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Mitochondrial quality control by the Pink1/Parkin system

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Abstract

Mitochondrial dysfunction represents a prominent pathological feature in many neurodegenerative diseases, particularly in Parkinson’s disease (PD). Mutations in the genes encoding the proteins Pink1 and Parkin have been identified as genetic risk factors in familiar cases of PD. Research during the last decade has identified both proteins as crucial components of an organellar quality control system that contributes to the maintenance of mitochondrial function in healthy cells. The Pink1/Parkin system acts as a sensor for mitochondrial quality and is activated, in particular, after the loss of the electric potential across the inner mitochondrial membrane. Pink1 molecules accumulate at the surface of damaged mitochondria to recruit and activate Parkin, which, in turn, elicits a signaling pathway eventually leading to the autophagic removal of the damaged organelles. This review summarizes recent advances in our knowledge of the functional role of the Pink1/Parkin system in preventing the accumulation of damaged mitochondria by mitophagy.

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References

  • Aerts L, Craessaerts K, De Strooper B, Morais VA (2015) PINK1 kinase catalytic activity is regulated by phosphorylation on serines 228 and 402. J Biol Chem 290:2798–2811

    Article  CAS  PubMed  Google Scholar 

  • Ashrafi G, Schwarz TL (2013) The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ 20:31–42

    Article  CAS  PubMed  Google Scholar 

  • Ashrafi G, Schlehe JS, LaVoie MJ, Schwarz TL (2014) Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. J Cell Biol 206:655–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Becker D, Richter J, Tocilescu MA, Przedborski S, Voos W (2012) Pink1 kinase and its membrane potential (Deltapsi)-dependent cleavage product both localize to outer mitochondrial membrane by unique targeting mode. J Biol Chem 287:22969–22987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q, Foreman O, Kirkpatrick DS, Sheng M (2014) The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature 510:370–375

    CAS  PubMed  Google Scholar 

  • Chen Y, Dorn GW 2nd (2013) PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 340:471–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ciechanover A (2005) Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6:79–87

    Article  CAS  PubMed  Google Scholar 

  • Clague MJ, Urbe S (2010) Ubiquitin: same molecule, different degradation pathways. Cell 143:682–685

    Article  CAS  PubMed  Google Scholar 

  • Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441:1162–1166

    Article  CAS  PubMed  Google Scholar 

  • Deas E, Plun-Favreau H, Gandhi S, Desmond H, Kjaer S, Loh SH, Renton AE, Harvey RJ, Whitworth AJ, Martins LM, Abramov AY, Wood NW (2010) PINK1 cleavage at position A103 by the mitochondrial protease PARL. Hum Mol Genet 20:867–879

    Article  PubMed  PubMed Central  Google Scholar 

  • Deng H, Dodson MW, Huang H, Guo M (2008) The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A 105:14503–14508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duan X, Tong J, Xu Q, Wu Y, Cai F, Li T, Song W (2014) Upregulation of human PINK1 gene expression by NF-kB signalling. Mol Brain 7:57–67

    Article  PubMed  PubMed Central  Google Scholar 

  • Exner N, Treske B, Paquet D, Holmstrom K, Schiesling C, Gispert S, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Kruger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C (2007) Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci 27:12413–12418

    Article  CAS  PubMed  Google Scholar 

  • Fedorowicz MA, de Vries-Schneider RLA, Rüb C, Becker D, Huang Y, Zhou C, Wolken DMA, Voos W, Liu YH, Przedborski S (2014) Cytosolic cleaved PINK1 represses Parkin translocation to mitochondria and mitophagy. EMBO Rep 15:86–93

    Article  CAS  PubMed  Google Scholar 

  • Gautier CA, Kitada T, Shen J (2008) Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci U S A 105:11364–11369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AH, Taanman JW (2010) Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet 19:4861–4870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gehrke S, Wu Z, Klinkenberg M, Sun Y, Auburger G, Guo S, Lu B (2015) PINK1 and Parkin control localized translation of respiratory chain component mRNAs on mitochondria outer membrane. Cell Metab 21:95–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W (2010a) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12:119–131

