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Twenty years since the discovery of the parkin gene

  • High Impact Review in Neuroscience, Neurology or Psychiatry - Review Article
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Abstract

Nearly 20 years have passed since we identified the causative gene for a familial Parkinson’s disease, parkin (now known as PARK2), in 1998. PARK2 is the most common gene responsible for young-onset Parkinson’s disease. It codes for the protein Parkin RBR E3 ubiquitin-protein ligase (PARK2), which directly links to the ubiquitin-proteasome as a ubiquitin ligase. PARK2 is involved in mitophagy, which is a type of autophagy, in collaboration with PTEN-induced putative kinase 1 (PINK1). The PINK1 gene (previously known as PARK6) is also a causative gene for young-onset Parkinson’s disease. Both gene products may be involved in regulating quality control within the mitochondria. The discovery of PARK2 as a cause of young-onset Parkinson’s disease has had a major impact on other neurodegenerative diseases. The involvement of protein degradation systems has been implicated as a common mechanism for neurodegenerative diseases in which inclusion body formation is observed. The discovery of the involvement of PARK2 in Parkinson’s disease focused attention on the involvement of protein degradation systems in neurodegenerative diseases. In this review, we focus on the history of the discovery of PARK2, the clinical phenotypes of patients with PARK2 mutations, and its functional roles.

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Cite at Tanaka et al. (2004)

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References

  • Abbas N, Lucking CB, Ricard S, Durr A, Bonifati V, De Michele G, Bouley S, Vaughan JR, Gasser T, Marconi R, Broussolle E, Brefel-Courbon C, Harhangi BS, Oostra BA, Fabrizio E, Bohme GA, Pradier L, Wood NW, Filla A, Meco G, Denefle P, Agid Y, Brice A (1999) A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson’s Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson’s Disease. Hum Mol Genet 8(4):567–574

    Article  CAS  PubMed  Google Scholar 

  • Abbruzzese G, Pigullo S, Schenone A, Bellone E, Marchese R, Di Maria E, Benedetti L, Ciotti P, Nobbio L, Bonifati V, Ajmar F, Mandich P (2004) Does parkin play a role in the peripheral nervous system? A family report. Mov Disord 19(8):978–981. doi:10.1002/mds.20113

    Article  PubMed  Google Scholar 

  • Adel S, Djarmati A, Kabakci K, Pichler I, Eskelson C, Lohnau T, Kock N, Hagenah J, Hedrich K, Schwinger E, Kramer PL, Pramstaller PP, Klein C (2006) Co-occurrence of restless legs syndrome and Parkin mutations in two families. Mov Disord 21(2):258–263. doi:10.1002/mds.20690

    Article  PubMed  Google Scholar 

  • Ageta-Ishihara N, Yamakado H, Morita T, Hattori S, Takao K, Miyakawa T, Takahashi R, Kinoshita M (2013) Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson’s disease, causes behavioral alterations but not neurodegeneration in mice. Mol Brain 6:35. doi:10.1186/1756-6606-6-35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aguirre JD, Dunkerley KM, Mercier P, Shaw GS (2016) Structure of phosphorylated UBL domain and insights into PINK1-orchestrated parkin activation. Proc Natl Acad Sci USA. doi:10.1073/pnas.1613040114

    Google Scholar 

  • Alvarez V, Guisasola LM, Moreira VG, Lahoz CH, Coto E (2001) Early-onset Parkinson’s disease associated with a new parkin mutation in a Spanish family. Neurosci Lett 313(1–2):108–110

    Article  CAS  PubMed  Google Scholar 

  • Arano T, Imai Y (2015) Mitophagy regulated by the PINK1-Parkin pathway, Chapter 6. In: Cell death-Autophagy, Apotosis and Necrosis. InTech, Chapters published

  • Asakawa S, Abe I, Kudoh Y, Kishi N, Wang Y, Kubota R, Kudoh J, Kawasaki K, Minoshima S, Shimizu N (1997) Human BAC library: construction and rapid screening. Gene 191(1):69–79

    Article  CAS  PubMed  Google Scholar 

  • Autere JM, Hiltunen MJ, Mannermaa AJ, Jakala PA, Hartikainen PH, Majamaa K, Alafuzoff I, Soininen HS (2002) Molecular genetic analysis of the alpha-synuclein and the parkin gene in Parkinson’s disease in Finland. Eur J Neurol 9(5):479–483

    Article  CAS  PubMed  Google Scholar 

  • Beck Y, Oren R, Amit B, Levanon A, Gorecki M, Hartman JR (1987) Human Mn superoxide dismutase cDNA sequence. Nucleic Acids Res 15(21):9076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertoli-Avella AM, Giroud-Benitez JL, Akyol A, Barbosa E, Schaap O, van der Linde HC, Martignoni E, Lopiano L, Lamberti P, Fincati E, Antonini A, Stocchi F, Montagna P, Squitieri F, Marini P, Abbruzzese G, Fabbrini G, Marconi R, Dalla Libera A, Trianni G, Guidi M, De Gaetano A, Boff Maegawa G, De Leo A, Gallai V, de Rosa G, Vanacore N, Meco G, van Duijn CM, Oostra BA, Heutink P, Bonifati V, Italian Parkinson Genetics N (2005) Novel parkin mutations detected in patients with early-onset Parkinson’s disease. Mov Disord 20(4):424–431. doi:10.1002/mds.20343

    Article  PubMed  Google Scholar 

  • Casarejos MJ, Menendez J, Solano RM, Rodriguez-Navarro JA, Garcia de Yebenes J, Mena MA (2006) Susceptibility to rotenone is increased in neurons from parkin null mice and is reduced by minocycline. J Neurochem 97(4):934–946. doi:10.1111/j.1471-4159.2006.03777.x

    Article  CAS  PubMed  Google Scholar 

  • Choi P, Snyder H, Petrucelli L, Theisler C, Chong M, Zhang Y, Lim K, Chung KK, Kehoe K, D’Adamio L, Lee JM, Cochran E, Bowser R, Dawson TM, Wolozin B (2003) SEPT5_v2 is a parkin-binding protein. Brain Res Mol Brain Res 117(2):179–189

    Article  CAS  PubMed  Google Scholar 

  • Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM (2001) Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med 7(10):1144–1150. doi:10.1038/nm1001-1144

    Article  CAS  PubMed  Google Scholar 

  • Clarimon J, Johnson J, Dogu O, Horta W, Khan N, Lees AJ, Hardy J, Singleton A (2005) Defining the ends of Parkin exon 4 deletions in two different families with Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet 133B(1):120–123. doi:10.1002/ajmg.b.30119

    Article  PubMed  Google Scholar 

  • Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M (2006a) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441(7097):1162–1166. doi:10.1038/nature04779

    Article  CAS  PubMed  Google Scholar 

  • Clark LN, Afridi S, Karlins E, Wang Y, Mejia-Santana H, Harris J, Louis ED, Cote LJ, Andrews H, Fahn S, Waters C, Ford B, Frucht S, Ottman R, Marder K (2006b) Case-control study of the parkin gene in early-onset Parkinson disease. Arch Neurol 63(4):548–552. doi:10.1001/archneur.63.4.548

