Advertisement

Role of Mitochondria in Neurodegenerative Diseases: The Dark Side of the “Energy Factory”

  • Sónia C. CorreiaEmail author
  • Paula I. MoreiraEmail author
Chapter

Abstract

Neurodegenerative disease is an umbrella term for a range of pathological conditions primarily characterized by the progressive dysfunction and loss of selective neuronal populations. Bereft of cure and effective disease-modifying therapies, why and how this selective neuronal loss occurs in neurodegenerative diseases remain as the most intriguing and still unsolved questions in the field. Despite this limited knowledge regarding the trigger(s) underlying the different neurodegenerative phenotypes, during the last decades, mitochondrial dysfunction emerged as a common pathological feature being considered a “convergence point” for neurodegeneration. This is not surprising taking into account that neurons are post-mitotic cells with a complex architecture, long lifespan, and energetic requirements that fluctuate in time and space making them particularly reliant on a functional and dynamic mitochondrial network. Within this scenario, the present chapter provides an overview on the role of mitochondrial pathobiology in Alzheimer, Parkinson and Huntington diseases, the most prevalent neurodegenerative diseases. A more comprehensive view on the fundamental role of mitochondrial (mal)function during the pathological course of the abovementioned diseases may offer a new therapeutic window of opportunity to tackle the neurodegenerative phenotypes by bolstering mitochondrial health.

Keywords

Alzheimer disease Huntington disease Mitochondrial bioenergetics and dynamics Neurodegeneration Parkinson disease 

References

  1. Ali SF, David SN, Newport GD, Cadet JL, Slikker W Jr (1994) MPTP-induced oxidative stress and neurotoxicity are age-dependent: evidence from measures of reactive oxygen species and striatal dopamine levels. Synapse 18(1):27–34.  https://doi.org/10.1002/syn.890180105 PubMedCrossRefGoogle Scholar
  2. Atamna H (2006) Heme binding to Amyloid-beta peptide: mechanistic role in Alzheimer's disease. J Alzheimers Disease 10(2–3):255–266CrossRefGoogle Scholar
  3. Atamna H, Frey WH 2nd (2004) A role for heme in Alzheimer's disease: heme binds amyloid beta and has altered metabolism. Proc Natl Acad Sci U S A 101(30):11153–11158.  https://doi.org/10.1073/pnas.0404349101 PubMedPubMedCentralCrossRefGoogle Scholar
  4. Autere J, Moilanen JS, Finnila S, Soininen H, Mannermaa A, Hartikainen P, Hallikainen M, Majamaa K (2004) Mitochondrial DNA polymorphisms as risk factors for Parkinson’s disease and Parkinson’s disease dementia. Hum Genet 115(1):29–35.  https://doi.org/10.1007/s00439-004-1123-9 PubMedCrossRefGoogle Scholar
  5. Bales KR (2004) Neurodegenerative disease research in the 21st century. Drug Discov Today 9(13):553–556.  https://doi.org/10.1016/S1359-6446(04)03120-4 PubMedCrossRefGoogle Scholar
  6. Baloyannis SJ (2006) Mitochondrial alterations in Alzheimer's disease. J Alzheimers Disease 9(2):119–126CrossRefGoogle Scholar
  7. Barroso N, Campos Y, Huertas R, Esteban J, Molina JA, Alonso A, Gutierrez-Rivas E, Arenas J (1993) Respiratory chain enzyme activities in lymphocytes from untreated patients with Parkinson disease. Clin Chem 39(4):667–669PubMedGoogle Scholar
  8. Bates GP (2005) History of genetic disease: the molecular genetics of Huntington disease - a history. Nat Rev Genet 6(10):766–773PubMedCrossRefGoogle Scholar
  9. Beal MF, Brouillet E, Jenkins BG, Ferrante RJ, Kowall NW, Miller JM, Storey E, Srivastava R, Rosen BR, Hyman BT (1993) Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J Neurosci 13(10):4181–4192PubMedGoogle Scholar
  10. Berardelli A, Wenning GK, Antonini A, Berg D, Bloem BR, Bonifati V, Brooks D, Burn DJ, Colosimo C, Fanciulli A, Ferreira J, Gasser T, Grandas F, Kanovsky P, Kostic V, Kulisevsky J, Oertel W, Poewe W, Reese JP, Relja M, Ruzicka E, Schrag A, Seppi K, Taba P, Vidailhet M (2013) EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease. Eur J Neurol 20(1):16–34.  https://doi.org/10.1111/ene.12022 PubMedCrossRefGoogle Scholar
  11. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3(12):1301–1306PubMedCrossRefGoogle Scholar
  12. Blandini F, Nappi G, Greenamyre JT (1998) Quantitative study of mitochondrial complex I in platelets of parkinsonian patients. Mov Disord 13(1):11–15PubMedCrossRefGoogle Scholar
  13. Bose A, Beal MF (2016) Mitochondrial dysfunction in Parkinson’s disease. J Neurochem 139(Suppl 1):216–231.  https://doi.org/10.1111/jnc.13731 PubMedCrossRefGoogle Scholar
  14. Bossy-Wetzel E, Petrilli A, Knott AB (2008) Mutant huntingtin and mitochondrial dysfunction. Trends Neurosci 31(12):609–616PubMedPubMedCentralCrossRefGoogle Scholar
  15. Braak H, Braak E (1995) Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiol Aging 16(3):271–278. discussion 278-284PubMedCrossRefGoogle Scholar
  16. Browne SE, Bowling AC, MacGarvey U, Baik MJ, Berger SC, Muqit MM, Bird ED, Beal MF (1997) Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann Neurol 41(5):646–653.  https://doi.org/10.1002/ana.410410514 PubMedCrossRefGoogle Scholar
  17. Bubber P, Haroutunian V, Fisch G, Blass JP, Gibson GE (2005) Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Ann Neurol 57(5):695–703.  https://doi.org/10.1002/ana.20474 PubMedCrossRefGoogle Scholar
  18. Calkins MJ, Reddy PH (2011) Amyloid beta impairs mitochondrial anterograde transport and degenerates synapses in Alzheimer’s disease neurons. Biochim Biophys Acta 1812(4):507–513.  https://doi.org/10.1016/j.bbadis.2011.01.007 PubMedPubMedCentralCrossRefGoogle Scholar
