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PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson’s disease

Ge, Preston, Dawson, Valina L., Dawson, Ted M.·2020·Molecular Neurodegeneration
DOI 10.1186/s13024-020-00367-7PMC PMC7071653
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Abstract

That certain cell types in the central nervous system are more likely to undergo neurodegeneration in Parkinson’s disease is a widely appreciated but poorly understood phenomenon. Many vulnerable subpopulations, including dopamine neurons in the substantia nigra pars compacta, have a shared phenotype of large, widely distributed axonal networks, dense synaptic connections, and high basal levels of neural activity. These features come at substantial bioenergetic cost, suggesting that these neurons experience a high degree of mitochondrial stress. In such a context, mechanisms of mitochondrial quality control play an especially important role in maintaining neuronal survival. In this review, we focus on understanding the unique challenges faced by the mitochondria in neurons vulnerable to neurodegeneration in Parkinson’s and summarize evidence that mitochondrial dysfunction contributes to disease pathogenesis and to cell death in these subpopulations. We then review mechanisms of mitochondrial quality control mediated by activation of PINK1 and Parkin, two genes that carry mutations associated with autosomal recessive Parkinson’s disease. We conclude by pinpointing critical gaps in our knowledge of PINK1 and Parkin function, and propose that understanding the connection between the mechanisms of sporadic Parkinson’s and defects in mitochondrial quality control will lead us to greater insights into the question of selective vulnerability.

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  1. Klein C, Westenberger A. Genetics of Parkinson's disease. Cold Spring Harb Perspect Med. 2012;2(1):a008888. · DOI
  2. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003;24(2):197–211. · DOI · Paper page
  3. Surmeier DJ, Obeso JA, Halliday GM. Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci. 2017;18(2):101–13. · DOI · Paper page
  4. Volpicelli-Daley LA, Luk KC, Patel TP, Tanik SA, Riddle DM, Stieber A, et al. Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron. 2011;72(1):57–71. · DOI · Paper page
  5. Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, et al. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012;338(6109):949–53. · DOI · Paper page
  6. Mao X, Ou MT, Karuppagounder SS, Kam TI, Yin X, Xiong Y, et al. Pathological alpha-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science. 2016;353:aah3374. · DOI · Paper page
  7. Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S, et al. Transneuronal propagation of pathologic alpha-Synuclein from the gut to the brain models Parkinson's disease. Neuron. 2019;103(4):627–41.e7. · DOI · Paper page
  8. Brundin P, Melki R. Prying into the prion hypothesis for Parkinson's disease. J Neurosci. 2017;37(41):9808–18. · DOI
  9. Giguere N, Burke Nanni S, Trudeau LE. On cell loss and selective vulnerability of neuronal populations in Parkinson's disease. Front Neurol. 2018;9:455. · DOI
  10. Bose A, Beal MF. Mitochondrial dysfunction in Parkinson's disease. J Neurochem. 2016;139(Suppl 1):216–31. · DOI
  11. Misgeld T, Schwarz TL. Mitostasis in neurons: maintaining mitochondria in an extended cellular architecture. Neuron. 2017;96(3):651–66. · DOI
  12. Grenier K, McLelland GL, Fon EA. Parkin- and PINK1-dependent Mitophagy in neurons: will the real pathway please stand up? Front Neurol. 2013;4:100. · DOI
  13. Spinelli JB, Haigis MC. The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018;20(7):745–54. · DOI · Paper page
  14. Scarffe LA, Stevens DA, Dawson VL, Dawson TM. Parkin and PINK1: much more than mitophagy. Trends Neurosci. 2014;37(6):315–24. · DOI · Paper page
  15. Amadoro G, Corsetti V, Florenzano F, Atlante A, Bobba A, Nicolin V, et al. Morphological and bioenergetic demands underlying the mitophagy in post-mitotic neurons: the pink-parkin pathway. Front Aging Neurosci. 2014;6:18. · DOI
  16. Kann O, Kovacs R. Mitochondria and neuronal activity. Am J Phys Cell Phys. 2007;292(2):C641–57. · DOI
  17. Bolam JP, Pissadaki EK. Living on the edge with too many mouths to feed: why dopamine neurons die. Mov Disord. 2012;27(12):1478–83. · DOI
  18. Moss J, Bolam JP. A dopaminergic axon lattice in the striatum and its relationship with cortical and thalamic terminals. J Neurosci. 2008;28(44):11221–30. · DOI