    Article  CAS  PubMed  Google Scholar 

  • Geisler S, Holmstrom KM, Treis A, Skujat D, Weber SS, Fiesel FC, Kahle PJ, Springer W (2010b) The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations. Autophagy 6:871–878

    Article  CAS  PubMed  Google Scholar 

  • Gispert S, Ricciardi F, Kurz A, Azizov M, Hoepken HH, Becker D, Voos W, Leuner K, Muller WE, Kudin AP, Kunz WS, Zimmermann A, Roeper J, Wenzel D, Jendrach M, Garcia-Arencibia M, Fernandez-Ruiz J, Huber L, Rohrer H, Barrera M, Reichert AS, Rüb U, Chen A, Nussbaum RL, Auburger G (2009) Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. PLoS ONE 4:e5777

    Article  PubMed  PubMed Central  Google Scholar 

  • Glater EE, Megeath LJ, Stowers RS, Schwarz TL (2006) Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. J Cell Biol 173:545–557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomez-Sanchez R, Gegg ME, Bravo-San Pedro JM, Niso-Santano M, Alvarez-Erviti L, Pizarro-Estrella E, Gutierrez-Martin Y, Alvarez-Barrientos A, Fuentes JM, Gonzalez-Polo RA, Schapira AHV (2014) Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression. Neurobiol Dis 62:426–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Greene AW, Grenier K, Aguileta MA, Muise S, Farazifard R, Haque ME, McBride HM, Park DS, Fon EA (2012) Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep 13:378–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grenier K, McLelland GL, Fon EA (2013) Parkin- and PINK1-dependent mitophagy in neurons: will the real pathway please stand up? Front Neurol 4:100

    Article  PubMed  PubMed Central  Google Scholar 

  • Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97:1634–1658

    Article  CAS  PubMed  Google Scholar 

  • Haynes CM, Ron D (2010) The mitochondrial UPR—protecting organelle protein homeostasis. J Cell Sci 123:3849–3855

    Article  CAS  PubMed  Google Scholar 

  • Hoepken HH, Gispert S, Morales B, Wingerter O, Del Turco D, Mulsch A, Nussbaum RL, Muller K, Drose S, Brandt U, Deller T, Wirth B, Kudin AP, Kunz WS, Auburger G (2007) Mitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6. Neurobiol Dis 25:401–411

    Article  CAS  PubMed  Google Scholar 

  • Jin SM, Youle RJ (2013) The accumulation of misfolded proteins in the mitochondrial matrix is sensed by PINK1 to induce PARK2/Parkin-mediated mitophagy of polarized mitochondria. Autophagy 9:1750–1757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ (2010) Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol 191:933–942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamp F, Exner N, Lutz AK, Wender N, Hegermann J, Brunner B, Nuscher B, Bartels T, Giese A, Beyer K, Eimer S, Winklhofer KF, Haass C (2010) Inhibition of mitochondrial fusion by alpha-synuclein is rescued by PINK1, Parkin and DJ-1. EMBO J 29:3571–3589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, Banerjee S, Youle RJ (2014) PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol 205:143–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanki T, Klionsky DJ (2010) The molecular mechanism of mitochondria autophagy in yeast. Mol Microbiol 75:795–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS, Hofmann K, Alessi DR, Knebel A, Trost M, Muqit MMK (2014) Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser(65). Biochem J 460:127–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirkin V, Lamark T, Johansen T, Dikic I (2009) NBR1 cooperates with p62 in selective autophagy of ubiquitinated targets. Autophagy 5:732–733

    Article  CAS  PubMed  Google Scholar 

  • Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile Parkinsonism. Nature 392:605–608

    Article  CAS  PubMed  Google Scholar 

  • Klein C, Westenberger A (2012) Genetics of Parkinson’s disease. Cold Spring Harb Perspect Med 2:a008888