  19. Calkins MJ, Manczak M, Mao P, Shirendeb U, Reddy PH (2011) Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer’s disease. Hum Mol Genet 20(23):4515–4529.  https://doi.org/10.1093/hmg/ddr381 PubMedPubMedCentralCrossRefGoogle Scholar
  20. Carvalho C, Correia SC, Cardoso S, Placido AI, Candeias E, Duarte AI, Moreira PI (2015) The role of mitochondrial disturbances in Alzheimer, Parkinson and Huntington diseases. Expert Rev Neurother 15(8):867–884.  https://doi.org/10.1586/14737175.2015.1058160 PubMedCrossRefGoogle Scholar
  21. Caspersen C, Wang N, Yao J, Sosunov A, Chen X, Lustbader JW, Xu HW, Stern D, McKhann G, Yan SD (2005) Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer’s disease. FASEB J 19(14):2040–2041.  https://doi.org/10.1096/fj.05-3735fje PubMedCrossRefGoogle Scholar
  22. Celsi F, Pizzo P, Brini M, Leo S, Fotino C, Pinton P, Rizzuto R (2009) Mitochondria, calcium and cell death: a deadly triad in neurodegeneration. Biochim Biophys Acta 1787(5):335–344.  https://doi.org/10.1016/j.bbabio.2009.02.021 PubMedPubMedCentralCrossRefGoogle Scholar
  23. Chang DT, Rintoul GL, Pandipati S, Reynolds IJ (2006) Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol Dis 22(2):388–400.  https://doi.org/10.1016/j.nbd.2005.12.007 PubMedCrossRefGoogle Scholar
  24. Chinta SJ, Andersen JK (2008) Redox imbalance in Parkinson’s disease. Biochim Biophys Acta 1780(11):1362–1367PubMedPubMedCentralCrossRefGoogle Scholar
  25. Cho DH, Nakamura T, Fang J, Cieplak P, Godzik A, Gu Z, Lipton SA (2009) S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 324(5923):102–105.  https://doi.org/10.1126/science.1171091 PubMedPubMedCentralCrossRefGoogle Scholar
  26. Choo YS, Johnson GV, MacDonald M, Detloff PJ, Lesort M (2004) Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum Mol Genet 13(14):1407–1420.  https://doi.org/10.1093/hmg/ddh162 PubMedCrossRefGoogle Scholar
  27. Choong CJ, Mochizuki H (2017) Inappropriate trafficking of damaged mitochondria in Parkinson's disease. Stem Cell Investig 4:17.  https://doi.org/10.21037/sci.2017.02.07 PubMedPubMedCentralCrossRefGoogle Scholar
  28. Chou JL, Shenoy DV, Thomas N, Choudhary PK, Laferla FM, Goodman SR, Breen GA (2011) Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer’s disease. J Proteome 74(4):466–479.  https://doi.org/10.1016/j.jprot.2010.12.012 CrossRefGoogle Scholar
  29. Ciron C, Zheng L, Bobela W, Knott GW, Leone TC, Kelly DP, Schneider BL (2015) PGC-1alpha activity in nigral dopamine neurons determines vulnerability to alpha-synuclein. Acta Neuropathol Commun 3:16.  https://doi.org/10.1186/s40478-015-0200-8 PubMedPubMedCentralCrossRefGoogle Scholar
  30. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441(7097):1162–1166.  https://doi.org/10.1038/nature04779 PubMedCrossRefGoogle Scholar
  31. Correia SC, Santos RX, Cardoso S, Carvalho C, Candeias E, Duarte AI, Placido AI, Santos MS, Moreira PI (2012a) Alzheimer disease as a vascular disorder: where do mitochondria fit? Exp Gerontol 47(11):878–886.  https://doi.org/10.1016/j.exger.2012.07.006 PubMedCrossRefGoogle Scholar
  32. Correia SC, Santos RX, Perry G, Zhu X, Moreira PI, Smith MA (2012b) Mitochondrial importance in Alzheimer’s, Huntington’s and Parkinson’s diseases. Adv Exp Med Biol 724:205–221.  https://doi.org/10.1007/978-1-4614-0653-2_16 PubMedCrossRefGoogle Scholar
  33. Correia SC, Perry G, Moreira PI (2016) Mitochondrial traffic jams in Alzheimer’s disease - pinpointing the roadblocks. Biochim Biophys Acta 1862(10):1909–1917.  https://doi.org/10.1016/j.bbadis.2016.07.010 PubMedCrossRefGoogle Scholar
  34. Covarrubias-Pinto A, Moll P, Solis-Maldonado M, Acuna AI, Riveros A, Miro MP, Papic E, Beltran FA, Cepeda C, Concha II, Brauchi S, Castro MA (2015) Beyond the redox imbalance: oxidative stress contributes to an impaired GLUT3 modulation in Huntington’s disease. Free Radic Biol Med 89:1085–1096.  https://doi.org/10.1016/j.freeradbiomed.2015.09.024 PubMedPubMedCentralCrossRefGoogle Scholar
  35. Crouch PJ, Blake R, Duce JA, Ciccotosto GD, Li QX, Barnham KJ, Curtain CC, Cherny RA, Cappai R, Dyrks T, Masters CL, Trounce IA (2005) Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42. J Neurosci 25(3):672–679.  https://doi.org/10.1523/JNEUROSCI.4276-04.2005 PubMedCrossRefGoogle Scholar
  36. Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D (2006) Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127(1):59–69.  https://doi.org/10.1016/j.cell.2006.09.015 PubMedCrossRefGoogle Scholar
  37. Damiano M, Diguet E, Malgorn C, D'Aurelio M, Galvan L, Petit F, Benhaim L, Guillermier M, Houitte D, Dufour N, Hantraye P, Canals JM, Alberch J, Delzescaux T, Deglon N, Beal MF, Brouillet E (2013) A role of mitochondrial complex II defects in genetic models of Huntington’s disease expressing N-terminal fragments of mutant huntingtin. Hum Mol Genet 22(19):3869–3882.  https://doi.org/10.1093/hmg/ddt242 PubMedPubMedCentralCrossRefGoogle Scholar
  38. Deng H, Dodson MW, Huang H, Guo M (2008) The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A 105(38):14503–14508.  https://doi.org/10.1073/pnas.0803998105 PubMedPubMedCentralCrossRefGoogle Scholar
  39. Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK (2006) Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer’s disease brain is associated with mitochondrial dysfunction. J Neurosci 26(35):9057–9068.  https://doi.org/10.1523/JNEUROSCI.1469-06.2006 PubMedCrossRefGoogle Scholar
  40. Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS (2010) Early deficits in synaptic mitochondria in an Alzheimer’s disease mouse model. Proc Natl Acad Sci U S A 107(43):18670–18675.  https://doi.org/10.1073/pnas.1006586107 PubMedPubMedCentralCrossRefGoogle Scholar
