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Mitochondrial Proteins in the Development of Parkinson’s Disease

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Mitochondria in Health and in Sickness

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1158))

Abstract

Parkinson’s disease (PD) is a multifactorial disorder whose etiology is not completely understood. Strong evidences suggest that mitochondrial impairment and altered mitochondrial disposal play a key role in the development of this pathology. Here we show this association in both genetic and sporadic forms of the disease. Moreover, we describe the mitochondrial dysfunctions in toxin-induced models of PD, thus highlighting the importance of environmental factors in the onset of this pathology. In particular, we focus our attention on mitochondrial dynamics, mitochondrial biogenesis, and mitophagy and explain how their impairment could have a negative impact on dopaminergic neurons function and survival. Lastly, we aim at clarifying the important role played by proteomics in this field of research, proteomics being a global and unbiased approach suitable to unravel alterations of the molecular pathways in multifactorial diseases.

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Abbreviations

CCCP:

carbonyl cyanide m-chlorophenyl hydrazone

COR:

C-terminal of ROC

CREB:

cyclic AMP-responsive element-binding protein

DAT:

dopamine transporter

DRP1:

dynamin related protein 1

ERRs:

estrogen-related receptors

ETC:

electron transport chain

Fis1:

mitochondrial fission 1 protein

GCase:

β-glucocerebrosidase

Mff:

mitochondrial fission factor

MFNs:

mitofusins

MiD49:

mitochondrial dynamics protein MID49

MiD51:

mitochondrial dynamics protein MID51

MPP:

mitochondrial processing peptidase

MPP+:

1-methyl-4-phenylpyridinium

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

mtDNA:

mitochondrial DNA

MTERF1:

transcription termination factor 1

mtRNAP:

RNA polymerase

mtSSB:

mitochondrial single-stranded DNA-binding protein

NOS:

reactive nitrogen species

NRFs:

nuclear respiratory factors

OMA1:

metalloendopeptidase OMA1

OPA1:

dynamin-like 120 kDa protein

PARL:

presenilins-associated rhomboid-like protein

PD:

Parkinson’s disease

PGC-1α:

peroxisome proliferator-activated receptor gamma coactivator 1 alpha

PKA:

protein kinase A

POLG:

DNA polymerase γ

POLRMT:

DNA-directed RNA polymerase

PPAR:

peroxisome proliferator-activated receptor

PPP:

pentose phosphate pathway

ROC:

Ras of complex proteins

ROS:

reactive oxygen species

Tfam:

transcription factor A

TFB:

dimethyladenosine transferase 1

TIM:

translocase of inner mitochondrial membrane

TOM:

translocase of outer mitochondrial membrane

Top2α:

type IIA topoisomerase

VDACs:

voltage-dependent anion channels

YME1L:

ATP-dependent zinc metalloprotease YME1L1

α-syn:

α-synuclein

References

  1. Alberio T, Bondi H, Colombo F et al (2014) Mitochondrial proteomics investigation of a cellular model of impaired dopamine homeostasis, an early step in Parkinson’s disease pathogenesis. Mol Biosyst 10:1332–1344. https://doi.org/10.1039/c3mb70611g

    Article  CAS  PubMed  Google Scholar 

  2. Ascherio A, Schwarzschild MA (2016) The epidemiology of Parkinson’s disease: risk factors and prevention. Lancet Neurol 15:1257–1272. https://doi.org/10.1016/S1474-4422(16)30230-7

    Article  PubMed  Google Scholar 

  3. Au HC, Scheffler IE (1998) Promoter analysis of the human succinate dehydrogenase iron-protein gene. Both nuclear respiratory factors NRF-1 and NRF-2 are required. Eur J Biochem 251:164–174

    Article  CAS  PubMed  Google Scholar 

  4. Basso M, Giraudo S, Corpillo D et al (2004) Proteome analysis of human substantia nigra in Parkinson’s disease. Proteomics 4:3943–3952. https://doi.org/10.1002/pmic.200400848

    Article  CAS  PubMed  Google Scholar 

  5. Bekris LM, Mata IF, Zabetian CP (2010) The genetics of Parkinson disease. J Geriatr Psychiatry Neurol 23:228–242. https://doi.org/10.1177/0891988710383572

    Article  PubMed  PubMed Central  Google Scholar 

  6. Bender A, Krishnan KJ, Morris CM et al (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38:515–517. https://doi.org/10.1038/ng1769

    Article  CAS  PubMed  Google Scholar 

  7. Benskey MJ, Perez RG, Manfredsson FP (2016) The contribution of alpha synuclein to neuronal survival and function - Implications for Parkinson’s disease. J Neurochem 137:331–359. https://doi.org/10.1111/jnc.13570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Betarbet R, Sherer TB, MacKenzie G et al (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306. https://doi.org/10.1038/81834

    Article  CAS  PubMed  Google Scholar 

  9. Blesa JR, Prieto-Ruiz JA, Hernandez JM et al (2007) NRF-2 transcription factor is required for human TOMM20 gene expression. Gene 391:198–208. https://doi.org/10.1016/j.gene.2006.12.024

    Article  CAS  PubMed  Google Scholar 

  10. Blin O, Desnuelle C, Rascol O et al (1994) Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson’s disease and multiple system atrophy. J Neurol Sci 125:95–101

    Article  CAS  PubMed  Google Scholar 

  11. Bonawitz ND, Clayton DA, Shadel GS (2006) Initiation and beyond: multiple functions of the human mitochondrial transcription machinery. Mol Cell 24:813–825. https://doi.org/10.1016/j.molcel.2006.11.024

    Article  CAS  PubMed  Google Scholar 

  12. Bondi H, Zilocchi M, Mare MG et al (2016) Dopamine induces mitochondrial depolarization without activating PINK1-mediated mitophagy. J Neurochem 136:1219–1231. https://doi.org/10.1111/jnc.13506

    Article  CAS  PubMed  Google Scholar 

  13. Bonifati V, Rizzu P, van Baren MJ et al (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299:256–259. https://doi.org/10.1126/science.1077209

    Article  CAS  PubMed  Google Scholar 

  14. Bouzier-Sore AK, Bolanos JP (2015) Uncertainties in pentose-phosphate pathway flux assessment underestimate its contribution to neuronal glucose consumption: relevance for neurodegeneration and aging. Front. Aging Neurosci 7:89. https://doi.org/10.3389/fnagi.2015.00089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brooks AI, Chadwick CA, Gelbard HA et al (1999) Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 823:1–10

    Article  CAS  PubMed  Google Scholar 

  16. Burte F, De Girolamo LA, Hargreaves AJ et al (2011) Alterations in the mitochondrial proteome of neuroblastoma cells in response to complex 1 inhibition. J Proteome Res 10:1974–1986. https://doi.org/10.1021/pr101211k

    Article  CAS  PubMed  Google Scholar 

  17. Cali T, Ottolini D, Brini M (2013) Calcium and endoplasmic reticulum-mitochondria tethering in neurodegeneration. DNA Cell Biol 32:140–146. https://doi.org/10.1089/dna.2013.2011

    Article  CAS  PubMed  Google Scholar 

  18. Canet-Aviles RM, Wilson MA, Miller DW et al (2004) The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc. Natl. Acad. Sci. USA 101:9103–9108. https://doi.org/10.1073/pnas.0402959101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chan DC (2006a) Dissecting mitochondrial fusion. Dev Cell 11:592–594. https://doi.org/10.1016/j.devcel.2006.10.009

    Article  CAS  PubMed  Google Scholar 

  20. Chan DC (2006b) Mitochondria: dynamic organelles in disease, aging, and development. Cell 125:1241–1252. https://doi.org/10.1016/j.cell.2006.06.010

    Article  CAS  PubMed  Google Scholar 

  21. Chan P, DeLanney LE, Irwin I et al (1991) Rapid ATP loss caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mouse brain. J Neurochem 57:348–351