    Article  PubMed  Google Scholar 

  • Clark LN, Haamer E, Mejia-Santana H, Harris J, Lesage S, Durr A, Bs SJ, Hedrich K, Louis ED, Cote LJ, Andrews H, Fahn S, Waters C, Ford B, Frucht S, Scott W, Klein C, Brice A, Roomere H, Ottman R, Marder K (2007) Construction and validation of a Parkinson’s disease mutation genotyping array for the Parkin gene. Mov Disord 22(7):932–937. doi:10.1002/mds.21419

    Article  PubMed  Google Scholar 

  • Corti O, Hampe C, Koutnikova H, Darios F, Jacquier S, Prigent A, Robinson JC, Pradier L, Ruberg M, Mirande M, Hirsch E, Rooney T, Fournier A, Brice A (2003) The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration. Hum Mol Genet 12(12):1427–1437

    Article  CAS  PubMed  Google Scholar 

  • de Duve D (1969) The peroxisome: a new cytoplasmic organelle. Proc R Soc Lond B Biol Sci 173(1030):71–83

    Article  Google Scholar 

  • Deng H, Le WD, Hunter CB, Ondo WG, Guo Y, Xie WJ, Jankovic J (2006) Heterogeneous phenotype in a family with compound heterozygous parkin gene mutations. Arch Neurol 63(2):273–277. doi:10.1001/archneur.63.2.273

    Article  PubMed  Google Scholar 

  • Dogu O, Johnson J, Hernandez D, Hanson M, Hardy J, Apaydin H, Ozekmekci S, Sevim S, Gwinn-Hardy K, Singleton A (2004) A consanguineous Turkish family with early-onset Parkinson’s disease and an exon 4 parkin deletion. Mov Disord 19(7):812–816. doi:10.1002/mds.20028

    Article  PubMed  Google Scholar 

  • Dusonchet J, Bensadoun JC, Schneider BL, Aebischer P (2009) Targeted overexpression of the parkin substrate Pael-R in the nigrostriatal system of adult rats to model Parkinson’s disease. Neurobiol Dis 35(1):32–41. doi:10.1016/j.nbd.2009.03.013

    Article  CAS  PubMed  Google Scholar 

  • Ekholm-Reed S, Goldberg MS, Schlossmacher MG, Reed SI (2013) Parkin-dependent degradation of the F-box protein Fbw7beta promotes neuronal survival in response to oxidative stress by stabilizing Mcl-1. Mol Cell Biol 33(18):3627–3643. doi:10.1128/MCB.00535-13

    Article  CAS  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(45):12413–12418. doi:10.1523/JNEUROSCI.0719-07.2007

    Article  CAS  PubMed  Google Scholar 

  • Farrer M, Chan P, Chen R, Tan L, Lincoln S, Hernandez D, Forno L, Gwinn-Hardy K, Petrucelli L, Hussey J, Singleton A, Tanner C, Hardy J, Langston JW (2001) Lewy bodies and parkinsonism in families with parkin mutations. Ann Neurol 50(3):293–300

    Article  CAS  PubMed  Google Scholar 

  • Foroud T, Uniacke SK, Liu L, Pankratz N, Rudolph A, Halter C, Shults C, Marder K, Conneally PM, Nichols WC, Parkinson Study G (2003) Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology 60(5):796-801

  • Gao F, Chen D, Si J, Hu Q, Qin Z, Fang M, Wang G (2015) The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway. Hum Mol Genet 24(9):2528–2538. doi:10.1093/hmg/ddv017

    Article  CAS  PubMed  Google Scholar 

  • Gautier CA, Erpapazoglou Z, Mouton-Liger F, Muriel MP, Cormier F, Bigou S, Duffaure S, Girard M, Foret B, Iannielli A, Broccoli V, Dalle C, Bohl D, Michel PP, Corvol JC, Brice A, Corti O (2016) The endoplasmic reticulum–mitochondria interface is perturbed in PARK2 knockout mice and patients with PARK2 mutations. Hum Mol Genet 25(14):2972–2984. doi:10.1093/hmg/ddw148

    CAS  PubMed  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(24):4861–4870. doi:10.1093/hmg/ddq419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glauser L, Sonnay S, Stafa K, Moore DJ (2011) Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1. J Neurochem 118(4):636–645. doi:10.1111/j.1471-4159.2011.07318.x

    Article  CAS  PubMed  Google Scholar 

  • Goldberg MS, Fleming SM, Palacino JJ, Cepeda C, Lam HA, Bhatnagar A, Meloni EG, Wu N, Ackerson LC, Klapstein GJ, Gajendiran M, Roth BL, Chesselet MF, Maidment NT, Levine MS, Shen J (2003) Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem 278(44):43628–43635. doi:10.1074/jbc.M308947200

    Article  CAS  PubMed  Google Scholar 

  • Gouider-Khouja N, Larnaout A, Amouri R, Sfar S, Belal S, Ben Hamida C, Ben Hamida M, Hattori N, Mizuno Y, Hentati F (2003) Autosomal recessive parkinsonism linked to parkin gene in a Tunisian family. Clinical, genetic and pathological study. Parkinsonism Relat Disord 9(5):247–251

    Article  PubMed  Google Scholar 

  • Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ (2003) Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci USA 100(7):4078–4083. doi:10.1073/pnas.0737556100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hattori N, Kitada T, Matsumine H, Asakawa S, Yamamura Y, Yoshino H, Kobayashi T, Yokochi M, Wang M, Yoritaka A, Kondo T, Kuzuhara S, Nakamura S, Shimizu N, Mizuno Y (1998a) Molecular genetic analysis of a novel Parkin gene in Japanese families with autosomal recessive juvenile parkinsonism: evidence for variable homozygous deletions in the Parkin gene in affected individuals. Ann Neurol 44(6):935–941. doi:10.1002/ana.410440612

    Article  CAS  PubMed  Google Scholar 

  • Hattori N, Matsumine H, Asakawa S, Kitada T, Yoshino H, Elibol B, Brookes AJ, Yamamura Y, Kobayashi T, Wang M, Yoritaka A, Minoshima S, Shimizu N, Mizuno Y (1998b) Point mutations (Thr240Arg and Gln311Stop) [correction of Thr240Arg and Ala311Stop] in the Parkin gene. Biochem Biophys Res Commun 249(3):754–758

    Article  CAS  PubMed  Google Scholar 

  • Hedrich K, Marder K, Harris J, Kann M, Lynch T, Meija-Santana H, Pramstaller PP, Schwinger E, Bressman SB, Fahn S, Klein C (2002) Evaluation of 50 probands with early-onset Parkinson’s disease for Parkin mutations. Neurology 58(8):1239–1246

    Article  CAS  PubMed  Google Scholar 

  • Hedrich K, Pramstaller PP, Stubke K, Hiller A, Kabakci K, Purmann S, Kasten M, Scaglione C, Schwinger E, Volkmann J, Kostic V, Vieregge P, Martinelli P, Abbruzzese G, Klein C, Zuhlke C (2005) Premutations in the FMR1 gene as a modifying factor in Parkin-associated Parkinson’s disease? Mov Disord 20(8):1060–1062. doi:10.1002/mds.20512