  41. Dugger BN, Dickson DW (2017) Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 9(7).  https://doi.org/10.1101/cshperspect.a028035
  42. Durcan TM, Fon EA (2015) The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications. Genes Dev 29(10):989–999.  https://doi.org/10.1101/gad.262758.115 PubMedPubMedCentralCrossRefGoogle Scholar
  43. Ebneth A, Godemann R, Stamer K, Illenberger S, Trinczek B, Mandelkow E (1998) Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer’s disease. J Cell Biol 143(3):777–794PubMedPubMedCentralCrossRefGoogle Scholar
  44. Ekstrand MI, Terzioglu M, Galter D, Zhu S, Hofstetter C, Lindqvist E, Thams S, Bergstrand A, Hansson FS, Trifunovic A, Hoffer B, Cullheim S, Mohammed AH, Olson L, Larsson NG (2007) Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons. Proc Natl Acad Sci U S A 104(4):1325–1330PubMedPubMedCentralCrossRefGoogle Scholar
  45. Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, Radi E (2012) Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 322(1–2):254–262.  https://doi.org/10.1016/j.jns.2012.05.030 PubMedCrossRefGoogle Scholar
  46. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408(6809):239–247.  https://doi.org/10.1038/35041687 PubMedCrossRefGoogle Scholar
  47. Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55(3):259–272PubMedCrossRefGoogle Scholar
  48. Franco-Iborra S, Vila M, Perier C (2016) The Parkinson disease mitochondrial hypothesis: where are we at? Neuroscientist 22(3):266–277.  https://doi.org/10.1177/1073858415574600 PubMedCrossRefGoogle Scholar
  49. Friedland RP, Jagust WJ, Huesman RH, Koss E, Knittel B, Mathis CA, Ober BA, Mazoyer BM, Budinger TF (1989) Regional cerebral glucose transport and utilization in Alzheimer’s disease. Neurology 39(11):1427–1434PubMedCrossRefGoogle Scholar
  50. Gan X, Huang S, Wu L, Wang Y, Hu G, Li G, Zhang H, Yu H, Swerdlow RH, Chen JX, Yan SS (2014) Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer’s disease cybrid cell. Biochim Biophys Acta 1842(2):220–231.  https://doi.org/10.1016/j.bbadis.2013.11.009 PubMedCrossRefGoogle Scholar
  51. Gao J, Wang L, Liu J, Xie F, Su B, Wang X (2017) Abnormalities of mitochondrial dynamics in neurodegenerative diseases. Antioxidants (Basel) 6(2).  https://doi.org/10.3390/antiox6020025
  52. Gash DM, Rutland K, Hudson NL, Sullivan PG, Bing G, Cass WA, Pandya JD, Liu M, Choi DY, Hunter RL, Gerhardt GA, Smith CD, Slevin JT, Prince TS (2008) Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity. Ann Neurol 63(2):184–192PubMedCrossRefGoogle Scholar
  53. Gauthier LR, Charrin BC, Borrell-Pages M, Dompierre JP, Rangone H, Cordelieres FP, De Mey J, MacDonald ME, Lessmann V, Humbert S, Saudou F (2004) Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 118(1):127–138.  https://doi.org/10.1016/j.cell.2004.06.018 PubMedCrossRefGoogle Scholar
  54. Geisler S, Holmstrom KM, Treis A, Skujat D, Weber SS, Fiesel FC, Kahle PJ, Springer W (2010) The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations. Autophagy 6(7):871–878PubMedCrossRefGoogle Scholar
  55. Gil JM, Rego AC (2008) Mechanisms of neurodegeneration in Huntington’s disease. Eur J Neurosci 27(11):2803–2820.  https://doi.org/10.1111/j.1460-9568.2008.06310.x PubMedCrossRefGoogle Scholar
  56. Goldman JG, Postuma R (2014) Premotor and nonmotor features of Parkinson’s disease. Curr Opin Neurol 27(4):434–441.  https://doi.org/10.1097/WCO.0000000000000112 PubMedPubMedCentralCrossRefGoogle Scholar
  57. Grimm A, Eckert A (2017) Brain aging and neurodegeneration: from a mitochondrial point of view. J Neurochem 143(4):418–431.  https://doi.org/10.1111/jnc.14037 PubMedPubMedCentralCrossRefGoogle Scholar
  58. Gu M, Gash MT, Mann VM, Javoy-Agid F, Cooper JM, Schapira AH (1996) Mitochondrial defect in Huntington’s disease caudate nucleus. Ann Neurol 39(3):385–389.  https://doi.org/10.1002/ana.410390317 PubMedCrossRefGoogle Scholar
  59. Guardia-Laguarta C, Area-Gomez E, Rub C, Liu Y, Magrane J, Becker D, Voos W, Schon EA, Przedborski S (2014) alpha-Synuclein is localized to mitochondria-associated ER membranes. J Neurosci 34(1):249–259.  https://doi.org/10.1523/JNEUROSCI.2507-13.2014 PubMedPubMedCentralCrossRefGoogle Scholar
  60. Guedes-Dias P, de Proenca J, Soares TR, Leitao-Rocha A, Pinho BR, Duchen MR, Oliveira JM (2015) HDAC6 inhibition induces mitochondrial fusion, autophagic flux and reduces diffuse mutant huntingtin in striatal neurons. Biochim Biophys Acta 1852(11):2484–2493.  https://doi.org/10.1016/j.bbadis.2015.08.012 PubMedCrossRefGoogle Scholar
  61. Guedes-Dias P, Pinho BR, Soares TR, de Proenca J, Duchen MR, Oliveira JM (2016) Mitochondrial dynamics and quality control in Huntington’s disease. Neurobiol Dis 90:51–57.  https://doi.org/10.1016/j.nbd.2015.09.008 PubMedCrossRefGoogle Scholar
  62. Guidetti P, Charles V, Chen EY, Reddy PH, Kordower JH, Whetsell WO Jr, Schwarcz R, Tagle DA (2001) Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production. Exp Neurol 169(2):340–350.  https://doi.org/10.1006/exnr.2000.7626 PubMedCrossRefGoogle Scholar
  63. Haas RH, Nasirian F, Nakano K, Ward D, Pay M, Hill R, Shults CW (1995) Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson’s disease. Ann Neurol 37(6):714–722PubMedCrossRefGoogle Scholar
  64. Haun F, Nakamura T, Shiu AD, Cho DH, Tsunemi T, Holland EA, La Spada AR, Lipton SA (2013) S-nitrosylation of dynamin-related protein 1 mediates mutant huntingtin-induced mitochondrial fragmentation and neuronal injury in Huntington’s disease. Antioxid Redox Signal 19(11):1173–1184.  https://doi.org/10.1089/ars.2012.4928 PubMedPubMedCentralCrossRefGoogle Scholar