    Article  CAS  PubMed  Google Scholar 

  22. Chang DD, Clayton DA (1985) Priming of human mitochondrial DNA replication occurs at the light-strand promoter. Proc Natl Acad Sci U S A. 82:351–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chen H, Chan DC (2005) Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14 Spec 2:R283–R289. https://doi.org/10.1093/hmg/ddi270

    Article  Google Scholar 

  24. Chen H, Chan DC (2006) Critical dependence of neurons on mitochondrial dynamics. Curr Opin Cell Biol 18:453–459. https://doi.org/10.1016/j.ceb.2006.06.004

    Article  CAS  PubMed  Google Scholar 

  25. Chen Y, Dorn GW 2nd (2013) PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 340:471–475. https://doi.org/10.1126/science.1231031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chen H, Detmer SA, Ewald AJ et al (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160:189–200. https://doi.org/10.1083/jcb.200211046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chen H, Chomyn A, Chan DC (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280:26185–26192. https://doi.org/10.1074/jbc.M503062200

    Article  CAS  PubMed  Google Scholar 

  28. Chen H, McCaffery JM, Chan DC (2007) Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 130:548–562. https://doi.org/10.1016/j.cell.2007.06.026

    Article  CAS  PubMed  Google Scholar 

  29. Chiueh CC, Markey SP, Burns RS et al (1984) Neurochemical and behavioral effects of 1-methyl-4-phenyl-1,2,3,6-tet- rahydropyridine (MPTP) in rat, guinea pig, and monkey. Psychopharmacol Bull 20:548–553

    CAS  PubMed  Google Scholar 

  30. Choi BK, Kim JY, Cha MY et al (2015) beta-Amyloid and alpha-synuclein cooperate to block SNARE-dependent vesicle fusion. Biochemistry. 54:1831–1840. https://doi.org/10.1021/acs.biochem.5b00087

    Article  CAS  PubMed  Google Scholar 

  31. Chou AP, Li S, Fitzmaurice AG et al (2010) Mechanisms of rotenone-induced proteasome inhibition. Neurotoxicology 31:367–372. https://doi.org/10.1016/j.neuro.2010.04.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chu Y, Dodiya H, Aebischer P et al (2009) Alterations in lysosomal and proteasomal markers in Parkinson’s disease: relationship to alpha-synuclein inclusions. Neurobiol Dis. 35:385–398. https://doi.org/10.1016/j.nbd.2009.05.023

    Article  CAS  PubMed  Google Scholar 

  33. Chu Y, Morfini GA, Langhamer LB et al (2012) Alterations in axonal transport motor proteins in sporadic and experimental Parkinson’s disease. Brain 135:2058–2073. https://doi.org/10.1093/brain/aws133

    Article  PubMed  PubMed Central  Google Scholar 

  34. Chu Y, Goldman JG, Kelly L et al (2014) Abnormal alpha-synuclein reduces nigral voltage-dependent anion channel 1 in sporadic and experimental Parkinson’s disease. Neurobiol Dis. 69:1–14. https://doi.org/10.1016/j.nbd.2014.05.003

    Article  CAS  PubMed  Google Scholar 

  35. Cipolat S, Rudka T, Hartmann D et al (2006) Mitochondrial rhomboid PARL regulates cytochrome crelease during apoptosis via OPA1-dependent cristae remodeling. Cell 126:163–175. https://doi.org/10.1016/j.cell.2006.06.021

    Article  CAS  PubMed  Google Scholar 

  36. Cleeter MW, Chau KY, Gluck C et al (2013) Glucocerebrosidase inhibition causes mitochondrial dysfunction and free radical damage. Neurochem Int 62:1–7. https://doi.org/10.1016/j.neuint.2012.10.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cookson MR (2010) The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson’s disease. Nat Rev Neurosci 11:791–797. https://doi.org/10.1038/nrn2935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909

    Article  CAS  PubMed  Google Scholar 

  39. Davidzon G, Greene P, Mancuso M et al (2006) Early-onset familial parkinsonism due to POLG mutations. Ann Neurol 59:859–862. https://doi.org/10.1002/ana.20831

    Article  CAS  PubMed  Google Scholar 

  40. Davis GC, Williams AC, Markey SP et al (1979) Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res 1:249–254

    Article  CAS  PubMed  Google Scholar 

  41. de Brito OM, Scorrano L (2008) Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456:605–610. https://doi.org/10.1038/nature07534

    Article  CAS  PubMed  Google Scholar 

  42. Detmer SA, Chan DC (2007) Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations. J Cell Biol 176:405–414. https://doi.org/10.1083/jcb.200611080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Di Fonzo A, Rohé CF, Ferreira J et al (2005) A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson’s disease. Lancet. 365:412–415. https://doi.org/10.1016/S0140-6736(05)17829-5

    Article  CAS  PubMed  Google Scholar 

  44. Dias V, Junn E, Mouradian MM (2013) The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis 3:461–491. https://doi.org/10.3233/JPD-130230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Dimmer KS, Scorrano L (2006) (De)constructing mitochondria: what for? Physiology (Bethesda). 21:233–241. https://doi.org/10.1152/physiol.00010.2006

    Article  CAS  PubMed  Google Scholar 

  46. Djouadi F, Bastin J (2008) PPARs as therapeutic targets for correction of inborn mitochondrial fatty acid oxidation disorders. J Inherit Metab Dis 31:217–225. https://doi.org/10.1007/s10545-008-0844-7

    Article  CAS  PubMed  Google Scholar 

  47. Dunn L, Allen GF, Mamais A et al (2014) Dysregulation of glucose metabolism is an early event in sporadic Parkinson’s disease. Neurobiol Aging 35:1111–1115. https://doi.org/10.1016/j.neurobiolaging.2013.11.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Duty S, Jenner P (2011) Animal models of Parkinson’s disease: a source of noveltreatments and clues to the cause of the disease. Br J Pharmacol 164:1357–1391. https://doi.org/10.1111/j.1476-5381.2011.01426.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Egan DF, Shackelford DB, Mihaylova MM et al (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331:456–461. https://doi.org/10.1126/science.1196371

    Article  CAS  PubMed  Google Scholar 

  50. Eichner LJ, Giguère V (2011) Estrogen related receptors (ERRs): a new dawn in transcriptional control of mitochondrial gene networks. Mitochondrion 11:544–552. https://doi.org/10.1016/j.mito.2011.03.121

    Article  CAS  PubMed  Google Scholar 

  51. Eiyama A, Okamoto K (2015) PINK1/Parkin-mediated mitophagy in mammalian cells. Curr Opin Cell Biol 33:95–101. https://doi.org/10.1016/j.ceb.2015.01.002

    Article  CAS  PubMed  Google Scholar 

  52. Ekstrand MI, Falkenberg M, Rantanen A et al (2004) Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet 13:935–944. https://doi.org/10.1093/hmg/ddh109

    Article  CAS  PubMed  Google Scholar 

  53. Ekstrand MI, Terzioglu M, Galter D et al (2007) Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons. Proc Natl Acad Sci U S A 104:1325–1330. https://doi.org/10.1073/pnas.0605208103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Elbehti-Green A, Au HC, Mascarello JT et al (1998) Characterization of the human SDHC gene encoding of the integral membrane proteins of succinate-quinone oxidoreductase in mitochondria. Gene 213:133–140

    Article  CAS  PubMed  Google Scholar 

  55. Eura Y, Ishihara N, Yokota S et al (2003) Two mitofusin proteins, mammalian homologues of FZO, with distinct functions are both required for mitochondrial fusion. J Biochem 134:333–344

    Article  CAS  PubMed  Google Scholar 

  56. Exner N, Treske B, Paquet D et al (2007) Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci. 27:12413–12418. https://doi.org/10.1523/JNEUROSCI.0719-07.2007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Fabre E, Monserrat J, Herrero A et al (1999) Effect of MPTP on brain mitochondrial H2O2 and ATP production and on dopamine and DOPAC in the striatum. J Physiol Biochem 55:325–331