    Article  PubMed  Google Scholar 

  • Hertz JM, Ostergaard K, Juncker I, Pedersen S, Romstad A, Moller LB, Guttler F, Dupont E (2006) Low frequency of parkin, tyrosine hydroxylase, and GTP cyclohydrolase I gene mutations in a Danish population of early-onset Parkinson’s disease. Eur J Neurol 13(4):385–390. doi:10.1111/j.1468-1331.2006.01249.x

    Article  CAS  PubMed  Google Scholar 

  • Hilker R, Klein C, Hedrich K, Ozelius LJ, Vieregge P, Herholz K, Pramstaller PP, Heiss WD (2002) The striatal dopaminergic deficit is dependent on the number of mutant alleles in a family with mutations in the parkin gene: evidence for enzymatic parkin function in humans. Neurosci Lett 323(1):50–54

    Article  CAS  PubMed  Google Scholar 

  • Hoenicka J, Vidal L, Morales B, Ampuero I, Jimenez-Jimenez FJ, Berciano J, del Ser T, Jimenez A, Ruiz PG, de Yebenes JG (2002) Molecular findings in familial Parkinson disease in Spain. Arch Neurol 59(6):966–970

    Article  PubMed  Google Scholar 

  • Hristova VA, Beasley SA, Rylett RJ, Shaw GS (2009) Identification of a novel Zn2+-binding domain in the autosomal recessive juvenile Parkinson-related E3 ligase parkin. J Biol Chem 284(22):14978–14986. doi:10.1074/jbc.M808700200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huynh DP, Scoles DR, Nguyen D, Pulst SM (2003) The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI. Hum Mol Genet 12(20):2587–2597. doi:10.1093/hmg/ddg269

    Article  CAS  PubMed  Google Scholar 

  • Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R (2001) An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105(7):891–902

    Article  CAS  PubMed  Google Scholar 

  • Imaizumi Y, Okada Y, Akamatsu W, Koike M, Kuzumaki N, Hayakawa H, Nihira T, Kobayashi T, Ohyama M, Sato S, Takanashi M, Funayama M, Hirayama A, Soga T, Hishiki T, Suematsu M, Yagi T, Ito D, Kosakai A, Hayashi K, Shouji M, Nakanishi A, Suzuki N, Mizuno Y, Mizushima N, Amagai M, Uchiyama Y, Mochizuki H, Hattori N, Okano H (2012) Mitochondrial dysfunction associated with increased oxidative stress and alpha-synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue. Mol Brain 5:35. doi:10.1186/1756-6606-5-35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itier JM, Ibanez P, Mena MA, Abbas N, Cohen-Salmon C, Bohme GA, Laville M, Pratt J, Corti O, Pradier L, Ret G, Joubert C, Periquet M, Araujo F, Negroni J, Casarejos MJ, Canals S, Solano R, Serrano A, Gallego E, Sanchez M, Denefle P, Benavides J, Tremp G, Rooney TA, Brice A, Garcia de Yebenes J (2003) Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum Mol Genet 12(18):2277–2291. doi:10.1093/hmg/ddg239

    Article  CAS  PubMed  Google Scholar 

  • Kagi G, Klein C, Wood NW, Schneider SA, Pramstaller PP, Tadic V, Quinn NP, van de Warrenburg BP, Bhatia KP (2010) Nonmotor symptoms in Parkin gene-related parkinsonism. Mov Disord 25(9):1279–1284. doi:10.1002/mds.22897

    Article  PubMed  Google Scholar 

  • Kalia SK, Lee S, Smith PD, Liu L, Crocker SJ, Thorarinsdottir TE, Glover JR, Fon EA, Park DS, Lozano AM (2004) BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. Neuron 44(6):931–945. doi:10.1016/j.neuron.2004.11.026

    Article  CAS  PubMed  Google Scholar 

  • Kasai S, Torii S, Kakita A, Sogawa K (2015) Inhibitory PAS domain protein is a substrate of PINK1 and Parkin and mediates cell death in a Parkinson’s disease model. Cell Death Dis 6:e1886. doi:10.1038/cddis.2015.243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kay DM, Moran D, Moses L, Poorkaj P, Zabetian CP, Nutt J, Factor SA, Yu CE, Montimurro JS, Keefe RG, Schellenberg GD, Payami H (2007) Heterozygous parkin point mutations are as common in control subjects as in Parkinson’s patients. Ann Neurol 61(1):47–54. doi:10.1002/ana.21039

    Article  CAS  PubMed  Google Scholar 

  • Kazlauskaite A, Kelly V, Johnson C, Baillie C, Hastie CJ, Peggie M, Macartney T, Woodroof HI, Alessi DR, Pedrioli PG, Muqit MM (2014) Phosphorylation of Parkin at Serine65 is essential for activation: elaboration of a Miro1 substrate-based assay of Parkin E3 ligase activity. Open Biol 4:130213. doi:10.1098/rsob.130213

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Khan NL, Brooks DJ, Pavese N, Sweeney MG, Wood NW, Lees AJ, Piccini P (2002) Progression of nigrostriatal dysfunction in a parkin kindred: an [18F]dopa PET and clinical study. Brain 125(Pt 10):2248–2256

    Article  PubMed  Google Scholar 

  • Khan NL, Graham E, Critchley P, Schrag AE, Wood NW, Lees AJ, Bhatia KP, Quinn N (2003) Parkin disease: a phenotypic study of a large case series. Brain 126(Pt 6):1279–1292

    Article  PubMed  Google Scholar 

  • Khan NL, Katzenschlager R, Watt H, Bhatia KP, Wood NW, Quinn N, Lees AJ (2004) Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease. Neurology 62(7):1224–1226

    Article  CAS  PubMed  Google Scholar 

  • Khan NL, Scherfler C, Graham E, Bhatia KP, Quinn N, Lees AJ, Brooks DJ, Wood NW, Piccini P (2005) Dopaminergic dysfunction in unrelated, asymptomatic carriers of a single parkin mutation. Neurology 64(1):134–136. doi:10.1212/01.WNL.0000148725.48740.6D

    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(6676):605–608. doi:10.1038/33416