  19. Matsuda W, Furuta T, Nakamura KC, Hioki H, Fujiyama F, Arai R, et al. Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum. J Neurosci. 2009;29(2):444–53. · DOI · Paper page
  20. Anden NE, Hfuxe K, Hamberger B, Hokfelt T. A quantitative study on the nigro-neostriatal dopamine neuron system in the rat. Acta Physiol Scand. 1966;67(3):306–12. · DOI
  21. Pacelli C, Giguere N, Bourque MJ, Levesque M, Slack RS, Trudeau LE. Elevated mitochondrial bioenergetics and axonal Arborization size are key contributors to the vulnerability of dopamine neurons. Curr Biol. 2015;25(18):2349–60. · DOI
  22. Giguere N, Pacelli C, Saumure C, Bourque MJ, Matheoud D, Levesque D, et al. Comparative analysis of Parkinson's disease-associated genes in mice reveals altered survival and bioenergetics of Parkin-deficient dopamine neurons. J Biol Chem. 2018;293(25):9580–93. · DOI
  23. Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219(4587):979–80. · DOI · Paper page
  24. Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, et al. Rotenone, paraquat, and Parkinson's disease. Environ Health Perspect. 2011;119(6):866–72. · DOI
  25. Dhillon AS, Tarbutton GL, Levin JL, Plotkin GM, Lowry LK, Nalbone JT, et al. Pesticide/environmental exposures and Parkinson's disease in East Texas. J Agromedicine. 2008;13(1):37–48. · DOI
  26. Dawson TM, Dawson VL. Molecular pathways of neurodegeneration in Parkinson's disease. Science. 2003;302(5646):819–22. · DOI
  27. Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD. Mitochondrial complex I deficiency in Parkinson's disease. Lancet. 1989;1(8649):1269. · DOI
  28. Bindoff LA, Birch-Machin M, Cartlidge NE, Parker WD Jr, Turnbull DM. Mitochondrial function in Parkinson's disease. Lancet. 1989;2(8653):49. · DOI
  29. Giannoccaro MP, La Morgia C, Rizzo G, Carelli V. Mitochondrial DNA and primary mitochondrial dysfunction in Parkinson's disease. Mov Disord. 2017;32(3):346–63. · DOI
  30. Grunewald A, Rygiel KA, Hepplewhite PD, Morris CM, Picard M, Turnbull DM. Mitochondrial DNA depletion in respiratory chain-deficient Parkinson disease neurons. Ann Neurol. 2016;79(3):366–78. · DOI
  31. Coxhead J, Kurzawa-Akanbi M, Hussain R, Pyle A, Chinnery P, Hudson G. Somatic mtDNA variation is an important component of Parkinson's disease. Neurobiol Aging. 2016;38:217.e1–6. · DOI
  32. Dolle C, Flones I, Nido GS, Miletic H, Osuagwu N, Kristoffersen S, et al. Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease. Nat Commun. 2016;7:13548. · DOI
  33. Toulorge D, Schapira AH, Hajj R. Molecular changes in the postmortem parkinsonian brain. J Neurochem. 2016;139(Suppl 1):27–58. · DOI
  34. Navarro A, Boveris A, Bandez MJ, Sanchez-Pino MJ, Gomez C, Muntane G, et al. Human brain cortex: mitochondrial oxidative damage and adaptive response in Parkinson disease and in dementia with Lewy bodies. Free Radic Biol Med. 2009;46(12):1574–80. · DOI
  35. Deng H, Gao K, Jankovic J. The VPS35 gene and Parkinson's disease. Mov Disord. 2013;28(5):569–75. · DOI
  36. Braschi E, Goyon V, Zunino R, Mohanty A, Xu L, McBride HM. Vps35 mediates vesicle transport between the mitochondria and peroxisomes. Curr Biol. 2010;20(14):1310–5. · DOI
  37. Wang W, Wang X, Fujioka H, Hoppel C, Whone AL, Caldwell MA, et al. Parkinson's disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes. Nat Med. 2016;22(1):54–63. · DOI
  38. Tang FL, Liu W, Hu JX, Erion JR, Ye J, Mei L, et al. VPS35 deficiency or mutation causes dopaminergic neuronal loss by impairing mitochondrial fusion and function. Cell Rep. 2015;12(10):1631–43. · DOI
  39. Howlett EH, Jensen N, Belmonte F, Zafar F, Hu X, Kluss J, et al. LRRK2 G2019S-induced mitochondrial DNA damage is LRRK2 kinase dependent and inhibition restores mtDNA integrity in Parkinson's disease. Hum Mol Genet. 2017;26(22):4340–51. · DOI
  40. Ramonet D, Podhajska A, Stafa K, Sonnay S, Trancikova A, Tsika E, et al. PARK9-associated ATP13A2 localizes to intracellular acidic vesicles and regulates cation homeostasis and neuronal integrity. Hum Mol Genet. 2012;21(8):1725–43. · DOI
  41. Park JS, Koentjoro B, Veivers D, Mackay-Sim A, Sue CM. Parkinson's disease-associated human ATP13A2 (PARK9) deficiency causes zinc dyshomeostasis and mitochondrial dysfunction. Hum Mol Genet. 2014;23(11):2802–15. · DOI
  42. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392(6676):605–8. · DOI · Paper page
  43. Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang JW, et al. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A. 2006;103(28):10793–8. · DOI · Paper page