    Article  PubMed  PubMed Central  Google Scholar 

  • Klinkenberg M, Gispert S, Dominguez-Bautista JA, Braun I, Auburger G, Jendrach M (2012) Restriction of trophic factors and nutrients induces PARKIN expression. Neurogenetics 13:9–21

    Article  CAS  PubMed  Google Scholar 

  • Kondapalli C, Kazlauskaite A, Zhang N, Woodroof HI, Campbell DG, Gourlay R, Burchell L, Walden H, Macartney TJ, Deak M, Knebel A, Alessi DR, Muqit MM (2012) PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol 2:120080

    Article  PubMed  PubMed Central  Google Scholar 

  • Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, Kimura Y, Tsuchiya H, Yoshihara H, Hirokawa T, Endo T, Fon EA, Trempe JF, Saeki Y, Tanaka K, Matsuda N (2014) Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510:162–166

    CAS  PubMed  Google Scholar 

  • Lazarou M, Jin SM, Kane LA, Youle RJ (2012) Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin. Dev Cell 22:320–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, Sideris DP, Fogel AI, Youle RJ (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524:309–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin W, Kang UJ (2008) Characterization of PINK1 processing, stability, and subcellular localization. J Neurochem 106:464–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lutz AK, Exner N, Fett ME, Schlehe JS, Kloos K, Lammermann K, Brunner B, Kurz-Drexler A, Vogel F, Reichert AS, Bouman L, Vogt-Weisenhorn D, Wurst W, Tatzelt J, Haass C, Winklhofer KF (2009) Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem 284:22938–22951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, Sou YS, Saiki S, Kawajiri S, Sato F, Kimura M, Komatsu M, Hattori N, Tanaka K (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189:211–221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mei Y, Zhang Y, Yamamoto K, Xie W, Mak TW, You H (2009) FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation. Proc Natl Acad Sci U S A 106:5153–5158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muqit MM, Abou-Sleiman PM, Saurin AT, Harvey K, Gandhi S, Deas E, Eaton S, Payne Smith MD, Venner K, Matilla A, Healy DG, Gilks WP, Lees AJ, Holton J, Revesz T, Parker PJ, Harvey RJ, Wood NW, Latchman DS (2006) Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress. J Neurochem 98:156–169

    Article  CAS  PubMed  Google Scholar 

  • Murata H, Takamatsu H, Liu S, Kataoka K, Huh NH, Sakaguchi M (2015) NRF2 regulates PINK1 expression under oxidative stress conditions. PLoS ONE 10:e0142438

    Article  PubMed  PubMed Central  Google Scholar 

  • Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183:795–803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8:e1000298

    Article  PubMed  PubMed Central  Google Scholar 

  • Ni HM, Williams JA, Ding WX (2015) Mitochondrial dynamics and mitochondrial quality control. Redox Biol 4:6–13

    Article  CAS  PubMed  Google Scholar 

  • Okamoto K, Kondo-Okamoto N, Ohsumi Y (2009) Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev Cell 17:87–97

    Article  CAS  PubMed  Google Scholar 

  • Okatsu K, Oka T, Iguchi M, Imamura K, Kosako H, Tani N, Kimura M, Go E, Koyano F, Funayama M, Shiba-Fukushima K, Sato S, Shimizu H, Fukunaga Y, Taniguchi H, Komatsu M, Hattori N, Mihara K, Tanaka K, Matsuda N (2012) PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat Commun 3:1016

    Article  PubMed  PubMed Central  Google Scholar 

  • Ordureau A, Sarraf SA, Duda DM, Heo JM, Jedrychowski MP, Sviderskiy VO, Olszewski JL, Koerber JT, Xie T, Beausoleil SA, Wells JA, Gygi SP, Schulman BA, Harper JW (2014) Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol Cell 56:360–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282:24131–24145

    Article  CAS  PubMed  Google Scholar 

  • Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM, Chung J (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441:1157–1161