    Article  CAS  PubMed  Google Scholar 

  • Klein RL, Dayton RD, Henderson KM, Petrucelli L (2006) Parkin is protective for substantia nigra dopamine neurons in a tau gene transfer neurodegeneration model. Neurosci Lett 401(1–2):130–135. doi:10.1016/j.neulet.2006.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, Ahn HJ, Ait-Mohamed O, Ait-Si-Ali S, Akematsu T, Akira S, Al-Younes HM, Al-Zeer MA, Albert ML, Albin RL, Alegre-Abarrategui J, Aleo MF, Alirezaei M, Almasan A, Almonte-Becerril M, Amano A, Amaravadi R, Amarnath S, Amer AO, Andrieu-Abadie N, Anantharam V, Ann DK, Anoopkumar-Dukie S, Aoki H, Apostolova N, Arancia G, Aris JP, Asanuma K, Asare NY, Ashida H, Askanas V, Askew DS, Auberger P, Baba M, Backues SK, Baehrecke EH, Bahr BA, Bai XY, Bailly Y, Baiocchi R, Baldini G, Balduini W, Ballabio A, Bamber BA, Bampton ET, Banhegyi G, Bartholomew CR, Bassham DC, Bast RC Jr, Batoko H, Bay BH, Beau I, Bechet DM, Begley TJ, Behl C, Behrends C, Bekri S, Bellaire B, Bendall LJ, Benetti L, Berliocchi L, Bernardi H, Bernassola F, Besteiro S, Bhatia-Kissova I, Bi X, Biard-Piechaczyk M, Blum JS, Boise LH, Bonaldo P, Boone DL, Bornhauser BC, Bortoluci KR, Bossis I, Bost F, Bourquin JP, Boya P, Boyer-Guittaut M, Bozhkov PV, Brady NR, Brancolini C, Brech A, Brenman JE, Brennand A, Bresnick EH, Brest P, Bridges D, Bristol ML, Brookes PS, Brown EJ, Brumell JH, Brunetti-Pierri N, Brunk UT, Bulman DE, Bultman SJ, Bultynck G, Burbulla LF, Bursch W, Butchar JP, Buzgariu W, Bydlowski SP, Cadwell K, Cahova M, Cai D, Cai J, Cai Q, Calabretta B, Calvo-Garrido J, Camougrand N, Campanella M, Campos-Salinas J, Candi E, Cao L, Caplan AB, Carding SR, Cardoso SM, Carew JS, Carlin CR, Carmignac V, Carneiro LA, Carra S, Caruso RA, Casari G, Casas C, Castino R, Cebollero E, Cecconi F, Celli J, Chaachouay H, Chae HJ, Chai CY, Chan DC, Chan EY, Chang RC, Che CM, Chen CC, Chen GC, Chen GQ, Chen M, Chen Q, Chen SS, Chen W, Chen X, Chen X, Chen X, Chen YG, Chen Y, Chen Y, Chen YJ, Chen Z, Cheng A, Cheng CH, Cheng Y, Cheong H, Cheong JH, Cherry S, Chess-Williams R, Cheung ZH, Chevet E, Chiang HL, Chiarelli R, Chiba T, Chin LS, Chiou SH, Chisari FV, Cho CH, Cho DH, Choi AM, Choi D, Choi KS, Choi ME, Chouaib S, Choubey D, Choubey V, Chu CT, Chuang TH, Chueh SH, Chun T, Chwae YJ, Chye ML, Ciarcia R, Ciriolo MR, Clague MJ, Clark RS, Clarke PG, Clarke R, Codogno P, Coller HA, Colombo MI, Comincini S, Condello M, Condorelli F, Cookson MR, Coombs GH, Coppens I, Corbalan R, Cossart P, Costelli P, Costes S, Coto-Montes A, Couve E, Coxon FP, Cregg JM, Crespo JL, Cronje MJ, Cuervo AM, Cullen JJ, Czaja MJ, D’Amelio M, Darfeuille-Michaud A, Davids LM, Davies FE, De Felici M, de Groot JF, de Haan CA, De Martino L, De Milito A, De Tata V, Debnath J, Degterev A, Dehay B, Delbridge LM, Demarchi F, Deng YZ, Dengjel J, Dent P, Denton D, Deretic V, Desai SD, Devenish RJ, Di Gioacchino M, Di Paolo G, Di Pietro C, Diaz-Araya G, Diaz-Laviada I, Diaz-Meco MT, Diaz-Nido J, Dikic I, Dinesh-Kumar SP, Ding WX, Distelhorst CW, Diwan A, Djavaheri-Mergny M, Dokudovskaya S, Dong Z, Dorsey FC, Dosenko V, Dowling JJ, Doxsey S, Dreux M, Drew ME, Duan Q, Duchosal MA, Duff K, Dugail I, Durbeej M, Duszenko M, Edelstein CL, Edinger AL, Egea G, Eichinger L, Eissa NT, Ekmekcioglu S, El-Deiry WS, Elazar Z, Elgendy M, Ellerby LM, Eng KE, Engelbrecht AM, Engelender S, Erenpreisa J, Escalante R, Esclatine A, Eskelinen EL, Espert L, Espina V, Fan H, Fan J, Fan QW, Fan Z, Fang S, Fang Y, Fanto M, Fanzani A, Farkas T, Farre JC, Faure M, Fechheimer M, Feng CG, Feng J, Feng Q, Feng Y, Fesus L, Feuer R, Figueiredo-Pereira ME, Fimia GM, Fingar DC, Finkbeiner S, Finkel T, Finley KD, Fiorito F, Fisher EA, Fisher PB, Flajolet M, Florez-McClure ML, Florio S, Fon EA, Fornai F, Fortunato F, Fotedar R, Fowler DH, Fox HS, Franco R, Frankel LB, Fransen M, Fuentes JM, Fueyo J, Fujii J, Fujisaki K, Fujita E, Fukuda M, Furukawa RH, Gaestel M, Gailly P, Gajewska M, Galliot B, Galy V, Ganesh S, Ganetzky B, Ganley IG, Gao FB, Gao GF, Gao J, Garcia L, Garcia-Manero G, Garcia-Marcos M, Garmyn M, Gartel AL, Gatti E, Gautel M, Gawriluk TR, Gegg ME, Geng J, Germain M, Gestwicki JE, Gewirtz DA, Ghavami S, Ghosh P, Giammarioli AM, Giatromanolaki AN, Gibson SB, Gilkerson RW, Ginger ML, Ginsberg HN, Golab J, Goligorsky MS, Golstein P, Gomez-Manzano C, Goncu E, Gongora C, Gonzalez CD, Gonzalez R, Gonzalez-Estevez C, Gonzalez-Polo RA, Gonzalez-Rey E, Gorbunov NV, Gorski S, Goruppi S, Gottlieb RA, Gozuacik D, Granato GE, Grant GD, Green KN, Gregorc A, Gros F, Grose C, Grunt TW, Gual P, Guan JL, Guan KL, Guichard SM, Gukovskaya AS, Gukovsky I, Gunst J, Gustafsson AB, Halayko AJ, Hale AN, Halonen SK, Hamasaki M, Han F, Han T, Hancock MK, Hansen M, Harada H, Harada M, Hardt SE, Harper JW, Harris AL, Harris J, Harris SD, Hashimoto M, Haspel JA, Hayashi S, Hazelhurst LA, He C, He YW, Hebert MJ, Heidenreich KA, Helfrich MH, Helgason GV, Henske EP, Herman B, Herman PK, Hetz C, Hilfiker S, Hill JA, Hocking LJ, Hofman P, Hofmann TG, Hohfeld J, Holyoake TL, Hong MH, Hood DA, Hotamisligil GS, Houwerzijl EJ, Hoyer-Hansen M, Hu B, Hu CA, Hu HM, Hua Y, Huang C, Huang J, Huang S, Huang WP, Huber TB, Huh WK, Hung TH, Hupp TR, Hur GM, Hurley JB, Hussain SN, Hussey PJ, Hwang JJ, Hwang S, Ichihara A, Ilkhanizadeh S, Inoki K, Into T, Iovane V, Iovanna JL, Ip NY, Isaka Y, Ishida H, Isidoro C, Isobe K, Iwasaki A, Izquierdo