  44. Houlden H, Singleton AB. The genetics and neuropathology of Parkinson's disease. Acta Neuropathol. 2012;124(3):325–38. · DOI
  45. Doherty KM, Silveira-Moriyama L, Parkkinen L, Healy DG, Farrell M, Mencacci NE, et al. Parkin disease: a clinicopathologic entity? JAMA Neurol. 2013;70(5):571–9. · DOI
  46. Koros C, Simitsi A, Stefanis L. Genetics of Parkinson's disease: genotype-phenotype correlations. Int Rev Neurobiol. 2017;132:197–231. · DOI
  47. Schneider SA, Alcalay RN. Neuropathology of genetic synucleinopathies with parkinsonism: review of the literature. Mov Disord. 2017;32(11):1504–23. · DOI
  48. Harper JW, Ordureau A, Heo JM. Building and decoding ubiquitin chains for mitophagy. Nat Rev Mol Cell Biol. 2018;19(2):93–108. · DOI
  49. Rub C, Wilkening A, Voos W. Mitochondrial quality control by the Pink1/Parkin system. Cell Tissue Res. 2017;367(1):111–23. · DOI · Paper page
  50. Voigt A, Berlemann LA, Winklhofer KF. The mitochondrial kinase PINK1: functions beyond mitophagy. J Neurochem. 2016;139(Suppl 1):232–9. · DOI
  51. Rasool S, Soya N, Truong L, Croteau N, Lukacs GL, Trempe JF. PINK1 autophosphorylation is required for ubiquitin recognition. EMBO Rep. 2018;19:e44891. · DOI
  52. Trempe JF, Sauve V, Grenier K, Seirafi M, Tang MY, Menade M, et al. Structure of parkin reveals mechanisms for ubiquitin ligase activation. Science. 2013;340(6139):1451–5. · DOI · Paper page
  53. Ordureau A, Sarraf SA, Duda DM, Heo JM, Jedrychowski MP, Sviderskiy VO, et al. Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol Cell. 2014;56(3):360–75. · DOI
  54. Shiba-Fukushima K, Arano T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, et al. Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering. PLoS Genet. 2014;10(12):e1004861. · DOI
  55. Walinda E, Morimoto D, Sugase K, Shirakawa M. Dual function of Phosphoubiquitin in E3 activation of Parkin. J Biol Chem. 2016;291(32):16879–91. · DOI
  56. Ordureau A, Heo JM, Duda DM, Paulo JA, Olszewski JL, Yanishevski D, et al. Defining roles of PARKIN and ubiquitin phosphorylation by PINK1 in mitochondrial quality control using a ubiquitin replacement strategy. Proc Natl Acad Sci U S A. 2015;112(21):6637–42. · DOI · Paper page
  57. Tang MY, Vranas M, Krahn AI, Pundlik S, Trempe JF, Fon EA. Structure-guided mutagenesis reveals a hierarchical mechanism of Parkin activation. Nat Commun. 2017;8:14697. · DOI
  58. Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, et al. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature. 2014;510(7503):162–6. · DOI · Paper page
  59. Okatsu K, Koyano F, Kimura M, Kosako H, Saeki Y, Tanaka K, et al. Phosphorylated ubiquitin chain is the genuine Parkin receptor. J Cell Biol. 2015;209(1):111–28. · DOI
  60. Pao KC, Stanley M, Han C, Lai YC, Murphy P, Balk K, et al. Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation. Nat Chem Biol. 2016;12(5):324–31. · DOI
  61. Aguirre JD, Dunkerley KM, Mercier P, Shaw GS. Structure of phosphorylated UBL domain and insights into PINK1-orchestrated parkin activation. Proc Natl Acad Sci U S A. 2017;114(2):298–303. · DOI
  62. Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, et al. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature. 2013;496(7445):372–6. · DOI · Paper page
  63. Rose CM, Isasa M, Ordureau A, Prado MA, Beausoleil SA, Jedrychowski MP, et al. Highly multiplexed quantitative mass spectrometry analysis of Ubiquitylomes. Cell Syst. 2016;3(4):395–403.e4. · DOI
  64. Ko HS, von Coelln R, Sriram SR, Kim SW, Chung KK, Pletnikova O, et al. Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. J Neurosci. 2005;25(35):7968–78. · DOI
  65. Ko HS, Lee Y, Shin JH, Karuppagounder SS, Gadad BS, Koleske AJ, et al. Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function. Proc Natl Acad Sci U S A. 2010;107(38):16691–6. · DOI
  66. Imam SZ, Zhou Q, Yamamoto A, Valente AJ, Ali SF, Bains M, et al. Novel regulation of parkin function through c-Abl-mediated tyrosine phosphorylation: implications for Parkinson's disease. J Neurosci. 2011;31(1):157–63. · DOI · Paper page
  67. Lee Y, Karuppagounder SS, Shin JH, Lee YI, Ko HS, Swing D, et al. Parthanatos mediates AIMP2-activated age-dependent dopaminergic neuronal loss. Nat Neurosci. 2013;16(10):1392–400. · DOI · Paper page
  68. Wang Y, An R, Umanah GK, Park H, Nambiar K, Eacker SM, et al. A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1. Science. 2016;354:aad6872. · DOI · Paper page
  69. Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, et al. PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease. Cell. 2011;144(5):689–702. · DOI · Paper page