  65. Hansson Petersen CA, Alikhani N, Behbahani H, Wiehager B, Pavlov PF, Alafuzoff I, Leinonen V, Ito A, Winblad B, Glaser E, Ankarcrona M (2008) The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A 105(35):13145–13150.  https://doi.org/10.1073/pnas.0806192105 PubMedPubMedCentralCrossRefGoogle Scholar
  66. Haylett W, Swart C, van der Westhuizen F, van Dyk H, van der Merwe L, van der Merwe C, Loos B, Carr J, Kinnear C, Bardien S (2016) Altered mitochondrial respiration and other features of mitochondrial function in parkin-mutant fibroblasts from Parkinson’disease patients. Parkinsons Dis 2016:1819209.  https://doi.org/10.1155/2016/1819209 PubMedPubMedCentralGoogle Scholar
  67. Hering T, Birth N, Taanman JW, Orth M (2015) Selective striatal mtDNA depletion in end-stage Huntington's disease R6/2 mice. Exp Neurol 266:22–29.  https://doi.org/10.1016/j.expneurol.2015.02.004 PubMedCrossRefGoogle Scholar
  68. Herrup K (2015) The case for rejecting the amyloid cascade hypothesis. Nat Neurosci 18(6):794–799.  https://doi.org/10.1038/nn.4017 PubMedCrossRefGoogle Scholar
  69. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21(9):3017–3023PubMedGoogle Scholar
  70. Hollenbeck PJ, Saxton WM (2005) The axonal transport of mitochondria. J Cell Sci 118(Pt 23):5411–5419.  https://doi.org/10.1242/jcs.02745 PubMedPubMedCentralCrossRefGoogle Scholar
  71. Hsieh CH, Shaltouki A, Gonzalez AE, Bettencourt da Cruz A, Burbulla LF, St Lawrence E, Schule B, Krainc D, Palmer TD, Wang X (2016) Functional impairment in miro degradation and mitophagy is a shared feature in familial and sporadic Parkinson’s disease. Cell Stem Cell 19(6):709–724.  https://doi.org/10.1016/j.stem.2016.08.002 PubMedPubMedCentralCrossRefGoogle Scholar
  72. Hsu LJ, Sagara Y, Arroyo A, Rockenstein E, Sisk A, Mallory M, Wong J, Takenouchi T, Hashimoto M, Masliah E (2000) Alpha-synuclein promotes mitochondrial deficit and oxidative stress. Am J Pathol 157(2):401–410PubMedPubMedCentralCrossRefGoogle Scholar
  73. Jagust WJ, Seab JP, Huesman RH, Valk PE, Mathis CA, Reed BR, Coxson PG, Budinger TF (1991) Diminished glucose transport in Alzheimer's disease: dynamic PET studies. J Cereb Blood Flow Metab 11(2):323–330.  https://doi.org/10.1038/jcbfm.1991.65 PubMedCrossRefGoogle Scholar
  74. Jellinger KA (2009) Recent advances in our understanding of neurodegeneration. J Neural Transm 116(9):1111–1162.  https://doi.org/10.1007/s00702-009-0240-y PubMedCrossRefGoogle Scholar
  75. Jellinger KA (2010) Basic mechanisms of neurodegeneration: a critical update. J Cell Mol Med 14(3):457–487.  https://doi.org/10.1111/j.1582-4934.2010.01010.x PubMedPubMedCentralGoogle Scholar
  76. Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, Banerjee S, Youle RJ (2014) PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol 205(2):143–153.  https://doi.org/10.1083/jcb.201402104 PubMedPubMedCentralCrossRefGoogle Scholar
  77. Kann O, Kovacs R (2007) Mitochondria and neuronal activity. Am J Physiol Cell Physiol 292(2):C641–C657.  https://doi.org/10.1152/ajpcell.00222.2006 PubMedCrossRefGoogle Scholar
  78. Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10(9):698–712.  https://doi.org/10.1038/nrd3505 PubMedCrossRefGoogle Scholar
  79. Khalil B, El Fissi N, Aouane A, Cabirol-Pol MJ, Rival T, Lievens JC (2015) PINK1-induced mitophagy promotes neuroprotection in Huntington’s disease. Cell Death Dis 6:e1617.  https://doi.org/10.1038/cddis.2014.581 PubMedPubMedCentralCrossRefGoogle Scholar
  80. Kieburtz K (2016) Treating neurodegenerative disease before illness: a challenge for the 21st century. Lancet Neurol 15(6):540–541.  https://doi.org/10.1016/S1474-4422(16)30001-1 PubMedCrossRefGoogle Scholar
  81. Kim J, Moody JP, Edgerly CK, Bordiuk OL, Cormier K, Smith K, Beal MF, Ferrante RJ (2010) Mitochondrial loss, dysfunction and altered dynamics in Huntington’s disease. Hum Mol Genet 19(20):3919–3935.  https://doi.org/10.1093/hmg/ddq306 PubMedPubMedCentralCrossRefGoogle Scholar
  82. Kim GH, Kim JE, Rhie SJ, Yoon S (2015) The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol 24(4):325–340.  https://doi.org/10.5607/en.2015.24.4.325 PubMedPubMedCentralCrossRefGoogle Scholar
  83. Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF (1997) Energy metabolism defects in Huntington’s disease and effects of coenzyme Q10. Ann Neurol 41(2):160–165.  https://doi.org/10.1002/ana.410410206 PubMedCrossRefGoogle Scholar
  84. Kovari E, Horvath J, Bouras C (2009) Neuropathology of Lewy body disorders. Brain Res Bull 80(4–5):203–210.  https://doi.org/10.1016/j.brainresbull.2009.06.018 PubMedCrossRefGoogle Scholar
  85. Krige D, Carroll MT, Cooper JM, Marsden CD, Schapira AH (1992) Platelet mitochondrial function in Parkinson’s disease. The Royal Kings and Queens Parkinson Disease Research Group. Ann Neurol 32(6):782–788PubMedCrossRefGoogle Scholar
  86. Kuhl DE, Phelps ME, Markham CH, Metter EJ, Riege WH, Winter J (1982) Cerebral metabolism and atrophy in Huntington’s disease determined by 18FDG and computed tomographic scan. Ann Neurol 12(5):425–434.  https://doi.org/10.1002/ana.410120504 PubMedCrossRefGoogle Scholar
  87. Kuwert T, Lange HW, Langen KJ, Herzog H, Aulich A, Feinendegen LE (1989) Cerebral glucose consumption measured by PET in patients with and without psychiatric symptoms of Huntington’s disease. Psychiatry Res 29(3):361–362PubMedCrossRefGoogle Scholar
  88. Kwon SK, Hirabayashi Y, Polleux F (2016) Organelle-specific sensors for monitoring Ca2+ dynamics in neurons. Front Synaptic Neurosci 8:29.  https://doi.org/10.3389/fnsyn.2016.00029 PubMedPubMedCentralCrossRefGoogle Scholar
  89. Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219(4587):979–980PubMedCrossRefGoogle Scholar