    CAS  PubMed  Google Scholar 

  58. Fernández-Moriano C, González-Burgos E, Gómez-Serranillos MP (2015) Mitochondria-Targeted Protective Compounds in Parkinson’s and Alzheimer’s Diseases. Oxid Med Cell Longev. 2015:408927. https://doi.org/10.1155/2015/408927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Fimia GM, Stoykova A, Romagnoli A et al (2007) Ambra1 regulates autophagy and development of the nervous system. Nature 447:1121–1125. https://doi.org/10.1038/nature05925

    Article  CAS  PubMed  Google Scholar 

  60. Fisher RP, Clayton DA (1988) Purification and characterization of human mitochondrial transcription factor 1. Mol Cell Biol 8:3496–3509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Fiskum G, Starkov A, Polster BM et al (2003) Mitochondrial mechanisms of neural cell death and neuroprotective interventions in Parkinson’s disease. Ann N Y Acad Sci 991:111–119

    Article  CAS  PubMed  Google Scholar 

  62. Forno LS, DeLanney LE, Irwin I et al (1993) Similarities and differences between MPTP-induced parkinsonsim and Parkinson’s disease. Neuropathologic considerations. Adv Neurol 60:600–608

    CAS  PubMed  Google Scholar 

  63. Fusté JM, Wanrooij S, Jemt E et al (2010) Mitochondrial RNA polymerase is needed for activation of the origin of light-strand DNA replication. Mol Cell 37:67–78. https://doi.org/10.1016/j.molcel.2009.12.021

    Article  CAS  PubMed  Google Scholar 

  64. Gao F, Chen D, Si J et al (2015) The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway. Hum Mol Genet 24:2528–2538. https://doi.org/10.1093/hmg/ddv017

    Article  CAS  PubMed  Google Scholar 

  65. Gasser T (2009) Molecular pathogenesis of Parkinson disease: insights from genetic studies. Expert Rev Mol Med. 11:e22. https://doi.org/10.1017/S1462399409001148

    Article  PubMed  Google Scholar 

  66. Gegg ME, Schapira AH (2016) Mitochondrial dysfunction associated with glucocerebrosidase deficiency. Neurobiol Dis 90:43–50. https://doi.org/10.1016/j.nbd.2015.09.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gegg ME, Cooper JM, Chau KY et al (2010) Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet 19:4861–4870. https://doi.org/10.1093/hmg/ddq419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Geisler S, Holmström KM, Skujat D et al (2010a) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12:119–131. https://doi.org/10.1038/ncb2012

    Article  CAS  PubMed  Google Scholar 

  69. Geisler S, Holmström KM, Treis A et al (2010b) The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations. Autophagy 6:871–878

    Article  CAS  PubMed  Google Scholar 

  70. Giasson BI, Lee VM (2001) Parkin and the molecular pathways of Parkinson’s disease. Neuron. 31:885–888

    Article  CAS  PubMed  Google Scholar 

  71. Gilks WP, Abou-Sleiman PM, Gandhi S et al (2005) A common LRRK2 mutation in idiopathic Parkinson’s disease. Lancet. 365:415–416. https://doi.org/10.1016/S0140-6736(05)17830-1

    Article  CAS  PubMed  Google Scholar 

  72. Gleyzer N, Vercauteren K, Scarpulla RC (2005) Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol 25:1354–1366. https://doi.org/10.1128/MCB.25.4.1354-1366.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Goo HG, Jung MK, Han SS et al (2013) HtrA2/Omi deficiency causes damage and mutation of mitochondrial DNA. Biochim Biophys Acta. 1833:1866–1875. https://doi.org/10.1016/j.bbamcr.2013.03.016

    Article  CAS  PubMed  Google Scholar 

  74. Graziewicz MA, Longley MJ, Copeland WC (2006) DNA polymerase gamma in mitochondrial DNA replication and repair. Chem Rev 106:383–405. https://doi.org/10.1021/cr040463d

    Article  CAS  PubMed  Google Scholar 

  75. Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629. https://doi.org/10.1126/science.1099320

    Article  CAS  PubMed  Google Scholar 

  76. Green DR, Galluzzi L, Kroemer G (2011) Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science 333:1109–1112. https://doi.org/10.1126/science.1201940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Guardia-Laguarta C, Area-Gomez E, Rüb C et al (2014) α-Synuclein is localized to mitochondria-associated ER membranes. J Neurosci. 34:249–259. https://doi.org/10.1523/JNEUROSCI.2507-13.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Haas RH, Nasirian F, Nakano K et al (1995) Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson’s disease. Ann Neurol. 37:714–722

    Article  CAS  PubMed  Google Scholar 

  79. Handschin C (2009) The biology of PGC-1α and its therapeutic potential. Trends Pharmacol Sci. 30:322–329. https://doi.org/10.1016/j.tips.2009.03.006

    Article  CAS  PubMed  Google Scholar 

  80. Hantraye P, Varastet M, Peschanski M et al (1993) Stable parkinsonian syndrome and uneven loss of striatal dopamine fibres following chronic MPTP administration in baboons. Neuroscience 53:169–178

    Article  CAS  PubMed  Google Scholar 

  81. Hayashi T, Ishimori C, Takahashi-Niki K et al (2009) DJ-1 binds to mitochondrial complex I and maintains its activity. Biochem Biophys Res Commun 390:667–672. https://doi.org/10.1016/j.bbrc.2009.10.025

    Article  CAS  PubMed  Google Scholar 

  82. Heo JY, Park JH, Kim SJ et al (2012) DJ-1 null dopaminergic neuronal cells exhibit defects in mitochondrial function and structure: involvement of mitochondrial complex I assembly. PLoS One 7:e32629. https://doi.org/10.1371/journal.pone.0032629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Herzig S, Long FX, Jhala US et al (2001) CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 413:179–183. https://doi.org/10.1038/35093131

    Article  CAS  PubMed  Google Scholar 

  84. Hirawake H, Taniwaki M, Tamura A et al (1999) Characterization of the human SDHD gene encoding the small subunit of cytochrome b (cybS) in mitochondrial succinate- ubiquinone oxidoreductase. Biochim Biophys Acta 1412:295–300

    Article  CAS  PubMed  Google Scholar 

  85. Hoang T, Choi DK, Nagai M et al (2009) Neuronal NOS and cyclooxygenase-2 contribute to DNA damage in a mouse model of Parkinson disease. Free Radic Biol Med 47:1049–1056. https://doi.org/10.1016/j.freeradbiomed.2009.07.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hoppins S, Lackner L, Nunnari J (2007) The machines that divide and fuse mitochondria. Annu Rev Biochem 76:751–780. https://doi.org/10.1146/annurev.biochem.76.071905.090048

    Article  CAS  PubMed  Google Scholar 

  87. Hung AY, Schwarzschild MA (2007) Clinical trials for neuroprotection in Parkinson’s disease: overcoming angst and futility? Curr Opin Neurol 20:477–483. https://doi.org/10.1097/WCO.0b013e32826388d6

    Article  CAS  PubMed  Google Scholar 

  88. Ingerman E, Perkins EM, Marino M et al (2005) Dnm1 forms spirals that are structurally tailored to fit mitochondria. J Cell Biol 170:1021–1027. https://doi.org/10.1083/jcb.200506078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ishihara N, Eura Y, Mihara K (2004) Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. J Cell Sci 117:6535–6546. https://doi.org/10.1242/jcs.01565

    Article  CAS  PubMed  Google Scholar 

  90. Ishihara N, Fujita Y, Oka T et al (2006) Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO J 25:2966–2977. https://doi.org/10.1038/sj.emboj.7601184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Itoh K, Nakamura K, Iijima M et al (2013) Mitochondrial dynamics in neurodegeneration. Trends Cell Biol 23:64–71. https://doi.org/10.1016/j.tcb.2012.10.006