  70. Stevens DA, Lee Y, Kang HC, Lee BD, Lee YI, Bower A, et al. Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration. Proc Natl Acad Sci U S A. 2015;112(37):11696–701. · DOI
  71. Siddiqui A, Bhaumik D, Chinta SJ, Rane A, Rajagopalan S, Lieu CA, et al. Mitochondrial quality control via the PGC1alpha-TFEB signaling pathway is compromised by Parkin Q311X mutation but independently restored by rapamycin. J Neurosci. 2015;35(37):12833–44. · DOI
  72. Siddiqui A, Rane A, Rajagopalan S, Chinta SJ, Andersen JK. Detrimental effects of oxidative losses in parkin activity in a model of sporadic Parkinson's disease are attenuated by restoration of PGC1alpha. Neurobiol Dis. 2016;93:115–20. · DOI
  73. Cunningham CN, Baughman JM, Phu L, Tea JS, Yu C, Coons M, et al. USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria. Nat Cell Biol. 2015;17(2):160–9. · DOI
  74. Ordureau A, Paulo JA, Zhang W, Ahfeldt T, Zhang J, Cohn EF, et al. Dynamics of PARKIN-dependent mitochondrial Ubiquitylation in induced neurons and model systems revealed by digital snapshot proteomics. Mol Cell. 2018;70(2):211–27.e8. · DOI
  75. Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A. 2010;107(1):378–83. · DOI · Paper page
  76. Wong YC, Holzbaur EL. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci U S A. 2014;111(42):E4439–48. · DOI · Paper page
  77. Heo JM, Ordureau A, Paulo JA, Rinehart J, Harper JW. The PINK1-PARKIN mitochondrial Ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote Mitophagy. Mol Cell. 2015;60(1):7–20. · DOI · Paper page
  78. Yamano K, Wang C, Sarraf SA, Munch C, Kikuchi R, Noda NN, et al. Endosomal Rab cycles regulate Parkin-mediated mitophagy. Elife. 2018;7:e31326. · DOI
  79. Palikaras K, Lionaki E, Tavernarakis N. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nat Cell Biol. 2018;20(9):1013–22. · DOI
  80. Sung H, Tandarich LC, Nguyen K, Hollenbeck PJ. Compartmentalized regulation of Parkin-mediated mitochondrial quality control in the Drosophila nervous system in vivo. J Neurosci. 2016;36(28):7375–91. · DOI
  81. Van Laar VS, Arnold B, Cassady SJ, Chu CT, Burton EA, Berman SB. Bioenergetics of neurons inhibit the translocation response of Parkin following rapid mitochondrial depolarization. Hum Mol Genet. 2011;20(5):927–40. · DOI
  82. Cai Q, Zakaria HM, Simone A, Sheng ZH. Spatial parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons. Curr Biol. 2012;22(6):545–52. · DOI
  83. Seibler P, Graziotto J, Jeong H, Simunovic F, Klein C, Krainc D. Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells. J Neurosci. 2011;31(16):5970–6. · DOI
  84. McWilliams TG, Prescott AR, Allen GF, Tamjar J, Munson MJ, Thomson C, et al. Mito-QC illuminates mitophagy and mitochondrial architecture in vivo. J Cell Biol. 2016;214(3):333–45. · DOI
  85. Sun N, Yun J, Liu J, Malide D, Liu C, Rovira II, et al. Measuring in vivo Mitophagy. Mol Cell. 2015;60(4):685–96. · DOI
  86. Lee JJ, Sanchez-Martinez A, Zarate AM, Beninca C, Mayor U, Clague MJ, et al. Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin. J Cell Biol. 2018;217(5):1613–22. · DOI
  87. McWilliams TG, Prescott AR, Montava-Garriga L, Ball G, Singh F, Barini E, et al. Basal Mitophagy occurs independently of PINK1 in mouse tissues of high metabolic demand. Cell Metab. 2018;27(2):439–49.e5. · DOI · Paper page
  88. Kim YY, Um JH, Yoon JH, Kim H, Lee DY, Lee YJ, et al. Assessment of mitophagy in mt-Keima Drosophila revealed an essential role of the PINK1-Parkin pathway in mitophagy induction in vivo. FASEB J. 2019;33(9):9742–51. · DOI
  89. Cornelissen T, Vilain S, Vints K, Gounko N, Verstreken P, Vandenberghe W. Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila. Elife. 2018;7:e35878. · DOI · Paper page
  90. Vincow ES, Merrihew G, Thomas RE, Shulman NJ, Beyer RP, MacCoss MJ, et al. The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo. Proc Natl Acad Sci U S A. 2013;110(16):6400–5. · DOI · Paper page
  91. Devireddy S, Liu A, Lampe T, Hollenbeck PJ. The Organization of Mitochondrial Quality Control and Life Cycle in the nervous system in vivo in the absence of PINK1. J Neurosci. 2015;35(25):9391–401. · DOI
  92. Villa E, Marchetti S, Ricci JE. No Parkin zone: Mitophagy without Parkin. Trends Cell Biol. 2018;28(11):882–95. · DOI
  93. Maday S, Holzbaur EL. Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway. Dev Cell. 2014;30(1):71–85. · DOI · Paper page