  90. Li XJ, Li SH, Sharp AH, Nucifora FC Jr, Schilling G, Lanahan A, Worley P, Snyder SH, Ross CA (1995) A huntingtin-associated protein enriched in brain with implications for pathology. Nature 378(6555):398–402.  https://doi.org/10.1038/378398a0 PubMedCrossRefGoogle Scholar
  91. Liang CL, Wang TT, Luby-Phelps K, German DC (2007) Mitochondria mass is low in mouse substantia nigra dopamine neurons: implications for Parkinson’s disease. Exp Neurol 203(2):370–380.  https://doi.org/10.1016/j.expneurol.2006.08.015 PubMedCrossRefGoogle Scholar
  92. Lin MY, Sheng ZH (2015) Regulation of mitochondrial transport in neurons. Exp Cell Res 334(1):35–44.  https://doi.org/10.1016/j.yexcr.2015.01.004 PubMedPubMedCentralCrossRefGoogle Scholar
  93. Liot G, Bossy B, Lubitz S, Kushnareva Y, Sejbuk N, Bossy-Wetzel E (2009) Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death Differ 16(6):899–909PubMedPubMedCentralCrossRefGoogle Scholar
  94. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of A beta accumulation in Alzheimer’s disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15(9):1437–1449.  https://doi.org/10.1093/hmg/ddl066 PubMedCrossRefGoogle Scholar
  95. Martin-Maestro P, Gargini R, Perry G, Avila J, Garcia-Escudero V (2016) PARK2 enhancement is able to compensate mitophagy alterations found in sporadic Alzheimer’s disease. Hum Mol Genet 25(4):792–806.  https://doi.org/10.1093/hmg/ddv616 PubMedCrossRefGoogle Scholar
  96. Martin-Maestro P, Gargini R, AS A, Garcia E, Anton LC, Noggle S, Arancio O, Avila J, Garcia-Escudero V (2017) Mitophagy failure in fibroblasts and iPSC-derived neurons of Alzheimer’s disease-associated presenilin 1 mutation. Front Mol Neurosci 10:291.  https://doi.org/10.3389/fnmol.2017.00291 PubMedPubMedCentralCrossRefGoogle Scholar
  97. Mastrogiacomo F, Bergeron C, Kish SJ (1993) Brain alpha-ketoglutarate dehydrogenase complex activity in Alzheimer’s disease. J Neurochem 61(6):2007–2014PubMedCrossRefGoogle Scholar
  98. McWilliams TG, Muqit MM (2017) PINK1 and Parkin: emerging themes in mitochondrial homeostasis. Curr Opin Cell Biol 45:83–91.  https://doi.org/10.1016/j.ceb.2017.03.013 PubMedCrossRefGoogle Scholar
  99. Moreira PI, Siedlak SL, Wang X, Santos MS, Oliveira CR, Tabaton M, Nunomura A, Szweda LI, Aliev G, Smith MA, Zhu X, Perry G (2007a) Autophagocytosis of mitochondria is prominent in Alzheimer disease. J Neuropathol Exp Neurol 66(6):525–532.  https://doi.org/10.1097/01.jnen.0000240476.73532.b0 PubMedCrossRefGoogle Scholar
  100. Moreira PI, Siedlak SL, Wang X, Santos MS, Oliveira CR, Tabaton M, Nunomura A, Szweda LI, Aliev G, Smith MA, Zhu X, Perry G (2007b) Increased autophagic degradation of mitochondria in Alzheimer disease. Autophagy 3(6):614–615PubMedCrossRefGoogle Scholar
  101. Moreira PI, Zhu X, Wang X, Lee HG, Nunomura A, Petersen RB, Perry G, Smith MA (2010) Mitochondria: a therapeutic target in neurodegeneration. Biochim Biophys Acta 1802(1):212–220.  https://doi.org/10.1016/j.bbadis.2009.10.007 PubMedCrossRefGoogle Scholar
  102. Mortiboys H, Johansen KK, Aasly JO, Bandmann O (2010) Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2. Neurology 75(22):2017–2020.  https://doi.org/10.1212/WNL.0b013e3181ff9685 PubMedCrossRefGoogle Scholar
  103. Muangpaisan W, Mathews A, Hori H, Seidel D (2011) A systematic review of the worldwide prevalence and incidence of Parkinson’s disease. J Med Assoc Thai 94(6):749–755PubMedGoogle Scholar
  104. Mutisya EM, Bowling AC, Beal MF (1994) Cortical cytochrome oxidase activity is reduced in Alzheimer’s disease. J Neurochem 63(6):2179–2184PubMedCrossRefGoogle Scholar
  105. Naia L, Ferreira IL, Ferreiro E, Rego AC (2017) Mitochondrial Ca2+ handling in Huntington’s and Alzheimer’s diseases - role of ER-mitochondria crosstalk. Biochem Biophys Res Commun 483(4):1069–1077.  https://doi.org/10.1016/j.bbrc.2016.07.122 PubMedCrossRefGoogle Scholar
  106. Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183(5):795–803.  https://doi.org/10.1083/jcb.200809125 PubMedPubMedCentralCrossRefGoogle Scholar
  107. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA (2001) Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60(8):759–767PubMedCrossRefGoogle Scholar
  108. Oliveira JM (2010) Nature and cause of mitochondrial dysfunction in Huntington's disease: focusing on huntingtin and the striatum. J Neurochem 114(1):1–12.  https://doi.org/10.1111/j.1471-4159.2010.06741.x PubMedGoogle Scholar
  109. Orr AL, Li S, Wang CE, Li H, Wang J, Rong J, Xu X, Mastroberardino PG, Greenamyre JT, Li XJ (2008) N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking. J Neurosci 28(11):2783–2792.  https://doi.org/10.1523/JNEUROSCI.0106-08.2008 PubMedPubMedCentralCrossRefGoogle Scholar
  110. Panov AV, Gutekunst CA, Leavitt BR, Hayden MR, Burke JR, Strittmatter WJ, Greenamyre JT (2002) Early mitochondrial calcium defects in Huntington’s disease are a direct effect of polyglutamines. Nat Neurosci 5(8):731–736.  https://doi.org/10.1038/nn884 PubMedCrossRefGoogle Scholar
  111. Papkovskaia TD, Chau KY, Inesta-Vaquera F, Papkovsky DB, Healy DG, Nishio K, Staddon J, Duchen MR, Hardy J, Schapira AH, Cooper JM (2012) G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization. Hum Mol Genet 21(19):4201–4213.  https://doi.org/10.1093/hmg/dds244 PubMedPubMedCentralCrossRefGoogle Scholar
  112. Parker WD Jr, Boyson SJ, Parks JK (1989) Abnormalities of the electron transport chain in idiopathic Parkinson’s disease. Ann Neurol 26(6):719–723PubMedCrossRefGoogle Scholar
  113. Parker WD Jr, Parks JK, Swerdlow RH (2008) Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res 1189:215–218PubMedCrossRefGoogle Scholar
  114. Penn AM, Roberts T, Hodder J, Allen PS, Zhu G, Martin WR (1995) Generalized mitochondrial dysfunction in Parkinson’s disease detected by magnetic resonance spectroscopy of muscle. Neurology 45(11):2097–2099PubMedCrossRefGoogle Scholar