    Article  CAS  PubMed  Google Scholar 

  92. Ivankovic D, Chau KY, Schapira AH et al (2016) Mitochondrial and lysosomal biogenesis are activated following PINK1/parkin-mediated mitophagy. J Neurochem 136:388–402. https://doi.org/10.1111/jnc.13412

    Article  CAS  PubMed  Google Scholar 

  93. Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79:368–376. https://doi.org/10.1136/jnnp.2007.131045

    Article  CAS  PubMed  Google Scholar 

  94. Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53(Suppl 3):S26–S36. https://doi.org/10.1002/ana.10483

    Article  CAS  PubMed  Google Scholar 

  95. Jenner P, Olanow CW (2006) The pathogenesis of cell death in Parkinson’s disease. Neurology. 66:S24–S36

    Article  PubMed  Google Scholar 

  96. Jin J, Meredith GE, Chen L et al (2005) Quantitative proteomic analysis of mitochondrial proteins: relevance to Lewy body formation and Parkinson’s disease. Brain Res Mol Brain Res 134:119–138. https://doi.org/10.1016/j.molbrainres.2004.10.003

    Article  CAS  PubMed  Google Scholar 

  97. Jin J, Hulette C, Wang Y et al (2006) Proteomic identification of a stress protein, mortalin/mthsp70/GRP75: relevance to Parkinson disease. Mol Cell Proteomics. 5:1193–1204. https://doi.org/10.1074/mcp.M500382-MCP200

    Article  CAS  PubMed  Google Scholar 

  98. Jin J, Davis J, Zhu D et al (2007) Identification of novel proteins affected by rotenone in mitochondria of dopaminergic cells. BMC Neurosci 8:67. https://doi.org/10.1186/1471-2202-8-67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Jin SM, Lazarou M, Wang C et al (2010) Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol 191:933–942. https://doi.org/10.1083/jcb.201008084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Jofuku A, Ishihara N, Mihara K (2005) Analysis of functional domains of rat mitochondrial Fis1, the mitochondrial fission-stimulating protein. Biochem Biophys Res Commun 333(2):650–659. https://doi.org/10.1016/j.bbrc.2005.05.154

    Article  CAS  PubMed  Google Scholar 

  101. Johnson ME, Bobrovskaya L (2015) An update on the rotenone models of Parkinson’s disease: their ability to reproduce the features of clinical disease and model gene-environment interactions. Neurotoxicology 46:101–116. https://doi.org/10.1016/j.neuro.2014.12.002

    Article  CAS  PubMed  Google Scholar 

  102. Jones GM, Vale JA (2000) Mechanisms of toxicity, clinical features, and management of diquat poisoning: a review. J Toxicol Clin Toxicol 38:123–128

    Article  CAS  PubMed  Google Scholar 

  103. Junn E, Jang WH, Zhao X et al (2009) Mitochondrial localization of DJ-1 leads to enhanced neuroprotection. J Neurosci Res 87:123–129. https://doi.org/10.1002/jnr.21831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Karren MA, Coonrod EM, Anderson TK et al (2005) The role of Fis1p-Mdv1p interactions in mitochondrial fission complex assembly. J Cell Biol 171:291–301. https://doi.org/10.1083/jcb.200506158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kim I, Rodriguez-Enriquez S, Lemasters JJ (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462:245–253. https://doi.org/10.1016/j.abb.2007.03.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Kitada T, Asakawa S, Hattori N et al (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608

    Article  CAS  PubMed  Google Scholar 

  107. Klein C, Westenberger A (2012) Genetics of Parkinson’s disease. Cold Spring Harb Perspect Med 2:a008888. https://doi.org/10.1101/cshperspect.a008888

    Article  PubMed  PubMed Central  Google Scholar 

  108. Korhonen JA, Gaspari M, Falkenberg M (2003) TWINKLE Has 5’ -> 3’ DNA helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein. J Biol Chem 278:48627–48632. https://doi.org/10.1074/jbc.M306981200

    Article  CAS  PubMed  Google Scholar 

  109. Koshiba T, Detmer SA, Kaiser JT (2004) Structural basis of mitochondrial tethering by mitofusin complexes. Science 305:858–862. https://doi.org/10.1126/science.1099793

    Article  CAS  PubMed  Google Scholar 

  110. Kruger R, Kuhn W, Muller T et al (1998) Ala30Pro mutation in the gene encoding alphasynuclein in Parkinson’s disease. Nature genetics 18:106–108

    Article  CAS  PubMed  Google Scholar 

  111. Kuroda Y, Mitsui T, Kunishige M et al (2006) Parkin enhances mitochondrial biogenesis in proliferating cells. Hum Mol Genet 15:883–895. https://doi.org/10.1093/hmg/ddl006

    Article  CAS  PubMed  Google Scholar 

  112. Langston JW, Ballard PA Jr (1983) Parkinson’s disease in a chemist working with 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. N Engl J Med 309:310

    CAS  PubMed  Google Scholar 

  113. Langston JW, Irwin I, Langston EB et al (1984) 1-Methyl-4-phenylpyr- idinium ion (MPP+): identification of a metabolite of MPTP, a toxin selective to the substantia nigra. Neuroscience Letters 48:87–92

    Article  CAS  PubMed  Google Scholar 

  114. Langston JW, Forno LS, Tetrud J et al (1999) Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann Neurol 46:598–605

    Article  CAS  PubMed  Google Scholar 

  115. Larsson NG, Wang J, Wilhelmsson H et al (1998) Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet 18:231–236. https://doi.org/10.1038/ng0398-231

    Article  CAS  PubMed  Google Scholar 

  116. Lee YJ, Jeong SY, Karbowski M et al (2004) Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Mol Biol Cell 15:5001–5011. https://doi.org/10.1091/mbc.E04-04-0294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Lee S, Sterky FH, Mourier A et al (2012) Mitofusin 2 is necessary for striatal axonal projections of midbrain dopamine neurons. Hum Mol Genet 21:4827–4835. https://doi.org/10.1093/hmg/dds352

    Article  CAS  PubMed  Google Scholar 

  118. Legesse-Miller A, Massol RH, Kirchhausen T (2003) Constriction and Dnm1p recruitment are distinct processes in mitochondrial fission. Mol Biol Cell 14:1953–1963. https://doi.org/10.1091/mbc.E02-10-0657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Lei S, Zavala-Flores L, Garcia-Garcia A et al (2014) Alterations in energy/redox metabolism induced by mitochondrial and environmental toxins: a specific role for glucose-6-phosphate-dehydrogenase and the pentose phosphate pathway in paraquat toxicity. ACS Chem Biol 9:2032–2048. https://doi.org/10.1021/cb400894a

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Lesage S, Brice A (2009) Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Hum Mol Genet 18:R48–R59. https://doi.org/10.1093/hmg/ddp012

    Article  CAS  PubMed  Google Scholar 

  121. Lim KL, Tan JM (2007) Role of the ubiquitin proteasome system in Parkinson’s disease. BMC Biochem 8(Suppl 1):S13. https://doi.org/10.1186/1471-2091-8-S1-S13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Lippolis R, Siciliano RA, Pacelli C et al (2015) Altered protein expression pattern in skin fibroblasts from parkin-mutant early-onset Parkinson’s disease patients. Biochim Biophys Acta 1852:1960–1970. https://doi.org/10.1016/j.bbadis.2015.06.015

    Article  CAS  PubMed  Google Scholar 

  123. Lücking CB, Dürr A, Bonifati V et al (2000) Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med 342:1560–1567. https://doi.org/10.1056/NEJM200005253422103

    Article  PubMed  Google Scholar 

  124. Luoma P, Melberg A, Rinne JO et al (2004) Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Lancet 364:875–882. https://doi.org/10.1016/S0140-6736(04)16983-3