M, Izumi Y, Jaakkola PM, Jaattela M, Jackson GR, Jackson WT, Janji B, Jendrach M, Jeon JH, Jeung EB, Jiang H, Jiang H, Jiang JX, Jiang M, Jiang Q, Jiang X, Jiang X, Jimenez A, Jin M, Jin S, Joe CO, Johansen T, Johnson DE, Johnson GV, Jones NL, Joseph B, Joseph SK, Joubert AM, Juhasz G, Juillerat-Jeanneret L, Jung CH, Jung YK, Kaarniranta K, Kaasik A, Kabuta T, Kadowaki M, Kagedal K, Kamada Y, Kaminskyy VO, Kampinga HH, Kanamori H, Kang C, Kang KB, Kang KI, Kang R, Kang YA, Kanki T, Kanneganti TD, Kanno H, Kanthasamy AG, Kanthasamy A, Karantza V, Kaushal GP, Kaushik S, Kawazoe Y, Ke PY, Kehrl JH, Kelekar A, Kerkhoff C, Kessel DH, Khalil H, Kiel JA, Kiger AA, Kihara A, Kim DR, Kim DH, Kim DH, Kim EK, Kim HR, Kim JS, Kim JH, Kim JC, Kim JK, Kim PK, Kim SW, Kim YS, Kim Y, Kimchi A, Kimmelman AC, King JS, Kinsella TJ, Kirkin V, Kirshenbaum LA, Kitamoto K, Kitazato K, Klein L, Klimecki WT, Klucken J, Knecht E, Ko BC, Koch JC, Koga H, Koh JY, Koh YH, Koike M, Komatsu M, Kominami E, Kong HJ, Kong WJ, Korolchuk VI, Kotake Y, Koukourakis MI, Kouri Flores JB, Kovacs AL, Kraft C, Krainc D, Kramer H, Kretz-Remy C, Krichevsky AM, Kroemer G, Kruger R, Krut O, Ktistakis NT, Kuan CY, Kucharczyk R, Kumar A, Kumar R, Kumar S, Kundu M, Kung HJ, Kurz T, Kwon HJ, La Spada AR, Lafont F, Lamark T, Landry J, Lane JD, Lapaquette P, Laporte JF, Laszlo L, Lavandero S, Lavoie JN, Layfield R, Lazo PA, Le W, Le Cam L, Ledbetter DJ, Lee AJ, Lee BW, Lee GM, Lee J, Lee JH, Lee M, Lee MS, Lee SH, Leeuwenburgh C, Legembre P, Legouis R, Lehmann M, Lei HY, Lei QY, Leib DA, Leiro J, Lemasters JJ, Lemoine A, Lesniak MS, Lev D, Levenson VV, Levine B, Levy E, Li F, Li JL, Li L, Li S, Li W, Li XJ, Li YB, Li YP, Liang C, Liang Q, Liao YF, Liberski PP, Lieberman A, Lim HJ, Lim KL, Lim K, Lin CF, Lin FC, Lin J, Lin JD, Lin K, Lin WW, Lin WC, Lin YL, Linden R, Lingor P, Lippincott-Schwartz J, Lisanti MP, Liton PB, Liu B, Liu CF, Liu K, Liu L, Liu QA, Liu W, Liu YC, Liu Y, Lockshin RA, Lok CN, Lonial S, Loos B, Lopez-Berestein G, Lopez-Otin C, Lossi L, Lotze MT, Low P, Lu B, Lu B, Lu B, Lu Z, Luciano F, Lukacs NW, Lund AH, Lynch-Day MA, Ma Y, Macian F, MacKeigan JP, Macleod KF, Madeo F, Maiuri L, Maiuri MC, Malagoli D, Malicdan MC, Malorni W, Man N, Mandelkow EM, Manon S, Manov I, Mao K, Mao X, Mao Z, Marambaud P, Marazziti D, Marcel YL, Marchbank K, Marchetti P, Marciniak SJ, Marcondes M, Mardi M, Marfe G, Marino G, Markaki M, Marten MR, Martin SJ, Martinand-Mari C, Martinet W, Martinez-Vicente M, Masini M, Matarrese P, Matsuo S, Matteoni R, Mayer A, Mazure NM, McConkey DJ, McConnell MJ, McDermott C, McDonald C, McInerney GM, McKenna SL, McLaughlin B, McLean PJ, McMaster CR, McQuibban GA, Meijer AJ, Meisler MH, Melendez A, Melia TJ, Melino G, Mena MA, Menendez JA, Menna-Barreto RF, Menon MB, Menzies FM, Mercer CA, Merighi A, Merry DE, Meschini S, Meyer CG, Meyer TF, Miao CY, Miao JY, Michels PA, Michiels C, Mijaljica D, Milojkovic A, Minucci S, Miracco C, Miranti CK, Mitroulis I, Miyazawa K, Mizushima N, Mograbi B, Mohseni S, Molero X, Mollereau B, Mollinedo F, Momoi T, Monastyrska I, Monick MM, Monteiro MJ, Moore MN, Mora R, Moreau K, Moreira PI, Moriyasu Y, Moscat J, Mostowy S, Mottram JC, Motyl T, Moussa CE, Muller S, Muller S, Munger K, Munz C, Murphy LO, Murphy ME, Musaro A, Mysorekar I, Nagata E, Nagata K, Nahimana A, Nair U, Nakagawa T, Nakahira K, Nakano H, Nakatogawa H, Nanjundan M, Naqvi NI, Narendra DP, Narita M, Navarro M, Nawrocki ST, Nazarko TY, Nemchenko A, Netea MG, Neufeld TP, Ney PA, Nezis IP, Nguyen HP, Nie D, Nishino I, Nislow C, Nixon RA, Noda T, Noegel AA, Nogalska A, Noguchi S, Notterpek L, Novak I, Nozaki T, Nukina N, Nurnberger T, Nyfeler B, Obara K, Oberley TD, Oddo S, Ogawa M, Ohashi T, Okamoto K, Oleinick NL, Oliver FJ, Olsen LJ, Olsson S, Opota O, Osborne TF, Ostrander GK, Otsu K, Ou JH, Ouimet M, Overholtzer M, Ozpolat B, Paganetti P, Pagnini U, Pallet N, Palmer GE, Palumbo C, Pan T, Panaretakis T, Pandey UB, Papackova Z, Papassideri I, Paris I, Park J, Park OK, Parys JB, Parzych KR, Patschan S, Patterson C, Pattingre S, Pawelek JM, Peng J, Perlmutter DH, Perrotta I, Perry G, Pervaiz S, Peter M, Peters GJ, Petersen M, Petrovski G, Phang JM, Piacentini M, Pierre P, Pierrefite-Carle V, Pierron G, Pinkas-Kramarski R, Piras A, Piri N, Platanias LC, Poggeler S, Poirot M, Poletti A, Pous C, Pozuelo-Rubio M, Praetorius-Ibba M, Prasad A, Prescott M, Priault M, Produit-Zengaffinen N, Progulske-Fox A, Proikas-Cezanne T, Przedborski S, Przyklenk K, Puertollano R, Puyal J, Qian SB, Qin L, Qin ZH, Quaggin SE, Raben N, Rabinowich H, Rabkin SW, Rahman I, Rami A, Ramm G, Randall G, Randow F, Rao VA, Rathmell JC, Ravikumar B, Ray SK, Reed BH, Reed JC, Reggiori F, Regnier-Vigouroux A, Reichert AS, Reiners JJ Jr, Reiter RJ, Ren J, Revuelta JL, Rhodes CJ, Ritis K, Rizzo E, Robbins J, Roberge M, Roca H, Roccheri MC, Rocchi S, Rodemann HP, Rodriguez de Cordoba S, Rohrer B, Roninson IB, Rosen K, Rost-Roszkowska MM, Rouis M, Rouschop KM, Rovetta F, Rubin BP, Rubinsztein DC, Ruckdeschel K, Rucker EB 3rd, Rudich A, Rudolf E, Ruiz-Opazo N, Russo R, Rusten TE, Ryan KM, Ryter SW, Sabatini DM, Sadoshima J, Saha T, Saitoh T, Sakagami H, Sakai Y, Salekdeh GH, Salomoni P, Salvaterra PM, Salvesen G, Salvioli R, Sanchez AM, Sanchez-Alcazar JA, Sanchez-Prieto R, Sandri M, Sankar U, Sansanwal P, Santambrogio L, Saran S, Sarkar S, Sarwal M, Sasakawa