  115. Persson T, Popescu BO, Cedazo-Minguez A (2014) Oxidative stress in Alzheimer’s disease: why did antioxidant therapy fail? Oxidative Med Cell Longev 2014:427318.  https://doi.org/10.1155/2014/427318 CrossRefGoogle Scholar
  116. Polyzos AA, McMurray CT (2017) The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington’s disease. Mech Ageing Dev 161(Pt A):181–197.  https://doi.org/10.1016/j.mad.2016.09.003 PubMedCrossRefGoogle Scholar
  117. Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ (2008) The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 105(5):1638–1643.  https://doi.org/10.1073/pnas.0709336105 PubMedPubMedCentralCrossRefGoogle Scholar
  118. Pozo Devoto VM, Dimopoulos N, Alloatti M, Pardi MB, Saez TM, Otero MG, Cromberg LE, Marin-Burgin A, Scassa ME, Stokin GB, Schinder AF, Sevlever G, Falzone TL (2017) alphaSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson’s disease. Sci Rep 7(1):5042.  https://doi.org/10.1038/s41598-017-05334-9 PubMedPubMedCentralCrossRefGoogle Scholar
  119. Qin W, Haroutunian V, Katsel P, Cardozo CP, Ho L, Buxbaum JD, Pasinetti GM (2009) PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Arch Neurol 66(3):352–361.  https://doi.org/10.1001/archneurol.2008.588 PubMedPubMedCentralCrossRefGoogle Scholar
  120. Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362(4):329–344.  https://doi.org/10.1056/NEJMra0909142 PubMedCrossRefGoogle Scholar
  121. Quintanilla RA, Dolan PJ, Jin YN, Johnson GV (2012) Truncated tau and Abeta cooperatively impair mitochondria in primary neurons. Neurobiol Aging 33(3):619.e625–619.e635.  https://doi.org/10.1016/j.neurobiolaging.2011.02.007 CrossRefGoogle Scholar
  122. Reddy PH, Reddy TP (2011) Mitochondria as a therapeutic target for aging and neurodegenerative diseases. Curr Alzheimer Res 8(4):393–409PubMedPubMedCentralCrossRefGoogle Scholar
  123. Reiner A, Albin RL, Anderson KD, D'Amato CJ, Penney JB, Young AB (1988) Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci U S A 85(15):5733–5737PubMedPubMedCentralCrossRefGoogle Scholar
  124. Resende R, Moreira PI, Proenca T, Deshpande A, Busciglio J, Pereira C, Oliveira CR (2008) Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Free Radic Biol Med 44(12):2051–2057.  https://doi.org/10.1016/j.freeradbiomed.2008.03.012 PubMedCrossRefGoogle Scholar
  125. Rhein V, Song X, Wiesner A, Ittner LM, Baysang G, Meier F, Ozmen L, Bluethmann H, Drose S, Brandt U, Savaskan E, Czech C, Gotz J, Eckert A (2009) Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice. Proc Natl Acad Sci U S A 106(47):20057–20062.  https://doi.org/10.1073/pnas.0905529106 PubMedPubMedCentralCrossRefGoogle Scholar
  126. Rodolfo C, Campello S, Cecconi F (2017) Mitophagy in neurodegenerative diseases. Neurochem Int.  https://doi.org/10.1016/j.neuint.2017.08.004
  127. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54(3):823–827PubMedCrossRefGoogle Scholar
  128. Schapira AHV, Chaudhuri KR, Jenner P (2017) Non-motor features of Parkinson disease. Nat Rev Neurosci 18(7):435–450.  https://doi.org/10.1038/nrn.2017.62 PubMedCrossRefGoogle Scholar
  129. Seo AY, Joseph AM, Dutta D, Hwang JC, Aris JP, Leeuwenburgh C (2010) New insights into the role of mitochondria in aging: mitochondrial dynamics and more. J Cell Sci 123(Pt 15):2533–2542.  https://doi.org/10.1242/jcs.070490 PubMedPubMedCentralCrossRefGoogle Scholar
  130. Shaerzadeh F, Motamedi F, Minai-Tehrani D, Khodagholi F (2014) Monitoring of neuronal loss in the hippocampus of Abeta-injected rat: autophagy, mitophagy, and mitochondrial biogenesis stand against apoptosis. NeuroMolecular Med 16(1):175–190.  https://doi.org/10.1007/s12017-013-8272-8 PubMedCrossRefGoogle Scholar
  131. Shah K, Desilva S, Abbruscato T (2012) The role of glucose transporters in brain disease: diabetes and Alzheimer’s disease. Int J Mol Sci 13(10):12629–12655.  https://doi.org/10.3390/ijms131012629 PubMedPubMedCentralCrossRefGoogle Scholar
  132. Sheng ZH (2014) Mitochondrial trafficking and anchoring in neurons: new insight and implications. J Cell Biol 204(7):1087–1098.  https://doi.org/10.1083/jcb.201312123 PubMedPubMedCentralCrossRefGoogle Scholar
  133. Sheng ZH, Cai Q (2012) Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration. Nat Rev Neurosci 13(2):77–93.  https://doi.org/10.1038/nrn3156 PubMedPubMedCentralCrossRefGoogle Scholar
  134. Sheng B, Wang X, Su B, Lee HG, Casadesus G, Perry G, Zhu X (2012) Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease. J Neurochem 120(3):419–429.  https://doi.org/10.1111/j.1471-4159.2011.07581.x PubMedCrossRefGoogle Scholar
  135. Sherer TB, Betarbet R, Stout AK, Lund S, Baptista M, Panov AV, Cookson MR, Greenamyre JT (2002) An in vitro model of Parkinson’s disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci 22(16):7006–7015. doi:20026721PubMedGoogle Scholar
  136. Sherer TB, Richardson JR, Testa CM, Seo BB, Panov AV, Yagi T, Matsuno-Yagi A, Miller GW, Greenamyre JT (2007) Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson’s disease. J Neurochem 100(6):1469–1479PubMedGoogle Scholar
  137. Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, Troconso JC, Dawson VL, Dawson TM (2011) PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson’s disease. Cell 144(5):689–702.  https://doi.org/10.1016/j.cell.2011.02.010 PubMedPubMedCentralCrossRefGoogle Scholar
  138. Shirendeb UP, Calkins MJ, Manczak M, Anekonda V, Dufour B, McBride JL, Mao P, Reddy PH (2012) Mutant huntingtin’s interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington’s disease. Hum Mol Genet 21(2):406–420.  https://doi.org/10.1093/hmg/ddr475 PubMedCrossRefGoogle Scholar