    Article  CAS  PubMed  Google Scholar 

  125. Lutz AK, Exner N, Fett ME et al (2009) Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem 284:22938–22951. https://doi.org/10.1074/jbc.M109.035774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. MacVicar T, Langer T (2016) OPA1 processing in cell death and disease - the long and short of it. J Cell Sci 129:2297–2306. https://doi.org/10.1242/jcs.159186

    Article  CAS  PubMed  Google Scholar 

  127. Manning-Bog AB, Schüle B, Langston JW (2009) Alpha-synuclein-glucocerebrosidase interactions in pharmacological Gaucher models: a biological link between Gaucher disease and parkinsonism. Neurotoxicology. 30:1127–1132. https://doi.org/10.1016/j.neuro.2009.06.009

    Article  PubMed  Google Scholar 

  128. Markey SP, Johannessen JN, Chiueh CC et al (1984) Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 311:464–467

    Article  CAS  PubMed  Google Scholar 

  129. Martin I, Kim JW, Dawson VL et al (2014) LRRK2 pathobiology in Parkinson’s disease. J Neurochem 131:554–565. https://doi.org/10.1111/jnc.12949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Martinez A, Lectez B, Ramirez J et al (2017) Quantitative proteomic analysis of Parkin substrates in Drosophila neurons. Mol Neurodegener 12:29. https://doi.org/10.1186/s13024-017-0170-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Matsuda N, Sato S, Shiba K et al (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189:211–221. https://doi.org/10.1083/jcb.200910140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. McCormack AL, Di Monte DA (2003) Effects of L-dopa and other amino acids against paraquat-induced nigrostriatal degeneration. J Neurochem 85:82–86

    Article  CAS  PubMed  Google Scholar 

  133. McCormack AL, Thiruchelvam M, Manning-Bog AB et al (2002) Environmental risk factors and Parkinson’s disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 10:119–127

    Article  CAS  PubMed  Google Scholar 

  134. McFarland MA, Ellis CE, Markey SP et al (2008) Proteomics analysis identifies phosphorylation-dependent alpha-synuclein protein interactions. Mol Cell Proteomics 7:2123–2137. https://doi.org/10.1074/mcp.M800116-MCP200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Migdalska-Richards A, Schapira AH (2016) The relationship between glucocerebrosidase mutations and Parkinson disease. J Neurochem 139 Suppl 1:77–90. https://doi.org/10.1111/jnc.13385

    Article  CAS  PubMed  Google Scholar 

  136. Miralles Fusté J, Shi Y, Wanrooij S et al (2014) In vivo occupancy of mitochondrial single-stranded DNA binding protein supports the strand displacement mode of DNA replication. PLoS Genet 10:e1004832. https://doi.org/10.1371/journal.pgen.1004832

    Article  PubMed  PubMed Central  Google Scholar 

  137. Misko A, Jiang S, Wegorzewska I et al (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 30:4232–4240. https://doi.org/10.1523/JNEUROSCI.6248-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Monti C, Bondi H, Urbani A et al (2015) Systems biology analysis of the proteomic alterations induced by MPP(+), a Parkinson’s disease-related mitochondrial toxin. Front Cell Neurosci 9:14. https://doi.org/10.3389/fncel.2015.00014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Moors T, Paciotti S, Chiasserini D et al (2016) Lysosomal dysfunction and α-synuclein aggregation in Parkinson’s disease: diagnostic links. Mov Disord 31:791–801. https://doi.org/10.1002/mds.26562

    Article  CAS  PubMed  Google Scholar 

  140. Morais VA, Verstreken P, Roethig A et al (2009) Parkinson’s disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function. EMBO Mol Med 1:99–111. https://doi.org/10.1002/emmm.200900006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Mortiboys H, Johansen KK, Aasly JO et al (2010) Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2. Neurology 75:2017–2020. https://doi.org/10.1212/WNL.0b013e3181ff9685

    Article  CAS  PubMed  Google Scholar 

  142. Mozdy AD, McCaffery JM, Shaw JM (2000) Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J Cell Biol 151:367–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Muñoz P, Huenchuguala S, Paris I et al (2012) Dopamine oxidation and autophagy. Parkinsons Dis 2012:920953. https://doi.org/10.1155/2012/920953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Mytilineou C, Werner P, Molinari S et al (1994) Impaired oxidative decarboxylation of pyruvate in fibroblasts from patients with Parkinson’s disease. J Neural Transm Park Dis Dement Sect. 8:223–228

    Article  CAS  PubMed  Google Scholar 

  145. Nandipati S, Litvan I (2016) Environmental Exposures and Parkinson’s Disease. Int J Environ Res Public Health. 13:pii: E881. https://doi.org/10.3390/ijerph13090881

    Article  CAS  Google Scholar 

  146. Narendra D, Kane LA, Hauser DN et al (2010a) p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy 6:1090–1106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Narendra DP, Jin SM, Tanaka A et al (2010b) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8:e1000298. https://doi.org/10.1371/journal.pbio.1000298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Navarro-Yepes J, Anandhan A, Bradley E et al (2016) Inhibition of protein ubiquitination by paraquat and 1-methyl-4-phenylpyridinium impairs ubiquitin-dependent protein degradation pathways. Mol Neurobiol 53:5229–5251. https://doi.org/10.1007/s12035-015-9414-9

    Article  CAS  PubMed  Google Scholar 

  149. Neupert W (2016) Mitochondrial gene expression: a playground of evolutionary tinkering. Annu Rev Biochem 85:65–76. https://doi.org/10.1146/annurev-biochem-011116-110824

    Article  CAS  PubMed  Google Scholar 

  150. Nicklas WJ, Vyas I, Heikkila RE (1985) Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. Life Sciences 36:2503–2508

    Article  CAS  PubMed  Google Scholar 

  151. Nisoli E, Clementi E, Paolucci C et al (2003) Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299:896–899. https://doi.org/10.1126/science.1079368

    Article  CAS  PubMed  Google Scholar 

  152. Nisoli E, Falcone S, Tonello C et al (2004) Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals. Proc Natl Acad Sci USA 101:16507–16512. https://doi.org/10.1073/pnas.0405432101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Niu J, Yu M, Wang C et al (2012) Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin-like protein. J Neurochem 122:650–658. https://doi.org/10.1111/j.1471-4159.2012.07809.x

    Article  CAS  PubMed  Google Scholar 

  154. Okatsu K, Saisho K, Shimanuki M et al (2010) p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria. Genes Cells 15:887–900. https://doi.org/10.1111/j.1365-2443.2010.01426.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Olichon A, Baricault L, Gas N et al (2003) Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J Biol Chem 278:7743–7746. https://doi.org/10.1074/jbc.C200677200

    Article  CAS  PubMed  Google Scholar 

  156. Ongwijitwat S, Wong-Riley MT (2005) Is nuclear respiratory factor 2 a master transcriptional coordinator for all ten nuclear-encoded cy- tochrome c oxidase subunits in neurons? Gene 360:65–77. https://doi.org/10.1016/j.gene.2005.06.015

    Article  CAS  PubMed  Google Scholar 

  157. Ongwijitwat S, Liang HL, Graboyes EM et al (2006) Nuclear respiratory factor 2 senses changing cellular energy demands and its silencing down-regulates cytochrome oxidase and other target gene mRNAs. Gene 374:39–49. https://doi.org/10.1016/j.gene.2006.01.009

    Article  CAS  PubMed  Google Scholar 

  158. Ordureau A, Sarraf SA, Duda DM et al (2014) Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol Cell 56:360–375. https://doi.org/10.1016/j.molcel.2014.09.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Ossowska K, Wardas J, Smiałowska M et al (2005) A slowly developing dysfunction of dopaminergic nigrostriatal neurons induced by long-term paraquat administration in rats: an animal model of preclinical stages of Parkinson’s disease? Eur J Neurosci 22:1294–1304. https://doi.org/10.1111/j.1460-9568.2005.04301.x