  94. Brown MR, Sullivan PG, Geddes JW. Synaptic mitochondria are more susceptible to Ca2+overload than nonsynaptic mitochondria. J Biol Chem. 2006;281(17):11658–68. · DOI
  95. Naga KK, Sullivan PG, Geddes JW. High cyclophilin D content of synaptic mitochondria results in increased vulnerability to permeability transition. J Neurosci. 2007;27(28):7469–75. · DOI
  96. Davey GP, Canevari L, Clark JB. Threshold effects in synaptosomal and nonsynaptic mitochondria from hippocampal CA1 and paramedian neocortex brain regions. J Neurochem. 1997;69(6):2564–70. · DOI
  97. MacVicar TD, Lane JD. Impaired OMA1-dependent cleavage of OPA1 and reduced DRP1 fission activity combine to prevent mitophagy in cells that are dependent on oxidative phosphorylation. J Cell Sci. 2014;127(Pt 10):2313–25. · DOI
  98. van der Bliek AM, Shen Q, Kawajiri S. Mechanisms of mitochondrial fission and fusion. Cold Spring Harb Perspect Biol. 2013;5:a011072. · DOI
  99. Mishra P, Chan DC. Metabolic regulation of mitochondrial dynamics. J Cell Biol. 2016;212(4):379–87. · DOI
  100. Kageyama Y, Zhang Z, Roda R, Fukaya M, Wakabayashi J, Wakabayashi N, et al. Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. J Cell Biol. 2012;197(4):535–51. · DOI
  101. Pesah Y, Pham T, Burgess H, Middlebrooks B, Verstreken P, Zhou Y, et al. Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development. 2004;131(9):2183–94. · DOI
  102. Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A. 2008;105(5):1638–43. · DOI · Paper page
  103. Deng H, Dodson MW, Huang H, Guo M. The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A. 2008;105(38):14503–8. · DOI
  104. Park J, Lee G, Chung J. The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process. Biochem Biophys Res Commun. 2009;378(3):518–23. · DOI
  105. Yang Y, Ouyang Y, Yang L, Beal MF, McQuibban A, Vogel H, et al. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc Natl Acad Sci U S A. 2008;105(19):7070–5. · DOI
  106. Ziviani E, Tao RN, Whitworth AJ. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci U S A. 2010;107(11):5018–23. · DOI · Paper page
  107. Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AH, Taanman JW. Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet. 2010;19(24):4861–70. · DOI · Paper page
  108. Glauser L, Sonnay S, Stafa K, Moore DJ. Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1. J Neurochem. 2011;118(4):636–45. · DOI · Paper page
  109. Yu W, Sun Y, Guo S, Lu B. The PINK1/Parkin pathway regulates mitochondrial dynamics and function in mammalian hippocampal and dopaminergic neurons. Hum Mol Genet. 2011;20(16):3227–40. · DOI
  110. Rakovic A, Grunewald A, Kottwitz J, Bruggemann N, Pramstaller PP, Lohmann K, et al. Mutations in PINK1 and Parkin impair ubiquitination of Mitofusins in human fibroblasts. PLoS One. 2011;6(3):e16746. · DOI
  111. Yamada T, Murata D, Adachi Y, Itoh K, Kameoka S, Igarashi A, et al. Mitochondrial stasis reveals p62-mediated ubiquitination in Parkin-independent Mitophagy and mitigates nonalcoholic fatty liver disease. Cell Metab. 2018;28(4):588–604.e5. · DOI
  112. Buhlman L, Damiano M, Bertolin G, Ferrando-Miguel R, Lombes A, Brice A, et al. Functional interplay between Parkin and Drp1 in mitochondrial fission and clearance. Biochim Biophys Acta. 2014;1843(9):2012–26. · DOI
  113. Pryde KR, Smith HL, Chau KY, Schapira AH. PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy. J Cell Biol. 2016;213(2):163–71. · DOI · Paper page
  114. Burman JL, Pickles S, Wang C, Sekine S, Vargas JNS, Zhang Z, et al. Mitochondrial fission facilitates the selective mitophagy of protein aggregates. J Cell Biol. 2017;216(10):3231–47. · DOI · Paper page
  115. Abeliovich H, Zarei M, Rigbolt KT, Youle RJ, Dengjel J. Involvement of mitochondrial dynamics in the segregation of mitochondrial matrix proteins during stationary phase mitophagy. Nat Commun. 2013;4:2789. · DOI · Paper page
  116. Kolitsida P, Zhou J, Rackiewicz M, Nolic V, Dengjel J, Abeliovich H. Phosphorylation of mitochondrial matrix proteins regulates their selective mitophagic degradation. Proc Natl Acad Sci U S A. 2019;116(41):20517–27. · DOI
  117. Sugiura A, McLelland GL, Fon EA, McBride HM. A new pathway for mitochondrial quality control: mitochondrial-derived vesicles. EMBO J. 2014;33(19):2142–56. · DOI · Paper page
  118. Soubannier V, McLelland GL, Zunino R, Braschi E, Rippstein P, Fon EA, et al. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr Biol. 2012;22(2):135–41. · DOI
  119. McLelland GL, Soubannier V, Chen CX, McBride HM, Fon EA. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 2014;33(4):282–95.