  139. Skovronsky DM, Lee VM, Trojanowski JQ (2006) Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol 1:151–170.  https://doi.org/10.1146/annurev.pathol.1.110304.100113 PubMedCrossRefGoogle Scholar
  140. Song W, Chen J, Petrilli A, Liot G, Klinglmayr E, Zhou Y, Poquiz P, Tjong J, Pouladi MA, Hayden MR, Masliah E, Ellisman M, Rouiller I, Schwarzenbacher R, Bossy B, Perkins G, Bossy-Wetzel E (2011) Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity. Nat Med 17(3):377–382.  https://doi.org/10.1038/nm.2313 PubMedPubMedCentralCrossRefGoogle Scholar
  141. Spillantini MG, Goedert M (2000) The alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Ann N Y Acad Sci 920:16–27PubMedCrossRefGoogle Scholar
  142. Squitieri F, Cannella M, Sgarbi G, Maglione V, Falleni A, Lenzi P, Baracca A, Cislaghi G, Saft C, Ragona G, Russo MA, Thompson LM, Solaini G, Fornai F (2006) Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for Huntington disease mutation. Mech Ageing Dev 127(2):217–220PubMedCrossRefGoogle Scholar
  143. Stevens DA, Lee Y, Kang HC, Lee BD, Lee YI, Bower A, Jiang H, Kang SU, Andrabi SA, Dawson VL, Shin JH, Dawson TM (2015) Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration. Proc Natl Acad Sci U S A 112(37):11696–11701.  https://doi.org/10.1073/pnas.1500624112 PubMedPubMedCentralCrossRefGoogle Scholar
  144. Su YC, Qi X (2013) Inhibition of excessive mitochondrial fission reduced aberrant autophagy and neuronal damage caused by LRRK2 G2019S mutation. Hum Mol Genet 22(22):4545–4561.  https://doi.org/10.1093/hmg/ddt301 PubMedCrossRefGoogle Scholar
  145. Subramaniam SR, Chesselet MF (2013) Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog Neurobiol 106–107:17–32.  https://doi.org/10.1016/j.pneurobio.2013.04.004 PubMedCrossRefGoogle Scholar
  146. Sultana R, Butterfield DA (2013) Oxidative modification of brain proteins in Alzheimer’s disease: perspective on future studies based on results of redox proteomics studies. J Alzheimers Dis 33(Suppl 1):S243–S251.  https://doi.org/10.3233/JAD-2012-129018 PubMedGoogle Scholar
  147. Swerdlow RH, Khan SM (2004) A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease. Med Hypotheses 63(1):8–20.  https://doi.org/10.1016/j.mehy.2003.12.045 PubMedCrossRefGoogle Scholar
  148. Swerdlow RH, Parks JK, Miller SW, Tuttle JB, Trimmer PA, Sheehan JP, Bennett JP Jr, Davis RE, Parker WD Jr (1996) Origin and functional consequences of the complex I defect in Parkinson’s disease. Ann Neurol 40(4):663–671.  https://doi.org/10.1002/ana.410400417 PubMedCrossRefGoogle Scholar
  149. Swerdlow RH, Parks JK, Davis JN 2nd, Cassarino DS, Trimmer PA, Currie LJ, Dougherty J, Bridges WS, Bennett JP Jr, Wooten GF, Parker WD (1998) Matrilineal inheritance of complex I dysfunction in a multigenerational Parkinson’s disease family. Ann Neurol 44(6):873–881PubMedCrossRefGoogle Scholar
  150. Swerdlow RH, Burns JM, Khan SM (2014) The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives. Biochim Biophys Acta 1842(8):1219–1231.  https://doi.org/10.1016/j.bbadis.2013.09.010 PubMedCrossRefGoogle Scholar
  151. Taylor DJ, Krige D, Barnes PR, Kemp GJ, Carroll MT, Mann VM, Cooper JM, Marsden CD, Schapira AH (1994) A 31P magnetic resonance spectroscopy study of mitochondrial function in skeletal muscle of patients with Parkinson’s disease. J Neurol Sci 125(1):77–81PubMedCrossRefGoogle Scholar
  152. 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):8972–8979PubMedGoogle Scholar
  153. Trimmer PA, Borland MK (2005) Differentiated Alzheimer’s disease transmitochondrial cybrid cell lines exhibit reduced organelle movement. Antioxid Redox Signal 7(9–10):1101–1109.  https://doi.org/10.1089/ars.2005.7.1101 PubMedCrossRefGoogle Scholar
  154. Trushina E, Dyer RB, Badger JD 2nd, Ure D, Eide L, Tran DD, Vrieze BT, Legendre-Guillemin V, McPherson PS, Mandavilli BS, Van Houten B, Zeitlin S, McNiven M, Aebersold R, Hayden M, Parisi JE, Seeberg E, Dragatsis I, Doyle K, Bender A, Chacko C, McMurray CT (2004) Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol Cell Biol 24(18):8195–8209.  https://doi.org/10.1128/MCB.24.18.8195-8209.2004 PubMedPubMedCentralCrossRefGoogle Scholar
  155. Utton MA, Noble WJ, Hill JE, Anderton BH, Hanger DP (2005) Molecular motors implicated in the axonal transport of tau and alpha-synuclein. J Cell Sci 118(Pt 20):4645–4654.  https://doi.org/10.1242/jcs.02558 PubMedCrossRefGoogle Scholar
  156. Veech GA, Dennis J, Keeney PM, Fall CP, Swerdlow RH, Parker WD Jr, Bennett JP Jr (2000) Disrupted mitochondrial electron transport function increases expression of anti-apoptotic bcl-2 and bcl-X(L) proteins in SH-SY5Y neuroblastoma and in Parkinson disease cybrid cells through oxidative stress. J Neurosci Res 61(6):693–700PubMedCrossRefGoogle Scholar
  157. Vos M, Lauwers E, Verstreken P (2010) Synaptic mitochondria in synaptic transmission and organization of vesicle pools in health and disease. Front Synaptic Neurosci 2:139.  https://doi.org/10.3389/fnsyn.2010.00139 PubMedPubMedCentralCrossRefGoogle Scholar
  158. Vossel KA, Zhang K, Brodbeck J, Daub AC, Sharma P, Finkbeiner S, Cui B, Mucke L (2010) Tau reduction prevents Abeta-induced defects in axonal transport. Science 330(6001):198.  https://doi.org/10.1126/science.1194653 PubMedPubMedCentralCrossRefGoogle Scholar
  159. Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J Neurosci 29(28):9090–9103.  https://doi.org/10.1523/JNEUROSCI.1357-09.2009 PubMedPubMedCentralCrossRefGoogle Scholar
  160. Wang X, Perry G, Smith MA, Zhu X (2010) Amyloid-beta-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons. Neurodegener Dis 7(1–3):56–59.  https://doi.org/10.1159/000283484 PubMedPubMedCentralCrossRefGoogle Scholar