    Article  CAS  PubMed  Google Scholar 

  160. Otera H, Mihara K (2011) Molecular mechanisms and physiologic functions of mitochondrial dynamics. J Biochem 149:241–251. https://doi.org/10.1093/jb/mvr002

    Article  CAS  PubMed  Google Scholar 

  161. Otera H, Wang C, Cleland MM et al (2010) Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J Cell Biol 191:1141–1158. https://doi.org/10.1083/jcb.201007152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Ottolini D, Calì T, Negro A et al (2013) The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering. Hum Mol Genet 22:2152–2168. https://doi.org/10.1093/hmg/ddt068

    Article  CAS  PubMed  Google Scholar 

  163. Ozgul S, Kasap M, Akpinar G et al (2015) Linking a compound-heterozygous Parkin mutant (Q311R and A371T) to Parkinson’s disease by using proteomic and molecular approaches. Neurochem Int 85-86:1–13. https://doi.org/10.1016/j.neuint.2015.03.007

    Article  CAS  PubMed  Google Scholar 

  164. Pacelli C, De Rasmo D, Signorile A et al (2011) Mitochondrial defect and PGC-1α dysfunction in parkin-associated familial Parkinson’s disease. Biochim Biophys Acta 1812:1041–1053. https://doi.org/10.1016/j.bbadis.2010.12.022

    Article  CAS  PubMed  Google Scholar 

  165. Palacino JJ, Sagi D, Goldberg MS et al (2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279:18614–18622

    Article  CAS  PubMed  Google Scholar 

  166. Pallanck LJ (2010) Culling sick mitochondria from the herd. J Cell Biol 191:1225–1227. https://doi.org/10.1083/jcb.201011068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Palmer CS, Osellame LD, Laine D et al (2011) MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep 12:565–573. https://doi.org/10.1038/embor.2011.54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Parihar MS, Parihar A, Fujita M et al (2008) Mitochondrial association of alpha-synuclein causes oxidative stress. Cell Mol Life Sci 65:1272–1284. https://doi.org/10.1007/s00018-008-7589-1

    Article  CAS  PubMed  Google Scholar 

  169. Parone PA, Da Cruz S, Tondera D et al (2008) Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA. PLoS One 3:e3257. https://doi.org/10.1371/journal.pone.0003257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Pennington K, Peng J, Hung CC et al (2010) Differential effects of wild-type and A53T mutant isoform of alpha-synuclein on the mitochondrial proteome of differentiated SH-SY5Y cells. J Proteome Res 9:2390–23401. https://doi.org/10.1021/pr901102d

    Article  CAS  PubMed  Google Scholar 

  171. Perier C, Tieu K, Guegan C et al (2005) Complex I deficiency primes Bax- dependent neuronal apoptosis through mitochondrial oxidative damage. Proc Natl Acad Sci U S A 102:19126–19131. https://doi.org/10.1073/pnas.0508215102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Perier C, Bove J, Wu DC et al (2007) Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson’s disease. Proc Natl Acad Sci U S A 104:8161–8166. https://doi.org/10.1073/pnas.0609874104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Periquet M, Corti O, Jacquier S et al (2005) Proteomic analysis of parkin knockout mice: alterations in energy metabolism, protein handling and synaptic function. J Neurochem 95:1259–1276. https://doi.org/10.1111/j.1471-4159.2005.03442.x

    Article  CAS  PubMed  Google Scholar 

  174. Pham AH, Meng S, Chu QN et al (2012) Loss of Mfn2 results in progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit. Hum Mol Genet 21:4817–4826. https://doi.org/10.1093/hmg/dds311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Piao Y, Kim HG, Oh MS et al (2012) Overexpression of TFAM, NRF-1 and myr-AKT protects the MPP(+)-induced mitochondrial dysfunctions in neuronal cells. Biochim Biophys Acta 1820:577–585. https://doi.org/10.1016/j.bbagen.2011.08.007

    Article  CAS  PubMed  Google Scholar 

  176. Pickrell AM, Youle RJ (2015) The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 85:257–273. https://doi.org/10.1016/j.neuron.2014.12.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Plun-Favreau H, Klupsch K, Moisoi N et al (2007) The mitochondrial protease HtrA2 is regulated by Parkinson’s disease-associated kinase PINK1. Nat Cell Biol 9:1243–1252. https://doi.org/10.1038/ncb1644

    Article  CAS  PubMed  Google Scholar 

  178. Polymeropoulos MH, Higgins JJ, Golbe LI et al (1996) Mapping of a gene for Parkinson’s disease to chromosome 4q21-q23. Science 274:1197–1199

    Article  CAS  PubMed  Google Scholar 

  179. Polymeropoulos MH, Lavedan C, Leroy E et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–2047

    Article  CAS  PubMed  Google Scholar 

  180. Poole AC, Thomas RE, Andrews LA et al (2008) The PINK1/parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 105:1638–1643. https://doi.org/10.1073/pnas.0709336105

    Article  PubMed  PubMed Central  Google Scholar 

  181. Prasad K, Winnik B, Thiruchelvam MJ et al (2007) Prolonged toxicokinetics and toxicodynamics of paraquat in mouse brain. Environ Health Perspect 115:1448–1453. https://doi.org/10.1289/ehp.9932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Przedborski S, Jackson-Lewis V, Yokoyama R et al (1996) Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity. Proc Natl Acad Sci U S A 93:4565–4571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24:78–90. https://doi.org/10.1210/er.2002-0012

    Article  CAS  PubMed  Google Scholar 

  184. Qi Y, Yan L, Yu C et al (2016) Structures of human mitofusin 1 provide insight into mitochondrial tethering. J Cell Biol 215:621–629. https://doi.org/10.1083/jcb.201609019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Ramonet D, Perier C, Recasens A et al (2013) Optic atrophy 1 mediates mitochondria remodeling and dopaminergic neurodegeneration linked to complex I deficiency. Cell Death Differ 20:77–85. https://doi.org/10.1038/cdd.2012.95

    Article  CAS  PubMed  Google Scholar 

  186. Ramsay RR, Salach JI, Dadgar J et al (1986) Inhibition of mitochondrial NADH dehydrogenase by pyridine derivatives and its possible relation to experimental and idiopathic parkinsonism. Biochem Biophys Res Commun 135:269–275

    Article  CAS  PubMed  Google Scholar 

  187. Reeve AK, Ludtmann MH, Angelova PR et al (2015) Aggregated α-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons. Cell Death Dis 6:e1820. https://doi.org/10.1038/cddis.2015.166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Richardson JR, Quan Y, Sherer TB et al (2005) Paraquat neurotoxicity is distinct from that of MPTP and rotenone. Toxicol Sci 88:193–201. https://doi.org/10.1093/toxsci/kfi304

    Article  CAS  PubMed  Google Scholar 

  189. Rojo M, Legros F, Chateau D et al (2002) Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J Cell Sci 115:1663–1674

    CAS  PubMed  Google Scholar 

  190. Saez-Atienzar S, Bonet-Ponce L, Blesa JR et al (2014) The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling. Cell Death Dis 5:e1368. https://doi.org/10.1038/cddis.2014.320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Sarraf SA, Raman M, Guarani-Pereira V et al (2013) Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 496:372–376. https://doi.org/10.1038/nature12043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Scarpulla RC (1999) Nuclear Transcription Factors in Cytochrome c and Cytochrome Oxidase Expression. In: Papa S, Guerrieri F, Tager JM (eds) Frontiers of Cellular Bioenergetics. Springer, Boston, MA, pp 553–591

    Chapter  Google Scholar 

  193. Scarpulla RC (2008) Transcriptional paradigms in Mammalian mitochondrial biogenesis and function. Physiol Rev 88:611–638. https://doi.org/10.1152/physrev.00025.2007