C, Sasnauskiene A, Sass M, Sato K, Sato M, Schapira AH, Scharl M, Schatzl HM, Scheper W, Schiaffino S, Schneider C, Schneider ME, Schneider-Stock R, Schoenlein PV, Schorderet DF, Schuller C, Schwartz GK, Scorrano L, Sealy L, Seglen PO, Segura-Aguilar J, Seiliez I, Seleverstov O, Sell C, Seo JB, Separovic D, Setaluri V, Setoguchi T, Settembre C, Shacka JJ, Shanmugam M, Shapiro IM, Shaulian E, Shaw RJ, Shelhamer JH, Shen HM, Shen WC, Sheng ZH, Shi Y, Shibuya K, Shidoji Y, Shieh JJ, Shih CM, Shimada Y, Shimizu S, Shintani T, Shirihai OS, Shore GC, Sibirny AA, Sidhu SB, Sikorska B, Silva-Zacarin EC, Simmons A, Simon AK, Simon HU, Simone C, Simonsen A, Sinclair DA, Singh R, Sinha D, Sinicrope FA, Sirko A, Rao VA, Rathmell JC, Ravikumar B, Ray SK, Reed BH, Reed JC, Reggiori F, Regnier-Vigouroux A, Reichert AS, Reiners JJ Jr, Reiter RJ, Ren J, Revuelta JL, Rhodes CJ, Ritis K, Rizzo E, Robbins J, Roberge M, Roca H, Roccheri MC, Rocchi S, Rodemann HP, Rodriguez de Cordoba S, Rohrer B, Roninson IB, Rosen K, Rost-Roszkowska MM, Rouis M, Rouschop KM, Rovetta F, Rubin BP, Rubinsztein DC, Ruckdeschel K, Rucker EB 3rd, Rudich A, Rudolf E, Ruiz-Opazo N, Russo R, Rusten TE, Ryan KM, Ryter SW, Sabatini DM, Sadoshima J, Saha T, Saitoh T, Sakagami H, Sakai Y, Salekdeh GH, Salomoni P, Salvaterra PM, Salvesen G, Salvioli R, Sanchez AM, Sanchez-Alcazar JA, Sanchez-Prieto R, Sandri M, Sankar U, Sansanwal P, Santambrogio L, Saran S, Sarkar S, Sarwal M, Sasakawa C, Sasnauskiene A, Sass M, Sato K, Sato M, Schapira AH, Scharl M, Schatzl HM, Scheper W, Schiaffino S, Schneider C, Schneider ME, Schneider-Stock R, Schoenlein PV, Schorderet DF, Schuller C, Schwartz GK, Scorrano L, Sealy L, Seglen PO, Segura-Aguilar J, Seiliez I, Seleverstov O, Sell C, Seo JB, Separovic D, Setaluri V, Setoguchi T, Settembre C, Shacka JJ, Shanmugam M, Shapiro IM, Shaulian E, Shaw RJ, Shelhamer JH, Shen HM, Shen WC, Sheng ZH, Shi Y, Shibuya K, Shidoji Y, Shieh JJ, Shih CM, Shimada Y, Shimizu S, Shintani T, Shirihai OS, Shore GC, Sibirny AA, Sidhu SB, Sikorska B, Silva-Zacarin EC, Simmons A, Simon AK, Simon HU, Simone C, Simonsen A, Sinclair DA, Singh R, Sinha D, Sinicrope FA, Sirko A, Siu PM, Sivridis E, Skop V, Skulachev VP, Slack RS, Smaili SS, Smith DR, Soengas MS, Soldati T, Song X, Sood AK, Soong TW, Sotgia F, Spector SA, Spies CD, Springer W, Srinivasula SM, Stefanis L, Steffan JS, Stendel R, Stenmark H, Stephanou A, Stern ST, Sternberg C, Stork B, Stralfors P, Subauste CS, Sui X, Sulzer D, Sun J, Sun SY, Sun ZJ, Sung JJ, Suzuki K, Suzuki T, Swanson MS, Swanton C, Sweeney ST, Sy LK, Szabadkai G, Tabas I, Taegtmeyer H, Tafani M, Takacs-Vellai K, Takano Y, Takegawa K, Takemura G, Takeshita F, Talbot NJ, Tan KS, Tanaka K, Tanaka K, Tang D, Tang D, Tanida I, Tannous BA, Tavernarakis N, Taylor GS, Taylor GA, Taylor JP, Terada LS, Terman A, Tettamanti G, Thevissen K, Thompson CB, Thorburn A, Thumm M, Tian F, Tian Y, Tocchini-Valentini G, Tolkovsky AM, Tomino Y, Tonges L, Tooze SA, Tournier C, Tower J, Towns R, Trajkovic V, Travassos LH, Tsai TF, Tschan MP, Tsubata T, Tsung A, Turk B, Turner LS, Tyagi SC, Uchiyama Y, Ueno T, Umekawa M, Umemiya-Shirafuji R, Unni VK, Vaccaro MI, Valente EM, Van den Berghe G, van der Klei IJ, van Doorn W, van Dyk LF, van Egmond M, van Grunsven LA, Vandenabeele P, Vandenberghe WP, Vanhorebeek I, Vaquero EC, Velasco G, Vellai T, Vicencio JM, Vierstra RD, Vila M, Vindis C, Viola G, Viscomi MT, Voitsekhovskaja OV, von Haefen C, Votruba M, Wada K, Wade-Martins R, Walker CL, Walsh CM, Walter J, Wan XB, Wang A, Wang C, Wang D, Wang F, Wang F, Wang G, Wang H, Wang HG, Wang HD, Wang J, Wang K, Wang M, Wang RC, Wang X, Wang X, Wang YJ, Wang Y, Wang Z, Wang ZC, Wang Z, Wansink DG, Ward DM, Watada H, Waters SL, Webster P, Wei L, Weihl CC, Weiss WA, Welford SM, Wen LP, Whitehouse CA, Whitton JL, Whitworth AJ, Wileman T, Wiley JW, Wilkinson S, Willbold D, Williams RL, Williamson PR, Wouters BG, Wu C, Wu DC, Wu WK, Wyttenbach A, Xavier RJ, Xi Z, Xia P, Xiao G, Xie Z, Xie Z, Xu DZ, Xu J, Xu L, Xu X, Yamamoto A, Yamamoto A, Yamashina S, Yamashita M, Yan X, Yanagida M, Yang DS, Yang E, Yang JM, Yang SY, Yang W, Yang WY, Yang Z, Yao MC, Yao TP, Yeganeh B, Yen WL, Yin JJ, Yin XM, Yoo OJ, Yoon G, Yoon SY, Yorimitsu T, Yoshikawa Y, Yoshimori T, Yoshimoto K, You HJ, Youle RJ, Younes A, Yu L, Yu L, Yu SW, Yu WH, Yuan ZM, Yue Z, Yun CH, Yuzaki M, Zabirnyk O, Silva-Zacarin E, Zacks D, Zacksenhaus E, Zaffaroni N, Zakeri Z, Zeh HJ 3rd, Zeitlin SO, Zhang H, Zhang HL, Zhang J, Zhang JP, Zhang L, Zhang L, Zhang MY, Zhang XD, Zhao M, Zhao YF, Zhao Y, Zhao ZJ, Zheng X, Zhivotovsky B, Zhong Q, Zhou CZ, Zhu C, Zhu WG, Zhu XF, Zhu X, Zhu Y, Zoladek T, Zong WX, Zorzano A, Zschocke J, Zuckerbraun B (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8(4):445–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klosowiak JL, Park S, Smith KP, French ME, Focia PJ, Freymann DM, Rice SE (2016) Structural insights into Parkin substrate lysine targeting from minimal Miro substrates. Sci Rep 6:33019. doi:10.1038/srep33019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ko HS, von Coelln R, Sriram SR, Kim SW, Chung KK, Pletnikova O, Troncoso J, Johnson B, Saffary R, Goh EL, Song H, Park BJ, Kim MJ, Kim S, Dawson VL, Dawson TM (2005) Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. J Neurosci 25(35):7968–7978. doi:10.1523/JNEUROSCI.2172-05.2005