    Article  CAS  PubMed  Google Scholar 

  • Pickrell AM, Youle RJ (2015) The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 85:257–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plun-Favreau H, Klupsch K, Moisoi N, Gandhi S, Kjaer S, Frith D, Harvey K, Deas E, Harvey RJ, McDonald N, Wood NW, Martins LM, Downward J (2007) The mitochondrial protease HtrA2 is regulated by Parkinson’s disease-associated kinase PINK1. Nat Cell Biol 9:1243–1252

    Article  CAS  PubMed  Google Scholar 

  • Pridgeon JW, Olzmann JA, Chin L-S, Li L (2007) PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. PLoS Biol 5:1494–1503

    Article  CAS  Google Scholar 

  • Priyadarshini M, Orosco LA, Panula PJ (2013) Oxidative stress and regulation of Pink1 in zebrafish (Danio rerio). PLoS ONE 8:e81851

    Article  PubMed  PubMed Central  Google Scholar 

  • Pryde KR, Smith HL, Chau KY, Schapira AH (2016) PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy. J Cell Biol 213:163–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quiros PM, Mottis A, Auwerx J (2016) Mitonuclear communication in homeostasis and stress. Nat Rev Mol Cell Biol 17:213–226

    Article  CAS  PubMed  Google Scholar 

  • Riley BE, Lougheed JC, Callaway K, Velasquez M, Brecht E, Nguyen L, Shaler T, Walker D, Yang Y, Regnstrom K, Diep L, Zhang Z, Chiou S, Bova M, Artis DR, Yao N, Baker J, Yednock T, Johnston JA (2013) Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases. Nat Commun 4:1982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rüb C, Schröder N, Voos W (2015) Biochemical properties of the kinase PINK1 as sensor protein for mitochondrial damage signalling. Biochem Soc Trans 43:287–291

    Article  PubMed  Google Scholar 

  • Sakurai M, Kawamura T, Nishimura H, Suzuki H, Tezuka F, Abe K (2009) Induction of Parkinson disease-related proteins in motor neurons after transient spinal cord ischemia in rabbits. J Cereb Blood Flow Metab 29:752–758

    Article  CAS  PubMed  Google Scholar 

  • Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW (2013) Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 496:372–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulz C, Schendzielorz A, Rehling P (2015) Unlocking the presequence import pathway. Trends Cell Biol 25:265–275

    Article  CAS  PubMed  Google Scholar 

  • Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, Kundu M, Opferman JT, Cleveland JL, Miller JL, Ney PA (2007) NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci U S A 104:19500–19505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi J, Fung G, Deng H, Zhang J, Fiesel FC, Springer W, Li X, Luo H (2015) NBR1 is dispensable for PARK2-mediated mitophagy regardless of the presence or absence of SQSTM1. Cell Death Dis 6:e1943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shiba-Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, Hattori N (2012) PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci Rep 2:1002

    Article  PubMed  PubMed Central  Google Scholar 

  • Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G (2005) Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14:3477–3492

    Article  CAS  PubMed  Google Scholar 

  • Slobodkin MR, Elazar Z (2013) The Atg8 family: multifunctional ubiquitin-like key regulators of autophagy. Essays Biochem 55:51–64

    Article  CAS  PubMed  Google Scholar 

  • Smit JJ, Monteferrario D, Noordermeer SM, van Dijk WJ, van der Reijden BA, Sixma TK (2012) The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension. EMBO J 31:3833–3844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stieglitz B, Morris-Davies AC, Koliopoulos MG, Christodoulou E, Rittinger K (2012) LUBAC synthesizes linear ubiquitin chains via a thioester intermediate. EMBO Rep 13:840–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11:621–632

    Article  CAS  PubMed  Google Scholar 

  • Takatori S, Ito G, Iwatsubo T (2008) Cytoplasmic localization and proteasomal degradation of N-terminally cleaved form of PINK1. Neurosci Lett 430:13–17

    Article  CAS  PubMed  Google Scholar 

  • Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, Youle RJ (2010) Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol 191:1367–1380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomas RE, Andrews LA, Burman JL, Lin WY, Pallanck LJ (2014) PINK1-Parkin pathway activity is regulated by degradation of PINK1 in the mitochondrial matrix. PLoS Genet 10:e1004279