  120. Matheoud D, Sugiura A, Bellemare-Pelletier A, Laplante A, Rondeau C, Chemali M, et al. Parkinson's disease-related proteins PINK1 and Parkin repress mitochondrial antigen presentation. Cell. 2016;166(2):314–27. · DOI · Paper page
  121. Abuaita BH, Schultz TL, O'Riordan MX. Mitochondria-derived vesicles deliver antimicrobial reactive oxygen species to control phagosome-localized Staphylococcus aureus. Cell Host Microbe. 2018;24(5):625–36.e5. · DOI · Paper page
  122. McLelland GL, Lee SA, McBride HM, Fon EA. Syntaxin-17 delivers PINK1/parkin-dependent mitochondrial vesicles to the endolysosomal system. J Cell Biol. 2016;214(3):275–91. · DOI
  123. Soubannier V, Rippstein P, Kaufman BA, Shoubridge EA, McBride HM. Reconstitution of mitochondria derived vesicle formation demonstrates selective enrichment of oxidized cargo. PLoS One. 2012;7(12):e52830. · DOI
  124. Matheoud D, Cannon T, Voisin A, Penttinen AM, Ramet L, Fahmy AM, et al. Intestinal infection triggers Parkinson's disease-like symptoms in Pink1(−/−) mice. Nature. 2019;571(7766):565–9. · DOI · Paper page
  125. Cadete VJ, Deschenes S, Cuillerier A, Brisebois F, Sugiura A, Vincent A, et al. Formation of mitochondrial-derived vesicles is an active and physiologically relevant mitochondrial quality control process in the cardiac system. J Physiol. 2016;594(18):5343–62. · DOI
  126. Finck BN, Kelly DP. PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest. 2006;116(3):615–22. · DOI
  127. Lee Y, Stevens DA, Kang SU, Jiang H, Lee YI, Ko HS, et al. PINK1 primes Parkin-mediated ubiquitination of PARIS in dopaminergic neuronal survival. Cell Rep. 2017;18(4):918–32. · DOI
  128. Zheng L, Bernard-Marissal N, Moullan N, D'Amico D, Auwerx J, Moore DJ, et al. Parkin functionally interacts with PGC-1alpha to preserve mitochondria and protect dopaminergic neurons. Hum Mol Genet. 2017;26(3):582–98.
  129. Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, et al. PGC-1alpha, a potential therapeutic target for early intervention in Parkinson's disease. Sci Transl Med. 2010;2(52):52ra73. · DOI
  130. Ciron C, Zheng L, Bobela W, Knott GW, Leone TC, Kelly DP, et al. PGC-1alpha activity in nigral dopamine neurons determines vulnerability to alpha-synuclein. Acta Neuropathol Commun. 2015;3:16. · DOI
  131. Clark J, Silvaggi JM, Kiselak T, Zheng K, Clore EL, Dai Y, et al. Pgc-1alpha overexpression downregulates Pitx3 and increases susceptibility to MPTP toxicity associated with decreased Bdnf. PLoS One. 2012;7(11):e48925. · DOI
  132. Ciron C, Lengacher S, Dusonchet J, Aebischer P, Schneider BL. Sustained expression of PGC-1alpha in the rat nigrostriatal system selectively impairs dopaminergic function. Hum Mol Genet. 2012;21(8):1861–76. · DOI
  133. St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, et al. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell. 2006;127(2):397–408. · DOI · Paper page
  134. Eschbach J, von Einem B, Muller K, Bayer H, Scheffold A, Morrison BE, et al. Mutual exacerbation of peroxisome proliferator-activated receptor gamma coactivator 1alpha deregulation and alpha-synuclein oligomerization. Ann Neurol. 2015;77(1):15–32. · DOI
  135. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, et al. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell. 2004;119(1):121–35. · DOI · Paper page
  136. Jiang H, Kang SU, Zhang S, Karuppagounder S, Xu J, Lee YK, et al. Adult Conditional Knockout of PGC-1alpha Leads to Loss of Dopamine Neurons. eNeuro. 2016;3:e0183–16.2016. · DOI
  137. McMeekin LJ, Li Y, Fox SN, Rowe GC, Crossman DK, Day JJ, et al. Cell-specific deletion of PGC-1alpha from medium spiny neurons causes transcriptional alterations and age-related motor impairment. J Neurosci. 2018;38(13):3273–86. · DOI
  138. Lesnik C, Golani-Armon A, Arava Y. Localized translation near the mitochondrial outer membrane: An update. RNA Biol. 2015;12(8):801–9. · DOI
  139. Chacinska A, Koehler CM, Milenkovic D, Lithgow T, Pfanner N. Importing mitochondrial proteins: machineries and mechanisms. Cell. 2009;138(4):628–44. · DOI
