi.org/10.1016/j.mito.2015.10.001

    CAS  Article  PubMed  Google Scholar 

  329. 329.

    Olmos Y, Valle I, Borniquel S, Tierrez A, Soria E, Lamas S, Monsalve M (2009) Mutual dependence of Foxo3a and PGC-1alpha in the induction of oxidative stress genes. J Biol Chem 284(21):14476–14484. https://doi.org/10.1074/jbc.M807397200

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  330. 330.

    Klotz L-O, Sánchez-Ramos C, Prieto-Arroyo I, Urbánek P, Steinbrenner H, Monsalve M (2015) Redox regulation of FoxO transcription factors. Redox Biol 6:51–72. https://doi.org/10.1016/j.redox.2015.06.019

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  331. 331.

    Valle I, Álvarez-Barrientos A, Arza E, Lamas S, Monsalve M (2005) PGC-1α regulates the mitochondrial antioxidant defense system in vascular endothelial cells. Cardiovasc Res 66(3):562–573. https://doi.org/10.1016/j.cardiores.2005.01.026

    CAS  Article  PubMed  Google Scholar 

  332. 332.

    Wang Y, Zhou Y, Graves DT (2014) FOXO transcription factors: their clinical significance and regulation. Biomed Res Int 2014:13. https://doi.org/10.1155/2014/925350

    Article  Google Scholar 

  333. 333.

    Yun H, Park S, Kim M-J, Yang WK, Im DU, Yang KR, Hong J, Choe W, Kang I, Kim SS, Ha J (2014) AMP-activated protein kinase mediates the antioxidant effects of resveratrol through regulation of the transcription factor FoxO1. FEBS J 281(19):4421–4438. https://doi.org/10.1111/febs.12949

    CAS  Article  PubMed  Google Scholar 

  334. 334.

    Zhao X, Petursson F, Viollet B, Lotz M, Terkeltaub R, Liu-Bryan R (2014) Peroxisome proliferator-activated receptor gamma coactivator 1alpha and FoxO3A mediate chondroprotection by AMP-activated protein kinase. Arthritis Rheumatol (Hoboken, NJ) 66(11):3073–3082. https://doi.org/10.1002/art.38791

    CAS  Article  Google Scholar 

  335. 335.

    Peserico A, Chiacchiera F, Grossi V, Matrone A, Latorre D, Simonatto M, Fusella A, Ryall JG, Finley LW, Haigis MC, Villani G, Puri PL, Sartorelli V, Simone C (2013) A novel AMPK-dependent FoxO3A-SIRT3 intramitochondrial complex sensing glucose levels. Cell Mol Life Sci 70(11):2015–2029. https://doi.org/10.1007/s00018-012-1244-6

    CAS  Article  PubMed  Google Scholar 

  336. 336.

    Webb AE, Brunet A (2014) FOXO transcription factors: key regulators of cellular quality control. Trends Biochem Sci 39(4):159–169. https://doi.org/10.1016/j.tibs.2014.02.003

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  337. 337.

    Palikaras K, Tavernarakis N (2014) Mitochondrial homeostasis: the interplay between mitophagy and mitochondrial biogenesis. Exp Gerontol 56:182–188. https://doi.org/10.1016/j.exger.2014.01.021

    CAS  Article  PubMed  Google Scholar 

  338. 338.

    Morris G, Berk M (2016) The putative use of lithium in Alzheimer's disease. Curr Alzheimer Res 13(8):853–861

    CAS  Article  Google Scholar 

  339. 339.

    Audesse AJ, Dhakal S, Hassell LA, Gardell Z, Nemtsova Y, Webb AE (2019) FOXO3 directly regulates an autophagy network to functionally regulate proteostasis in adult neural stem cells. PLoS Genet 15(4):e1008097. https://doi.org/10.1371/journal.pgen.1008097

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  340. 340.

    Mei Y, Zhang Y, Yamamoto K, Xie W, Mak TW, You H (2009) FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation. Proc Natl Acad Sci USA 106(13):5153–5158. https://doi.org/10.1073/pnas.0901104106

    Article  PubMed  Google Scholar 

  341. 341.

    Tan S, Wong E (2017) Mitophagy transcriptome: mechanistic insights into polyphenol-mediated mitophagy. Oxid Med Cell Longev 2017:9028435–9028435. https://doi.org/10.1155/2017/9028435

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  342. 342.

    Obsil T, Obsilova V (2011) Structural basis for DNA recognition by FOXO proteins. Biochimica et Biophysica Acta (BBA) 1813(11):1946–1953. https://doi.org/10.1016/j.bbamcr.2010.11.025

    CAS  Article  Google Scholar 

  343. 343.

    Tang BL (2016) Sirt1 and the mitochondria. Mol Cells 39(2):87–95. https://doi.org/10.14348/molcells.2016.2318

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  344. 344.

    Li P, Liu Y, Burns N, Zhao K-S, Song R (2017) SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells. Int J Mol Med 39(5):1127–1136. https://doi.org/10.3892/ijmm.2017.2932

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  345. 345.

    Ma S, Zhao Y, Sun J, Mu P, Deng Y (2018) miR449a/SIRT1/PGC-1α is necessary for mitochondrial biogenesis induced by T-2 toxin. Front Pharmacol. https://doi.org/10.3389/fphar.2017.00954

    Article  PubMed  PubMed Central  Google Scholar 

  346. 346.

    Das S, Mitrovsky G, Vasanthi HR, Das DK (2014) Antiaging properties of a grape-derived antioxidant are regulated by mitochondrial balance of fusion and fission leading to mitophagy triggered by a signaling network of Sirt1-Sirt3-Foxo3-PINK1-PARKIN. Oxid Med Cell Longev 2014:13. https://doi.org/10.1155/2014/345105

    CAS  Article  Google Scholar 

  347. 347.

    Papa L, Germain D (2014) SirT3 regulates the mitochondrial unfolded protein response. Mol Cell Biol 34(4):699–710. https://doi.org/10.1128/mcb.01337-13

    Article  PubMed  PubMed Central  Google Scholar 

  348. 348.

    Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM, Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331(6016):456–461. https://doi.org/10.1126/science.1196371

    CAS  Article  PubMed  Google Scholar 

  349. 349.

    Lee Y, Stevens DA, Kang SU, Jiang H, Lee YI, Ko HS, Scarffe LA, Umanah GE, Kang H, Ham S, Kam TI, Allen K, Brahmachari S, Kim JW, Neifert S, Yun SP, Fiesel FC, Springer W, Dawson VL, Shin JH, Dawson TM (2017) PINK1 primes Parkin-mediated ubiquitination of PARIS in dopaminergic neuronal survival. Cell Rep 18(4):918–932. https://doi.org/10.1016/j.celrep.2016.12.090

    CAS  Article  PubMed  PubMed Central