    Article  CAS  PubMed  Google Scholar 

  • Kohta R, Kotake Y, Hosoya T, Hiramatsu T, Otsubo Y, Koyama H, Hirokane Y, Yokoyama Y, Ikeshoji H, Oofusa K, Suzuki M, Ohta S (2010) 1-Benzyl-1,2,3,4-tetrahydroisoquinoline binds with tubulin beta, a substrate of parkin, and reduces its polyubiquitination. J Neurochem 114(5):1291–1301. doi:10.1111/j.1471-4159.2010.06576.x

    CAS  PubMed  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(7503):162–166. doi:10.1038/nature13392

    CAS  PubMed  Google Scholar 

  • Kubo SI, Kitami T, Noda S, Shimura H, Uchiyama Y, Asakawa S, Minoshima S, Shimizu N, Mizuno Y, Hattori N (2001) Parkin is associated with cellular vesicles. J Neurochem 78(1):42–54

    Article  CAS  PubMed  Google Scholar 

  • Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309(5733):481–484. doi:10.1126/science.1112125

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Aguirre JD, Condos TE, Martinez-Torres RJ, Chaugule VK, Toth R, Sundaramoorthy R, Mercier P, Knebel A, Spratt DE, Barber KR, Shaw GS, Walden H (2015) Disruption of the autoinhibited state primes the E3 ligase parkin for activation and catalysis. EMBO J 34(20):2506–2521. doi:10.15252/embj.201592337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumru H, Santamaria J, Tolosa E, Valldeoriola F, Munoz E, Marti MJ, Iranzo A (2004) Rapid eye movement sleep behavior disorder in parkinsonism with parkin mutations. Ann Neurol 56(4):599–603. doi:10.1002/ana.20272

    Article  CAS  PubMed  Google Scholar 

  • Kurup PK, Xu J, Videira RA, Ononenyi C, Baltazar G, Lombroso PJ, Nairn AC (2015) STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson’s disease. Proc Natl Acad Sci USA 112(4):1202–1207. doi:10.1073/pnas.1417423112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • LaVoie MJ, Cortese GP, Ostaszewski BL, Schlossmacher MG (2007) The effects of oxidative stress on parkin and other E3 ligases. J Neurochem 103(6):2354–2368. doi:10.1111/j.1471-4159.2007.04911.x

    Article  CAS  PubMed  Google Scholar 

  • Leroy E, Anastasopoulos D, Konitsiotis S, Lavedan C, Polymeropoulos MH (1998) Deletions in the Parkin gene and genetic heterogeneity in a Greek family with early onset Parkinson’s disease. Hum Genet 103(4):424–427

    Article  CAS  PubMed  Google Scholar 

  • Lesage S, Magali P, Lohmann E, Lacomblez L, Teive H, Janin S, Cousin PY, Durr A, Brice A, French Parkinson Disease Genetics Study G (2007) Deletion of the parkin and PACRG gene promoter in early-onset parkinsonism. Hum Mutat 28(1):27–32. doi:10.1002/humu.20436

    Article  CAS  PubMed  Google Scholar 

  • Lesage S, Lohmann E, Tison F, Durif F, Durr A, Brice A, French Parkinson’s Disease Genetics Study Group (2008) Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls. J Med Genet 45(1):43–46. doi:10.1136/jmg.2007.051854

    Article  CAS  PubMed  Google Scholar 

  • Lim KL, Chew KC, Tan JM, Wang C, Chung KK, Zhang Y, Tanaka Y, Smith W, Engelender S, Ross CA, Dawson VL, Dawson TM (2005) Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation. J Neurosci 25(8):2002–2009. doi:10.1523/JNEUROSCI.4474-04.2005

    Article  CAS  PubMed  Google Scholar 

  • Lim MK, Kawamura T, Ohsawa Y, Ohtsubo M, Asakawa S, Takayanagi A, Shimizu N (2007) Parkin interacts with LIM Kinase 1 and reduces its cofilin-phosphorylation activity via ubiquitination. Exp Cell Res 313(13):2858–2874. doi:10.1016/j.yexcr.2007.04.016

    Article  CAS  PubMed  Google Scholar 

  • Lincoln SJ, Maraganore DM, Lesnick TG, Bounds R, de Andrade M, Bower JH, Hardy JA, Farrer MJ (2003) Parkin variants in North American Parkinson's disease: cases and controls. Mov Disord 18(11):1306–1311. doi:10.1002/mds.10601

    Article  PubMed  Google Scholar 

  • Liu K, Li F, Han H, Chen Y, Mao Z, Luo J, Zhao Y, Zheng B, Gu W, Zhao W (2016) Parkin regulates the activity of pyruvate kinase M2. J Biol Chem 291(19):10307–10317. doi:10.1074/jbc.M115.703066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lucking CB, Chesneau V, Lohmann E, Verpillat P, Dulac C, Bonnet AM, Gasparini F, Agid Y, Durr A, Brice A (2003) Coding polymorphisms in the parkin gene and susceptibility to Parkinson disease. Arch Neurol 60(9):1253–1256. doi:10.1001/archneur.60.9.1253