  140. Williams CC, Jan CH, Weissman JS. Targeting and plasticity of mitochondrial proteins revealed by proximity-specific ribosome profiling. Science. 2014;346(6210):748–51. · DOI · Paper page
  141. Zhang L, Shimoji M, Thomas B, Moore DJ, Yu SW, Marupudi NI, et al. Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis. Hum Mol Genet. 2005;14(14):2063–73. · DOI
  142. Gehrke S, Wu Z, Klinkenberg M, Sun Y, Auburger G, Guo S, et al. PINK1 and Parkin control localized translation of respiratory chain component mRNAs on mitochondria outer membrane. Cell Metab. 2015;21(1):95–108. · DOI
  143. Aschrafi A, Kar AN, Gale JR, Elkahloun AG, Vargas JN, Sales N, et al. A heterogeneous population of nuclear-encoded mitochondrial mRNAs is present in the axons of primary sympathetic neurons. Mitochondrion. 2016;30:18–23. · DOI
  144. Shigeoka T, Jung H, Jung J, Turner-Bridger B, Ohk J, Lin JQ, et al. Dynamic axonal translation in developing and mature visual circuits. Cell. 2016;166(1):181–92. · DOI
  145. Martinez A, Lectez B, Ramirez J, Popp O, Sutherland JD, Urbe S, et al. Quantitative proteomic analysis of Parkin substrates in Drosophila neurons. Mol Neurodegener. 2017;12(1):29. · DOI
  146. Jacoupy M, Hamon-Keromen E, Ordureau A, Erpapazoglou Z, Coge F, Corvol JC, et al. The PINK1 kinase-driven ubiquitin ligase Parkin promotes mitochondrial protein import through the presequence pathway in living cells. Sci Rep. 2019;9(1):11829. · DOI
  147. Bertolin G, Jacoupy M, Traver S, Ferrando-Miguel R, Saint Georges T, Grenier K, et al. Parkin maintains mitochondrial levels of the protective Parkinson's disease-related enzyme 17-beta hydroxysteroid dehydrogenase type 10. Cell Death Differ. 2015;22(10):1563–76. · DOI
  148. Muqit MM, Abou-Sleiman PM, Saurin AT, Harvey K, Gandhi S, Deas E, et al. Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress. J Neurochem. 2006;98(1):156–69. · DOI
  149. Schlossmacher MG, Frosch MP, Gai WP, Medina M, Sharma N, Forno L, et al. Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies. Am J Pathol. 2002;160(5):1655–67. · DOI
  150. LaVoie MJ, Ostaszewski BL, Weihofen A, Schlossmacher MG, Selkoe DJ. Dopamine covalently modifies and functionally inactivates parkin. Nat Med. 2005;11(11):1214–21. · DOI
  151. Lonskaya I, Hebron ML, Algarzae NK, Desforges N, Moussa CE. Decreased parkin solubility is associated with impairment of autophagy in the nigrostriatum of sporadic Parkinson's disease. Neuroscience. 2013;232:90–105. · DOI
  152. Chung KK, Thomas B, Li X, Pletnikova O, Troncoso JC, Marsh L, et al. S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function. Science. 2004;304(5675):1328–31. · DOI
  153. Sunico CR, Nakamura T, Rockenstein E, Mante M, Adame A, Chan SF, et al. S-Nitrosylation of parkin as a novel regulator of p53-mediated neuronal cell death in sporadic Parkinson's disease. Mol Neurodegener. 2013;8:29. · DOI
  154. Kurup PK, Xu J, Videira RA, Ononenyi C, Baltazar G, Lombroso PJ, et al. STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson's disease. Proc Natl Acad Sci U S A. 2015;112(4):1202–7. · DOI
  155. Fukae J, Sato S, Shiba K, Sato K, Mori H, Sharp PA, et al. Programmed cell death-2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson's disease. FEBS Lett. 2009;583(3):521–5. · DOI
  156. Yao D, Gu Z, Nakamura T, Shi ZQ, Ma Y, Gaston B, et al. Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity. Proc Natl Acad Sci U S A. 2004;101(29):10810–4. · DOI
  157. Wong ES, Tan JM, Wang C, Zhang Z, Tay SP, Zaiden N, et al. Relative sensitivity of parkin and other cysteine-containing enzymes to stress-induced solubility alterations. J Biol Chem. 2007;282(16):12310–8. · DOI
  158. Wang C, Ko HS, Thomas B, Tsang F, Chew KC, Tay SP, et al. Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin's protective function. Hum Mol Genet. 2005;14(24):3885–97. · DOI
  159. Brahmachari S, Lee S, Kim S, Yuan C, Karuppagounder SS, Ge P, et al. Parkin interacting substrate zinc finger protein 746 is a pathological mediator in Parkinson's disease. Brain. 2019;142(8):2380–401. · DOI
  160. Brahmachari S, Karuppagounder SS, Ge P, Lee S, Dawson VL, Dawson TM, et al. C-Abl and Parkinson's disease: mechanisms and therapeutic potential. J Park Dis. 2017;7(4):589–601.