    Article  CAS  PubMed  Google Scholar 

  194. Scarpulla RC (2011) Nucleus-encoded regulators of mitochondrial function: integration of respiratory chain expression, nutrient sensing and metabolic stress. Biochim Biophys Acta 1819:1088–1097. https://doi.org/10.1016/j.bbagrm.2011.10.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Schapira AH (2015) Glucocerebrosidase and Parkinson disease: recent advances. Mol Cell Neurosci 66:37–42. https://doi.org/10.1016/j.mcn.2015.03.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Schapira AH, Jenner P (2011) Etiology and pathogenesis of Parkinson’s disease. Mov Disord. 26:1049–1055. https://doi.org/10.1002/mds.23732

    Article  PubMed  Google Scholar 

  197. Schapira AH, Cooper JM, Dexter D et al (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54:823–827

    Article  CAS  PubMed  Google Scholar 

  198. Scorrano L, Ashiya M, Buttle K et al (2002) A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev Cell 2:55–67

    Article  CAS  PubMed  Google Scholar 

  199. Shendelman S, Jonason A, Martinat C et al (2004) DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation. PLoS Biol 2:e362. https://doi.org/10.1371/journal.pbio.0020362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Sherer TB, Betarbet R, Greenamyre JT (2002a) Environment, mitochondria, and Parkinson’s disease. Neuroscientist. 8:192–197. https://doi.org/10.1177/1073858402008003004

    Article  CAS  PubMed  Google Scholar 

  201. Sherer TB, Betarbet R, Stout AK et al (2002b) An in vitro model of Parkinson’s disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci 22:7006–7015. doi: 20026721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Sherer TB, Kim JH, Betarbet R et al (2003) Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol 179:9–16

    Article  CAS  PubMed  Google Scholar 

  203. Shiba-Fukushima K, Imai Y, Yoshida S et al (2012) PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci Rep 2:1002. https://doi.org/10.1038/srep01002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Shimizu K, Ohtaki K, Matsubara K et al (2001) Carrier-mediated processes in blood—brain barrier penetration and neural uptake of paraquat. Brain Res 906:135–142

    Article  CAS  PubMed  Google Scholar 

  205. Shimizu K, Matsubara K, Ohtaki K et al (2003) Paraquat induces long-lasting dopamine overflow through the excitotoxic pathway in the striatum of freely moving rats. Brain Res 976:243–252

    Article  CAS  PubMed  Google Scholar 

  206. Shimura H, Hattori N, Kubo S et al (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25:302–305. https://doi.org/10.1038/77060

    Article  CAS  PubMed  Google Scholar 

  207. Shin JH, Ko HS, Kang H et al (2011) PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson’s disease. Cell 144:689–702. https://doi.org/10.1016/j.cell.2011.02.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Sim CH, Lio DS, Mok SS et al (2006) C-terminal truncation and Parkinson’s disease-associated mutations down-regulate the protein serine/threonine kinase activity of PTEN-induced kinase-1. Hum Mol Genet 365:412–415. https://doi.org/10.1093/hmg/ddl398

    Article  CAS  Google Scholar 

  209. Simon-Sanchez J, Singleton AB (2008) Sequencing analysis of OMI/HTRA2 shows previously reported pathogenic mutations in neurologically normal controls. Hum Molec Genet 17:1988–1993. https://doi.org/10.1093/hmg/ddn096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Singleton AB, Farrer M, Johnson J et al (2003) alpha-Synuclein locus triplication causes Parkinson’s disease. Science. 302:841. https://doi.org/10.1126/science.1090278

    Article  CAS  PubMed  Google Scholar 

  211. Singleton AB, Farrer MJ, Bonifati V (2013) The genetics of Parkinson’s disease: progress and therapeutic implications. Mov Disord 28:14–23. https://doi.org/10.1002/mds.25249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Song Z, Ghochani M, McCaffery JM et al (2009) Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion. Mol Biol Cell 20:3525–3532. https://doi.org/10.1091/mbc.E09-03-0252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Strappazzon F, Vietri-Rudan M, Campello S et al (2011) Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO J 30:1195–1208. https://doi.org/10.1038/emboj.2011.49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Strauss KM, Martins LM, Plun-Favreau H et al (2005) Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson’s disease. Hum Mol Genet 14:2099–2111. https://doi.org/10.1093/hmg/ddi215

    Article  CAS  PubMed  Google Scholar 

  215. 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

    Article  CAS  PubMed  Google Scholar 

  216. Sun M, Latourelle JC, Wooten GF et al (2006) Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study. Arch Neurol 63:826–832. https://doi.org/10.1001/archneur.63.6.826

    Article  PubMed  Google Scholar 

  217. Sun Y, Vashisht AA, Tchieu J et al (2012) Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy. J Biol Chem 287:40652–40660. https://doi.org/10.1074/jbc.M112.419721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Taira T, Saito Y, Niki T et al (2004) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5:213–218. https://doi.org/10.1038/sj.embor.7400074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Takahashi Y, Kako K, Arai H et al (2002) Characterization and identification of promoter elements in the mouse COX17 gene. Biochim Biophys Acta 1574:359–364

    Article  CAS  PubMed  Google Scholar 

  220. Tal MC, Sasai M, Lee HK et al (2009) Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci USA 106:2770–2775. https://doi.org/10.1073/pnas.0807694106

    Article  PubMed  PubMed Central  Google Scholar 

  221. Tanaka A, Cleland MM, Xu S et al (2010) Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol 191:1367–1380. https://doi.org/10.1083/jcb.201007013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Tanner CM, Kamel F, Ross GW et al (2011) Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect 119:866–872. https://doi.org/10.1289/ehp.1002839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Triplett JC, Zhang Z, Sultana R et al (2015) Quantitative expression proteomics and phosphoproteomics profile of brain from PINK1 knockout mice: insights into mechanisms of familial Parkinson’s disease. J Neurochem 133:750–765. https://doi.org/10.1111/jnc.13039

    Article  CAS  PubMed  Google Scholar 

  224. Truban D, Hou X, Caulfield TR et al (2017) PINK1, Parkin, and mitochondrial quality control: what can we learn about Parkinson’s disease pathobiology? J Parkinsons Dis 7:13–29. https://doi.org/10.3233/JPD-160989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Twig G, Hyde B, Shirihai OS (2008) Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. Biochim Biophys Acta 1777:1092–1097. https://doi.org/10.1016/j.bbabio.2008.05.001

    Article  CAS  PubMed  Google Scholar 

  226. Valente EM, Abou-Sleiman PM, Caputo V et al (2004a) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304:1158–1160. https://doi.org/10.1126/science.1096284

    Article  CAS  PubMed  Google Scholar 

  227. Valente EM, Salvi S, Ialongo T et al (2004b) PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann Neurol 56:336–341. https://doi.org/10.1002/ana.20256

    Article  CAS  PubMed  Google Scholar 

  228. Van Humbeeck C, Cornelissen T, Hofkens H et al (2011) Parkin interacts with Ambra1 to induce mitophagy. J Neurosci 31:10249–10261. https://doi.org/10.1523/JNEUROSCI.1917-11.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Van Laar VS, Dukes AA, Cascio M et al (2008) Proteomic analysis of rat brain mitochondria following exposure to dopamine quinone: implications for Parkinson disease. Neurobiol Dis 29:477–489. https://doi.org/10.1016/j.nbd.2007.11.007

    Article  CAS  PubMed  Google Scholar 

  230. Varastet M, Riche D, Maziere M (1994) Chronic MPTP treatment reproduces in baboons the differential vulnerability of mesencephalic dopami- nergic neurons observed in Parkinson’s disease. Neuroscience 63:47–56

    Article  CAS  PubMed  Google Scholar 

  231. Vekrellis K, Xilouri M, Emmanouilidou E et al (2011) Pathological roles of α-synuclein in neurological disorders. Lancet Neurol 10:1015–10125. https://doi.org/10.1016/S1474-4422(11)70213-7

