Parkin- and PINK1-dependent mitophagy in neurons: Will the real pathway please stand up?

Frontiers in Neurology

Volumn 4 JUL, Issue , 2013, Pages

  Grenier, Karl ^a   McLelland, Gian Luca ^a   Fon, Edward A ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

Autophagy; Mitochondria; Mitophagy; Neurons; Parkin; Parkinson's disease; PINK1

Indexed keywords

AUTOPHAGY PROTEIN 5; LIGASE; MITOCHONDRIAL DNA; MITOCHONDRIAL TRANSCRIPTION FACTOR A; PARKIN; PROTEIN P62; PROTEIN PINK1; UNCLASSIFIED DRUG;

CELL IMMORTALIZATION; DOPAMINERGIC NERVE CELL; ERYTHROCYTE; HUMAN; MITOCHONDRION; MITOPHAGY; NERVE CELL; NERVE CELL DEGENERATION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PARKINSON DISEASE; PARKINSONISM; PROTEIN EXPRESSION; REVIEW; SUBSTANTIA NIGRA;

EID: 84883492814     PISSN: None     EISSN: 16642295     Source Type: Journal    
DOI: 10.3389/fneur.2013.00100     Document Type: Review

References (90)

1. Lill CM, Bertram L. Towards unveiling the genetics of neurodegenerative diseases. Semin Neurol (2011) 31:531-41. doi:10.1055/s-0031-1299791
2. Karbowski M, Neutzner A. Neurodegeneration as a consequence of failed mitochondrial maintenance. Acta Neuropathol (2012) 123:157-71. doi:10.1007/s00401-011-0921-0
3. Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science (1983) 219:979-80. doi:10.1126/science.6823561
4. Schapira AH. Mitochondria in the aetiology and pathogenesis of Parkinson's disease. Lancet Neurol (2008) 7:97-109. doi:10.1016/S1474-4422(07)70327-7
5. Mann VM, Cooper JM, Krige D, Daniel SE, Schapira AH, Marsden CD. Brain, skeletal muscle and platelet homogenate mitochondrial function in Parkinson's disease. Brain (1992) 115(Pt 2):333-42. doi:10.1093/brain/115.2.333
6. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet (2006) 38:515-7. doi:10.1038/ng1769
7. Kraytsberg Y, Kudryavtseva E, McKee AC, Geula C, Kowall NW, Khrapko K. Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet (2006) 38:518-20. doi:10.1038/ng1778
8. Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell (2012) 148:1145-59. doi:10.1016/j.cell.2012.02.035
9. Westermann B. Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol (2010) 11:872-84. doi:10.1038/nrm3013
10. Tatsuta T, Langer T. Quality control of mitochondria: protection against neurodegeneration and ageing. EMBO J (2008) 27:306-14. doi:10.1038/sj.emboj.7601972
11. Ashrafi G, Schwarz TL. The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ (2013) 20:31-42. doi:10.1038/cdd.2012.81
12. Shutt TE, McBride HM. Staying cool in difficult times: mitochondrial dynamics, quality control and the stress response. Biochim Biophys Acta (2013) 1833:417-24. doi:10.1016/j.bbamcr.2012.05.024
13. 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) 22:135-41. doi:10.1016/j.cub.2011.11.057
14. 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:e52830. doi:10.1371/journal.pone.0052830
15. Chan CS, Gertler TS, Surmeier DJ. Calcium homeostasis, selective vulnerability and Parkinson's disease. Trends Neurosci (2009) 32:249-56. doi:10.1016/j.tins.2009.01.006
16. Baxter RV, Ben Othmane K, Rochelle JM, Stajich JE, Hulette C, Dew-Knight S, et al. Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21. Nat Genet (2002) 30:21-2. doi:10.1038/ng796
17. Cuesta A, Pedrola L, Sevilla T, Garcia-Planells J, Chumillas MJ, Mayordomo F, et al. The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease. Nat Genet (2002) 30:22-5. doi:10.1038/ng798
18. Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet (2000) 26:207-10. doi:10.1038/79936
19. Di Bella D, Lazzaro F, Brusco A, Plumari M, Battaglia G, Pastore A, et al. Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28. Nat Genet (2010) 42:313-21. doi:10.1038/ng.544
20. Edener U, Wollner J, Hehr U, Kohl Z, Schilling S, Kreuz F, et al. Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation. Eur J Hum Genet (2010) 18:965-8. doi:10.1038/ejhg.2010.40
21. Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, et al. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet (2000) 25:302-5. doi:10.1038/77060
22. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science (2004) 304:1158-60. doi:10.1126/science.1096284
23. Zuchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, et al. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet (2004) 36:449-51. doi:10.1038/ng1341
24. Schon EA, Przedborski S. Mitochondria: the next (neurode)generation. Neuron (2011) 70:1033-53. doi:10.1016/j
25. 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) 105:14503-8. doi:10.1073/pnas.0803998105
26. 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) 105:1638-43. doi:10.1073/pnas.0709336105
27. Exner N, Treske B, Paquet D, Holmstrom K, Schiesling C, Gispert S, et al. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci (2007) 27:12413-8. doi:10.1523/JNEUROSCI.0719-07.2007
28. Lutz AK, Exner N, Fett ME, Schlehe JS, Kloos K, Lammermann K, et al. Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem (2009) 284:22938-51. doi:10.1074/jbc.M109.035774
29. Mortiboys H, Thomas KJ, Koopman WJ, Klaffke S, Abou-Sleiman P, Olpin S, et al. Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts. Ann Neurol (2008) 64:555-65. doi:10.1002/ana.21492
30. Amo T, Sato S, Saiki S, Wolf AM, Toyomizu M, Gautier CA, et al. Mitochondrial membrane potential decrease caused by loss of PINK1 is not due to proton leak, but to respiratory chain defects. Neurobiol Dis (2011) 41:111-8. doi:10.1016/j.nbd.2010.08.027
31. Gautier CA, Kitada T, Shen J. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci U S A (2008) 105:11364-9. doi:10.1073/pnas.0802076105
32. Gegg ME, Cooper JM, Schapira AH, Taanman JW. Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells. PLoS ONE (2009) 4:e4756. doi:10.1371/journal.pone.0004756
33. Morais VA, Verstreken P, Roethig A, Smet J, Snellinx A, Vanbrabant M, et al. Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function. EMBO Mol Med (2009) 1:99-111. doi:10.1002/emmm.200900006
34. Vilain S, Esposito G, Haddad D, Schaap O, Dobreva MP, Vos M, et al. The yeast complex I equivalent NADH dehydrogenase rescues pink1 mutants. PLoS Genet (2012) 8:e1002456. doi:10.1371/journal.pgen.1002456
35. Gandhi S, Wood-Kaczmar A, Yao Z, Plun-Favreau H, Deas E, Klupsch K, et al. PINK1-associated Parkinson's disease is caused by neuronal vulnerability to calcium-induced cell death. Mol Cell (2009) 33:627-38. doi:10.1016/j.molcel.2009.02.013
36. Heeman B, Van den Haute C, Aelvoet SA, Valsecchi F, Rodenburg RJ, Reumers V, et al. Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance. J Cell Sci (2011) 124:1115-25. doi:10.1242/jcs.078303
37. Marongiu R, Spencer B, Crews L, Adame A, Patrick C, Trejo M, et al. Mutant Pink1 induces mitochondrial dysfunction in a neuronal cell model of Parkinson's disease by disturbing calcium flux. J Neurochem (2009) 108:1561-74. doi:10.1111/j.1471-4159.2009.05932.x
38. Sandebring A, Thomas KJ, Beilina A, van der Brug M, Cleland MM, Ahmad R, et al. Mitochondrial alterations in PINK1 deficient cells are influenced by calcineurin-dependent dephosphorylation of dynamin-related protein 1. PLoS ONE (2009) 4:e5701. doi:10.1371/journal.pone.0005701
39. Greene AW, Grenier K, Aguileta MA, Muise S, Farazifard R, Haque ME, et al. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep (2012) 13:378-85. doi:10.1038/embor.2012.14
40. Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol (2010) 191:933-42. doi:10.1083/jcb.201008084
41. Lazarou M, Jin SM, Kane LA, Youle RJ. Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin. Dev Cell (2012) 22:320-33. doi:10.1016/j.devcel.2011.12.014
42. Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol (2010) 8:e1000298. doi:10.1371/journal.pbio.1000298
43. Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol (2010) 12:119-31. doi:10.1038/ncb2012
44. Lazarou M, Narendra DP, Jin SM, Tekle E, Banerjee S, Youle RJ. PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding. J Cell Biol (2013) 200:163-72. doi:10.1083/jcb.201210111
45. Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol (2010) 189:211-21. doi:10.1083/jcb.200910140
46. Shiba-Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, et al. PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci Rep (2012) 2:1002. doi:10.1038/srep01002
47. 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) 107:378-83. doi:10.1073/pnas.0911187107
48. Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ, Graham RL, et al. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet (2011) 20:1726-37. doi:10.1093/hmg/ddr048
49. 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) 19:4861-70. doi:10.1093/hmg/ddq419
50. Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol (2008) 183:795-803. doi:10.1083/jcb.200809125
51. Poole AC, Thomas RE, Yu S, Vincow ES, Pallanck L. The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway. PLoS ONE (2010) 5:e10054. doi:10.1371/journal.pone.0010054
52. Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol (2010) 191:1367-80. doi:10.1083/jcb.201007013
53. Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, et al. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell (2011) 147:893-906. doi:10.1016/j.cell.2011.10.018
54. Yoshii SR, Kishi C, Ishihara N, Mizushima N. Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane. J Biol Chem (2011) 286:19630-40. doi:10.1074/jbc.M110.209338
55. Ziviani E, Tao RN, Whitworth AJ. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci U S A (2010) 107:5018-23. doi:10.1073/pnas.0913485107
56. Zhang J, Ney PA. Reticulocyte mitophagy: monitoring mitochondrial clearance in a mammalian model. Autophagy (2010) 6:405-8. doi:10.4161/auto.6.3.11245
57. Narendra D, Kane LA, Hauser DN I, Fearnley M, Youle RJ. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy (2010) 6:1090-106. doi:10.4161/auto.6.8.13426
58. Okatsu K, Saisho K, Shimanuki M, Nakada K, Shitara H, Sou YS, et al. p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria. Genes Cells (2010) 15:887-900. doi:10.1111/j.1365-2443.2010.01426.x
59. Suen DF, Narendra DP, Tanaka A, Manfredi G, Youle RJ. Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells. Proc Natl Acad Sci U S A (2010) 107:11835-40. doi:10.1073/pnas.0914569107
60. Ney PA. Normal and disordered reticulocyte maturation. Curr Opin Hematol (2011) 18:152-7. doi:10.1097/MOH.0b013e328345213e
61. Heynen MJ, Verwilghen RL. A quantitative ultrastructural study of normal rat erythroblasts and reticulocytes. Cell Tissue Res (1982) 224:397-408. doi:10.1007/BF00216882
62. Fader CM, Colombo MI. Multivesicular bodies and autophagy in erythrocyte maturation. Autophagy (2006) 2:122-5.
63. Ding WX, Ni HM, Li M, Liao Y, Chen X, Stolz DB, et al. Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. J Biol Chem (2010) 285:27879-90. doi:10.1074/jbc.M110.119537
64. Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A, et al. Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep (2010) 11:45-51. doi:10.1038/embor.2009.256
65. Zhang J, Randall MS, Loyd MR, Dorsey FC, Kundu M, Cleveland JL, et al. Mitochondrial clearance is regulated by Atg7-dependent and -independent mechanisms during reticulocyte maturation. Blood (2009) 114:157-64. doi:10.1182/blood-2008-04-151639
66. Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M, et al. Essential role for Nix in autophagic maturation of erythroid cells. Nature (2008) 454:232-5. doi:10.1038/nature07006
67. Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci U S A (2007) 104:19500-5. doi:10.1073/pnas.0708818104