    Article  PubMed  PubMed Central  Google Scholar 

  • Trempe JF, Fon EA (2013) Structure and function of Parkin, PINK1, and DJ-1, the Three Musketeers of Neuroprotection. Front Neurol 4:38

    Article  PubMed  PubMed Central  Google Scholar 

  • Trempe JF, Sauve V, Grenier K, Seirafi M, Tang MY, Menade M, Al-Abdul-Wahid S, Krett J, Wong K, Kozlov G, Nagar B, Fon EA, Gehring K (2013) Structure of parkin reveals mechanisms for ubiquitin ligase activation. Science 340:1451–1455

    Article  CAS  PubMed  Google Scholar 

  • Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304:1158–1160

    Article  CAS  PubMed  Google Scholar 

  • Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magrane J, Moore DJ, Dawson VL, Grailhe R, Dawson TM, Li C, Tieu K, Przedborski S (2010) PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A 107:378–383

    Article  CAS  PubMed  Google Scholar 

  • Voos W (2013) Chaperone-protease networks in mitochondrial protein homeostasis. Biochim Biophys Acta 1833:388–399

    Article  CAS  PubMed  Google Scholar 

  • Wang K, Klionsky DJ (2011) Mitochondria removal by autophagy. Autophagy 7:297–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, LaVoie MJ, Schwarz TL (2011) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147:893–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wauer T, Komander D (2013) Structure of the human Parkin ligase domain in an autoinhibited state. EMBO J 32:2099–3112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wenzel DM, Lissounov A, Brzovic PS, Klevit RE (2011) UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474:105–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winklhofer KF (2014) Parkin and mitochondrial quality control: toward assembling the puzzle. Trends Cell Biol 24:332–341

    Article  CAS  PubMed  Google Scholar 

  • Wong YC, Holzbaur EL (2014) 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 111:E4439–E4448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wood-Kaczmar A, Gandhi S, Yao Z, Abramov AS, Miljan EA, Keen G, Stanyer L, Hargreaves I, Klupsch K, Deas E, Downward J, Mansfield L, Jat P, Taylor J, Heales S, Duchen MR, Latchman D, Tabrizi SJ, Wood NW (2008) PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons. PLoS ONE 3:e2455

    Article  PubMed  PubMed Central  Google Scholar 

  • Yoshii SR, Mizushima N (2015) Autophagy machinery in the context of mammalian mitophagy. Biochim Biophys Acta 1853:2797–2801

    Article  CAS  PubMed  Google Scholar 

  • Youle RJ, van der Bliek AM (2012) Mitochondrial fission, fusion, and stress. Science 337:1062–1065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Youle RJ, Narendra DP (2011) Mechanisms of mitophagy. Nat Rev Mol Cell Biol 12:9–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng XD, Hunter T (2014) Pink1, the first ubiquitin kinase. EMBO J 33:1621–1623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou C, Huang Y, Shao Y, May J, Prou D, Perier C, Dauer W, Schon EA, Przedborski S (2008) The kinase domain of mitochondrial PINK1 faces the cytoplasm. Proc Natl Acad Sci U S A 105:12022–12027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ziviani E, Tao RN, Whitworth AJ (2010) Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci U S A 107:5018–5023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Institut für Biochemie und Molekularbiologie (IBMB), Universität Bonn, Nussallee 11, 53115, Bonn, Germany

    Cornelia Rüb, Anne Wilkening & Wolfgang Voos

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  1. Cornelia Rüb
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  2. Anne Wilkening
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  3. Wolfgang Voos
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Correspondence to Wolfgang Voos.

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The work was supported by a grant from the Deutsche Forschungsgemeinschaft (to W. V., VO657/5-2).

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Rüb, C., Wilkening, A. & Voos, W. Mitochondrial quality control by the Pink1/Parkin system. Cell Tissue Res 367, 111–123 (2017). https://doi.org/10.1007/s00441-016-2485-8

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