  161. Wang X, Su B, Liu W, He X, Gao Y, Castellani RJ, Perry G, Smith MA, Zhu X (2011a) DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinium toxicity in neurons: implications for Parkinson’s disease. Aging Cell 10(5):807–823.  https://doi.org/10.1111/j.1474-9726.2011.00721.x PubMedPubMedCentralCrossRefGoogle Scholar
  162. Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, LaVoie MJ, Schwarz TL (2011b) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147(4):893–906.  https://doi.org/10.1016/j.cell.2011.10.018 PubMedPubMedCentralCrossRefGoogle Scholar
  163. Wang X, Petrie TG, Liu Y, Liu J, Fujioka H, Zhu X (2012a) Parkinson’s disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction. J Neurochem 121(5):830–839.  https://doi.org/10.1111/j.1471-4159.2012.07734.x PubMedPubMedCentralCrossRefGoogle Scholar
  164. Wang X, Yan MH, Fujioka H, Liu J, Wilson-Delfosse A, Chen SG, Perry G, Casadesus G, Zhu X (2012b) LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum Mol Genet 21(9):1931–1944.  https://doi.org/10.1093/hmg/dds003 PubMedPubMedCentralCrossRefGoogle Scholar
  165. Wang W, Wang X, Fujioka H, Hoppel C, Whone AL, Caldwell MA, Cullen PJ, Liu J, Zhu X (2016) Parkinson’s disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes. Nat Med 22(1):54–63.  https://doi.org/10.1038/nm.3983 PubMedCrossRefGoogle Scholar
  166. Westermann B (2010) Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 11(12):872–884.  https://doi.org/10.1038/nrm3013 PubMedCrossRefGoogle Scholar
  167. Weydt P, Pineda VV, Torrence AE, Libby RT, Satterfield TF, Lazarowski ER, Gilbert ML, Morton GJ, Bammler TK, Strand AD, Cui L, Beyer RP, Easley CN, Smith AC, Krainc D, Luquet S, Sweet IR, Schwartz MW, La Spada AR (2006) Thermoregulatory and metabolic defects in Huntington’s disease transgenic mice implicate PGC-1alpha in Huntington’s disease neurodegeneration. Cell Metab 4(5):349–362.  https://doi.org/10.1016/j.cmet.2006.10.004 PubMedCrossRefGoogle Scholar
  168. Wild P, Dikic I (2010) Mitochondria get a Parkin’ ticket. Nat Cell Biol 12(2):104–106.  https://doi.org/10.1038/ncb0210-104 PubMedCrossRefGoogle Scholar
  169. Wong YC, Holzbaur EL (2014) The regulation of autophagosome dynamics by huntingtin and HAP1 is disrupted by expression of mutant huntingtin, leading to defective cargo degradation. J Neurosci 34(4):1293–1305.  https://doi.org/10.1523/JNEUROSCI.1870-13.2014 PubMedPubMedCentralCrossRefGoogle Scholar
  170. Xie W, Chung KK (2012) Alpha-synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson’s disease. J Neurochem 122(2):404–414.  https://doi.org/10.1111/j.1471-4159.2012.07769.x PubMedCrossRefGoogle Scholar
  171. Yamano K, Matsuda N, Tanaka K (2016) The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation. EMBO Rep 17(3):300–316.  https://doi.org/10.15252/embr.201541486 PubMedPubMedCentralCrossRefGoogle Scholar
  172. Yao Z, Wood NW (2009) Cell death pathways in Parkinson’s disease: role of mitochondria. Antioxid Redox Signal 11(9):2135–2149.  https://doi.org/10.1089/ARS.2009.2624 PubMedCrossRefGoogle Scholar
  173. Yao J, Irwin RW, Zhao L, Nilsen J, Hamilton RT, Brinton RD (2009) Mitochondrial bioenergetic deficit precedes Alzheimer’s pathology in female mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 106(34):14670–14675.  https://doi.org/10.1073/pnas.0903563106 PubMedPubMedCentralCrossRefGoogle Scholar
  174. Ye X, Sun X, Starovoytov V, Cai Q (2015) Parkin-mediated mitophagy in mutant hAPP neurons and Alzheimer’s disease patient brains. Hum Mol Genet 24(10):2938–2951.  https://doi.org/10.1093/hmg/ddv056 PubMedPubMedCentralCrossRefGoogle Scholar
  175. Yoshino H, Nakagawa-Hattori Y, Kondo T, Mizuno Y (1992) Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson’s disease. J Neural Transm Park Dis Dement Sect 4(1):27–34PubMedCrossRefGoogle Scholar
  176. Yue M, Hinkle KM, Davies P, Trushina E, Fiesel FC, Christenson TA, Schroeder AS, Zhang L, Bowles E, Behrouz B, Lincoln SJ, Beevers JE, Milnerwood AJ, Kurti A, McLean PJ, Fryer JD, Springer W, Dickson DW, Farrer MJ, Melrose HL (2015) Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice. Neurobiol Dis 78:172–195.  https://doi.org/10.1016/j.nbd.2015.02.031 PubMedPubMedCentralCrossRefGoogle Scholar
  177. Zhang Z, Liu L, Jiang X, Zhai S, Xing D (2016) The essential role of Drp1 and its regulation by S-nitrosylation of parkin in dopaminergic neurodegeneration: implications for Parkinson’s disease. Antioxid Redox Signal 25(11):609–622.  https://doi.org/10.1089/ars.2016.6634 PubMedCrossRefGoogle Scholar
  178. Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, Eklund AC, Zhang-James Y, Kim PD, Hauser MA, Grunblatt E, Moran LB, Mandel SA, Riederer P, Miller RM, Federoff HJ, Wullner U, Papapetropoulos S, Youdim MB, Cantuti-Castelvetri I, Young AB, Vance JM, Davis RL, Hedreen JC, Adler CH, Beach TG, Graeber MB, Middleton FA, Rochet JC, Scherzer CR, Global PDGEC (2010) PGC-1alpha, a potential therapeutic target for early intervention in Parkinson’s disease. Sci Transl Med 2(52):52ra73.  https://doi.org/10.1126/scitranslmed.3001059 PubMedPubMedCentralCrossRefGoogle Scholar
  179. Zhu J, Wang KZ, Chu CT (2013) After the banquet: mitochondrial biogenesis, mitophagy, and cell survival. Autophagy 9(11):1663–1676.  https://doi.org/10.4161/auto.24135 PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.CNC – Center for Neuroscience and Cell BiologyUniversity of CoimbraCoimbraPortugal
  2. 2.Institute for Interdisciplinary ResearchUniversity of CoimbraCoimbraPortugal
  3. 3.Laboratory of Physiology, Faculty of MedicineUniversity of CoimbraCoimbraPortugal

Personalised recommendations