68. Mortensen M, Ferguson DJ, Edelmann M, Kessler B, Morten KJ, Komatsu M, et al. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci USA (2010) 107:832-7. doi:10.1073/pnas.0913170107
69. Dumollard R, Duchen M, Carroll J. The role of mitochondrial function in the oocyte and embryo. Curr Top Dev Biol (2007) 77:21-49. doi:10.1016/S0070-2153(06)77002-8
70. Al Rawi S, Louvet-Vallee S, Djeddi A, Sachse M, Culetto E, Hajjar C, et al. Postfertilization autophagy of sperm organelles prevents paternal mitochondrial DNA transmission. Science (2011) 334:1144-7. doi:10.1126/science.1211878
71. Cummins JM. Fertilization and elimination of the paternal mitochondrial genome. Hum Reprod (2000) 15(Suppl 2):92-101. doi:10.1093/humrep/15.suppl_2.92
72. Sato M, Sato K. Degradation of paternal mitochondria by fertilization-triggered autophagy in C. elegans embryos. Science (2011) 334:1141-4. doi:10.1126/science.1210333
73. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, et al. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature (2006) 441:1162-6. doi:10.1038/nature04779
74. Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci U S A (2003) 100:4078-83. doi:10.1073/pnas.0737556100
75. Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, et al. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature (2006) 441:1157-61. doi:10.1038/nature04788
76. 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) 22:545-52. doi:10.1016/j.cub.2012.02.005
77. Joselin AP, Hewitt SJ, Callaghan SM, Kim RH, Chung YH, Mak TW, et al. ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons. Hum Mol Genet (2012) 21:4888-903. doi:10.1093/hmg/dds325
78. 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) 31:5970-6. doi:10.1523/JNEUROSCI.4441-10.2011
79. 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) 20:927-40. doi:10.1093/hmg/ddq531
80. Rakovic A, Shurkewitsch K, Seibler P, Grunewald A, Zanon A, Hagenah J, et al. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons. J Biol Chem (2013) 288:2223-37. doi:10.1074/jbc.M112.391680
81. Almeida A, Almeida J, Bolanos JP, Moncada S. Different responses of astrocytes and neurons to nitric oxide: the role of glycolytically generated ATP in astrocyte protection. Proc Natl Acad Sci U S A (2001) 98:15294-9. doi:10.1073/pnas.261560998
82. Almeida A, Moncada S, Bolanos JP. Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway. Nat Cell Biol (2004) 6:45-51. doi:10.1038/ncb1080
83. Bolanos JP, Almeida A, Moncada S. Glycolysis: a bioenergetic or a survival pathway?. Trends Biochem Sci (2010) 35:145-9. doi:10.1016/j.tibs.2009.10.006
84. Herrero-Mendez A, Almeida A, Fernandez E, Maestre C, Moncada S, Bolanos JP. The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1. Nat Cell Biol (2009) 11:747-52. doi:10.1038/ncb1881
85. Ekstrand MI, Terzioglu M, Galter D, Zhu S, Hofstetter C, Lindqvist E, et al. Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons. Proc Natl Acad Sci U S A (2007) 104:1325-30. doi:10.1073/pnas.0605208103
86. Sterky FH, Lee S, Wibom R, Olson L, Larsson NG. Impaired mitochondrial transport and Parkin-independent degeneration of respiratory chain-deficient dopamine neurons in vivo. Proc Natl Acad Sci USA (2011) 108:12937-42. doi:10.1073/pnas.1103295108
87. 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) 110:6400-5. doi:10.1073/pnas.1221132110
88. Lee JY, Nagano Y, Taylor JP, Lim KL, Yao TP. Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. J Cell Biol (2010) 189:671-9. doi:10.1083/jcb.201001039
89. Sun Y, Vashisht AA, Tchieu J, Wohlschlegel JA, Dreier L. Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy. J Biol Chem (2012) 287:40652-60. doi:10.1074/jbc.M112.419721
90. Van Humbeeck C, Cornelissen T, Hofkens H, Mandemakers W, Gevaert K, De Strooper B, et al. Parkin interacts with Ambra1 to induce mitophagy. J Neurosci (2011) 31:10249-61. doi:10.1523/JNEUROSCI.1917-11.2011