  161. Liani E, Eyal A, Avraham E, Shemer R, Szargel R, Berg D, et al. Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease. Proc Natl Acad Sci U S A. 2004;101(15):5500–5. · DOI
  162. von Coelln R, Thomas B, Andrabi SA, Lim KL, Savitt JM, Saffary R, et al. Inclusion body formation and neurodegeneration are parkin independent in a mouse model of alpha-synucleinopathy. J Neurosci. 2006;26(14):3685–96. · DOI
  163. Lo Bianco C, Schneider BL, Bauer M, Sajadi A, Brice A, Iwatsubo T, et al. Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson's disease. Proc Natl Acad Sci U S A. 2004;101(50):17510–5. · DOI
  164. Petrucelli L, O'Farrell C, Lockhart PJ, Baptista M, Kehoe K, Vink L, et al. Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron. 2002;36(6):1007–19. · DOI
  165. Haywood AF, Staveley BE. Parkin counteracts symptoms in a Drosophila model of Parkinson's disease. BMC Neurosci. 2004;5:14. · DOI
  166. Yang Y, Nishimura I, Imai Y, Takahashi R, Lu B. Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Neuron. 2003;37(6):911–24. · DOI
  167. Mahul-Mellier AL, Fauvet B, Gysbers A, Dikiy I, Oueslati A, Georgeon S, et al. C-Abl phosphorylates alpha-synuclein and regulates its degradation: implication for alpha-synuclein clearance and contribution to the pathogenesis of Parkinson's disease. Hum Mol Genet. 2014;23(11):2858–79. · DOI
  168. Brahmachari S, Ge P, Lee SH, Kim D, Karuppagounder SS, Kumar M, et al. Activation of tyrosine kinase c-Abl contributes to alpha-synuclein-induced neurodegeneration. J Clin Invest. 2016;126(8):2970–88. · DOI
  169. Kawahara K, Hashimoto M, Bar-On P, Ho GJ, Crews L, Mizuno H, et al. Alpha-Synuclein aggregates interfere with Parkin solubility and distribution: role in the pathogenesis of Parkinson disease. J Biol Chem. 2008;283(11):6979–87. · DOI
  170. Chen J, Ren Y, Gui C, Zhao M, Wu X, Mao K, et al. Phosphorylation of Parkin at serine 131 by p38 MAPK promotes mitochondrial dysfunction and neuronal death in mutant A53T alpha-synuclein model of Parkinson's disease. Cell Death Dis. 2018;9(6):700. · DOI
  171. Fuzzati-Armentero MT, Cerri S, Blandini F. Peripheral-central Neuroimmune crosstalk in Parkinson's disease: what do patients and animal models tell us? Front Neurol. 2019;10:232. · DOI
  172. Singh K, Han K, Tilve S, Wu K, Geller HM, Sack MN. Parkin targets NOD2 to regulate astrocyte endoplasmic reticulum stress and inflammation. Glia. 2018;66(11):2427–37. · DOI
  173. Mouton-Liger F, Rosazza T, Sepulveda-Diaz J, Ieang A, Hassoun SM, Claire E, et al. Parkin deficiency modulates NLRP3 inflammasome activation by attenuating an A20-dependent negative feedback loop. Glia. 2018;66(8):1736–51. · DOI · Paper page
  174. Sun L, Shen R, Agnihotri SK, Chen Y, Huang Z, Bueler H. Lack of PINK1 alters glia innate immune responses and enhances inflammation-induced, nitric oxide-mediated neuron death. Sci Rep. 2018;8(1):383. · DOI
  175. Solano RM, Casarejos MJ, Menendez-Cuervo J, Rodriguez-Navarro JA. Garcia de Yebenes J, Mena MA. Glial dysfunction in parkin null mice: effects of aging. J Neurosci. 2008;28(3):598–611. · DOI
  176. Guzman JN, Sanchez-Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker PT, et al. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature. 2010;468(7324):696–700. · DOI
  177. Camello-Almaraz C, Gomez-Pinilla PJ, Pozo MJ, Camello PJ. Mitochondrial reactive oxygen species and Ca2+ signaling. Am J Phys Cell Phys. 2006;291(5):C1082–8. · DOI · Paper page

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Metadata

Authors
Ge, P., Dawson, V. L., & Dawson, T. M.
ORCID
Dawson, Ted M.
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2020-03-13
Volume
15
Issue
1
ISSN
1750-1326
DOI
10.1186/s13024-020-00367-7
PMC
PMC7071653
Cited by
496
References
26
Language
en
Licence
Funders
  • JPB Foundation (n/a)
  • National Institute of Neurological Disorders and Stroke (NS38377, NS097049)
  • National Institute on Aging (AG059686)
  • National Institute of General Medical Sciences (T32GM007753)
  • Adrienne Helis Malvin Medical Research Foundation (M-2014)
  • Diana Helis Henry Medical Research Foundation (H-1)

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