    Article  CAS  PubMed  Google Scholar 

  232. Velayati A, Yu WH, Sidransky E (2010) The role of glucocerebrosidase mutations in Parkinson disease and Lewy body disorders. Curr Neurol Neurosci Rep 10:190–198. https://doi.org/10.1007/s11910-010-0102-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. Vila M, Przedborski S (2003) Targeting programmed cell death in neurodegenerative diseases. Nat Rev Neurosci 4:365–375. https://doi.org/10.1038/nrn1100

    Article  CAS  PubMed  Google Scholar 

  234. Villeneuve LM, Purnell PR, Boska MD et al (2016) Early Expression of Parkinson’s Disease-Related Mitochondrial Abnormalities in PINK1 Knockout Rats. Mol Neurobiol 53:171–186. https://doi.org/10.1007/s12035-014-8927-y

    Article  CAS  PubMed  Google Scholar 

  235. Virbasius JV, Scarpulla RC (1994) Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis. Proc Natl Acad Sci U S A 91:1309–1313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283:1482–1488

    Article  CAS  PubMed  Google Scholar 

  237. Wang X, Hai C (2016) Novel insights into redox system and the mechanism of redox regulation. Mol Biol Rep 43:607–628. https://doi.org/10.1007/s11033-016-4022-y

    Article  CAS  PubMed  Google Scholar 

  238. Wang G, Mao Z (2014) Chaperone-mediated autophagy: roles in neurodegeneration. Transl Neurodegener 3:20. https://doi.org/10.1186/2047-9158-3-20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Wang X, Winter D, Ashrafi G et al (2011a) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147:893–906. https://doi.org/10.1016/j.cell.2011.10.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Wang H, Song P, Du L et al (2011b) Parkin ubiquitinates Drp1 for proteasome-dependent degradation: implication of dysregulated mitochondrial dynamics in Parkinson disease. J Biol Chem 286:11649–11658. https://doi.org/10.1074/jbc.M110.144238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Wang X, Petrie TG, Liu Y et al (2012a) Parkinson’s disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction. J Neurochem 121:830–839. https://doi.org/10.1111/j.1471-4159.2012.07734.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  242. Wang X, Yan MH, Fujioka H et al (2012b) LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum Mol Genet 21:1931–1944. https://doi.org/10.1093/hmg/dds003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. Wareski P, Vaarmann A, Choubey V et al (2009) PGC-1{alpha} and PGC-1{beta} regulate mitochondrial density in neurons. J Biol Chem 284:21379–21385. https://doi.org/10.1074/jbc.M109.018911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Werner CJ, Heyny-von Haussen R, Mall G et al (2008) Proteome analysis of human substantia nigra in Parkinson’s disease. Proteome Sci 6:8. https://doi.org/10.1186/1477-5956-6-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. West AB, Moore DJ, Biskup S et al (2005) Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A 102:16842–16847. https://doi.org/10.1073/pnas.0507360102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Wu Z, Puigserver P, Andersson U et al (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98(1):115–124

    Article  CAS  PubMed  Google Scholar 

  247. Wu B, Song B, Tian S et al (2012) Central nervous system damage due to acute paraquat poisoning: a neuroimaging study with 3.0 T MRI. Neurotoxicology 33:1330–1337. https://doi.org/10.1016/j.neuro.2012.08.007

    Article  CAS  PubMed  Google Scholar 

  248. Xilouri M, Brekk OR, Stefanis L (2016) Autophagy and alpha-synuclein: relevance to Parkinson’s disease and related synucleopathies. Mov Disord 31:178–192. https://doi.org/10.1002/mds.26477

    Article  CAS  PubMed  Google Scholar 

  249. Xu R, Hu Q, Ma Q et al (2014) The protease Omi regulates mitochondrial biogenesis through the GSK3β/PGC-1α pathway. Cell Death Dis 5:e1373. https://doi.org/10.1038/cddis.2014.328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Xun Z, Sowell RA, Kaufman TC et al (2008) Quantitative proteomics of a presymptomatic A53T alpha-synuclein Drosophila model of Parkinson disease. Mol Cell Proteomics 7:1191–1203. https://doi.org/10.1074/mcp.M700467-MCP200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. Yang Y, Ouyang Y, Yang L et al (2008) Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc Natl Acad Sci U S A 105:7070–7075. https://doi.org/10.1073/pnas.0711845105

    Article  PubMed  PubMed Central  Google Scholar 

  252. Yoon Y, Krueger EW, Oswald BJ et al (2003) The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol 23:5409–5420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Youle RJ, Narendra DP (2011) Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 12:9–14. https://doi.org/10.1038/nrm3028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Yu W, Sun Y, Guo S et al (2011) The PINK1/Parkin pathway regulates mitochondrial dynamics and function in mammalian hippocampal and dopaminergic neurons. Hum Mol Genet 20:3227–3240. https://doi.org/10.1093/hmg/ddr235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Yumino K, Kawakami I, Tamura M et al (2002) Paraquat- and diquat-induced oxygen radical generation and lipid peroxidation in rat brain microsomes. J Biochem 131:565–570

    Article  CAS  PubMed  Google Scholar 

  256. Zanellati MC, Monti V, Barzaghi C (2015) Mitochondrial dysfunction in Parkinson disease: evidence in mutant PARK2 fibroblasts. Front Genet 6:78. https://doi.org/10.3389/fgene.2015.00078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Zarranz JJ, Alegre J, Gomez-Esteban JC et al (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Annals of neurology 55:164–173. https://doi.org/10.1093/hmg/ddr235

    Article  CAS  PubMed  Google Scholar 

  258. Zhang Y, Chan DC (2007) New insights into mitochondrial fusion. FEBS Lett 581:2168–2173. https://doi.org/10.1016/j.febslet.2007.01.095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  259. Zhang Y, Gao J, Chung KK et al (2000) Parkin functions as an E2-dependent ubiquitin–protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc Natl Acad Sci U S A 97:13354–13359. https://doi.org/10.1073/pnas.240347797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  260. Zhang X, Zhou JY, Chin MH et al (2010) Region-specific protein abundance changes in the brain of MPTP-induced Parkinson’s disease mouse model. J Proteome Res 9:1496–1509. https://doi.org/10.1021/pr901024z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  261. Zhang H, Zhang YW, Yasukawa T et al (2014) Increased negative supercoiling of mtDNA in TOP1mt knockout mice and presence of topoisomerases IIα and IIβ in vertebrate mitochondria. Nucleic Acids Res 42:7259–7267. https://doi.org/10.1093/nar/gku384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. Zilocchi M, Finzi G, Lualdi M et al (2018) Mitochondrial alterations in Parkinson’s disease human samples and cellular models. Neurochem Int 118:61–72. https://doi.org/10.1016/j.neuint.2018.04.013

    Article  CAS  PubMed  Google Scholar 

  263. Zimprich A, Biskup S, Leitner P et al (2004) Mutations in LRRK2 cause autosomal- dominant parkinsonism with pleomorphic pathology. Neuron 44:601–607. https://doi.org/10.1016/j.neuron.2004.11.005

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Canada

    Mara Zilocchi

  2. Department of Science and High Technology, University of Insubria, Busto Arsizio, VA, Italy

    Mauro Fasano & Tiziana Alberio

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  1. Institute of Biochemistry and Clinical Biochemistry, Università Cattolica del Sacro Cuore, Rome, Italy, Fondazione Policlinico Universitario A. Gemelli – IRCCS, Rome, Italy

    Andrea Urbani

  2. Department of Biochemistry, University of Regina, Regina, SK, Canada

    Mohan Babu

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Zilocchi, M., Fasano, M., Alberio, T. (2019). Mitochondrial Proteins in the Development of Parkinson’s Disease. In: Urbani, A., Babu, M. (eds) Mitochondria in Health and in Sickness. Advances in Experimental Medicine and Biology, vol 1158. Springer, Singapore. https://doi.org/10.1007/978-981-13-8367-0_2

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