    Article  PubMed  Google Scholar 

  • Machida Y, Chiba T, Takayanagi A, Tanaka Y, Asanuma M, Ogawa N, Koyama A, Iwatsubo T, Ito S, Jansen PH, Shimizu N, Tanaka K, Mizuno Y, Hattori N (2005) Common anti-apoptotic roles of parkin and alpha-synuclein in human dopaminergic cells. Biochem Biophys Res Commun 332(1):233–240. doi:10.1016/j.bbrc.2005.04.124

    Article  CAS  PubMed  Google Scholar 

  • Madegowda RH, Kishore A, Anand A (2005) Mutational screening of the parkin gene among South Indians with early onset Parkinson’s disease. J Neurol Neurosurg Psychiatry 76(11):1588–1590. doi:10.1136/jnnp.2004.046888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maruyama M, Ikeuchi T, Saito M, Ishikawa A, Yuasa T, Tanaka H, Hayashi S, Wakabayashi K, Takahashi H, Tsuji S (2000) Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism. Ann Neurol 48(2):245–250

    Article  CAS  PubMed  Google Scholar 

  • Matsuda N, Kitami T, Suzuki T, Mizuno Y, Hattori N, Tanaka K (2006) Diverse effects of pathogenic mutations of Parkin that catalyze multiple monoubiquitylation in vitro. J Biol Chem 281(6):3204–3209. doi:10.1074/jbc.M510393200

    Article  CAS  PubMed  Google Scholar 

  • Matsumine H, Saito M, Shimoda-Matsubayashi S, Tanaka H, Ishikawa A, Nakagawa-Hattori Y, Yokochi M, Kobayashi T, Igarashi S, Takano H, Sanpei K, Koike R, Mori H, Kondo T, Mizutani Y, Schaffer AA, Yamamura Y, Nakamura S, Kuzuhara S, Tsuji S, Mizuno Y (1997) Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27. Am J Hum Genet 60(3):588–596

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matsumine H, Yamamura Y, Hattori N, Kobayashi T, Kitada T, Yoritaka A, Mizuno Y (1998a) A microdeletion of D6S305 in a family of autosomal recessive juvenile parkinsonism (PARK2). Genomics 49(1):143–146. doi:10.1006/geno.1997.5196

    Article  CAS  PubMed  Google Scholar 

  • Matsumine H, Yamamura Y, Kobayashi T, Nakamura S, Kuzuhara S, Mizuno Y (1998b) Early onset parkinsonism with diurnal fluctuation maps to a locus for juvenile parkinsonism. Neurology 50(5):1340–1345

    Article  CAS  PubMed  Google Scholar 

  • Mitsui J, Takahashi Y, Goto J, Tomiyama H, Ishikawa S, Yoshino H, Minami N, Smith DI, Lesage S, Aburatani H, Nishino I, Brice A, Hattori N, Tsuji S (2010) Mechanisms of genomic instabilities underlying two common fragile-site-associated loci, PARK2 and DMD, in germ cell and cancer cell lines. Am J Hum Genet 87(1):75–89. doi:10.1016/j.ajhg.2010.06.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mori H, Kondo T, Yokochi M, Matsumine H, Nakagawa-Hattori Y, Miyake T, Suda K, Mizuno Y (1998) Pathologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q. Neurology 51(3):890–892

    Article  CAS  PubMed  Google Scholar 

  • Muller-Rischart AK, Pilsl A, Beaudette P, Patra M, Hadian K, Funke M, Peis R, Deinlein A, Schweimer C, Kuhn PH, Lichtenthaler SF, Motori E, Hrelia S, Wurst W, Trumbach D, Langer T, Krappmann D, Dittmar G, Tatzelt J, Winklhofer KF (2013) The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO. Mol Cell 49(5):908–921. doi:10.1016/j.molcel.2013.01.036

    Article  PubMed  CAS  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(5):795–803. doi:10.1083/jcb.200809125

    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(1):e1000298. doi:10.1371/journal.pbio.1000298

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Okatsu K, Kimura M, Oka T, Tanaka K, Matsuda N (2015a) Unconventional PINK1 localization to the outer membrane of depolarized mitochondria drives Parkin recruitment. J Cell Sci 128(5):964–978. doi:10.1242/jcs.161000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okatsu K, Koyano F, Kimura M, Kosako H, Saeki Y, Tanaka K, Matsuda N (2015b) Phosphorylated ubiquitin chain is the genuine Parkin receptor. J Cell Biol 209(1):111–128. doi:10.1083/jcb.201410050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oliveira SA, Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons KE, Pahwa R, Stern MB, Hiner BC, Jankovic J, Ondo WG, Allen FH Jr, Scott BL, Goetz CG, Small GW, Mastaglia FL, Stajich JM, Zhang F, Booze MW, Reaves JA, Middleton LT, Haines JL, Pericak-Vance MA, Vance JM, Martin ER (2003) Association study of Parkin gene polymorphisms with idiopathic Parkinson disease. Arch Neurol 60(7):975–980. doi:10.1001/archneur.60.7.975

    Article  PubMed  Google Scholar 

  • Orimo S, Amino T, Yokochi M, Kojo T, Uchihara T, Takahashi A, Wakabayashi K, Takahashi H, Hattori N, Mizuno Y (2005) Preserved cardiac sympathetic nerve accounts for normal cardiac uptake of MIBG in PARK2. Mov Disord 20(10):1350–1353. doi:10.1002/mds.20594

    Article  PubMed  Google Scholar 

  • Palacino JJ, Sagi D, Goldberg MS, Krauss S, Motz C, Wacker M, Klose J, Shen J (2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279(18):18614–18622. doi:10.1074/jbc.M401135200

    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(7097):1157–1161. doi:10.1038/nature04788

    Article  CAS  PubMed  Google Scholar 

  • Periquet M, Lucking C, Vaughan J, Bonifati V, Durr A, De Michele G, Horstink M, Farrer M, Illarioshkin SN, Pollak P, Borg M, Brefel-Courbon C, Denefle P, Meco G, Gasser T, Breteler MM, Wood N, Agid Y, Brice A, French Parkinson’s Disease Genetics Study Group, The European Consortium on Genetic Susceptibility in Parkinson’s Disease (2001) Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from Founder effects. Am J Hum Genet 68(3):617–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pickrell AM, Huang CH, Kennedy SR, Ordureau A, Sideris DP, Hoekstra JG, Harper JW, Youle RJ (2015) Endogenous parkin preserves dopaminergic substantia nigral neurons following mitochondrial DNA mutagenic stress. Neuron 87(2):371–381. doi:10.1016/j.neuron.2015.06.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276(5321):2045–2047

    Article  CAS  PubMed  Google Scholar 

  • Poole AC, Thomas RE, Yu S, Vincow ES, Pallanck L (2010) The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway. PLoS ONE 5(4):e10054. doi:10.1371/journal.pone.0010054

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pramstaller PP, Kis B, Eskelson C, Hedrich K, Scherer M, Schwinger E, Breakefield XO, Kramer PL, Ozelius LJ, Klein C (2002) Phenotypic variability in a large kindred (Family LA) with deletions in the parkin gene. Mov Disord 17(2):424–426

    Article  PubMed  Google Scholar 

  • Pramstaller PP, Schlossmacher MG, Jacques TS, Scaravilli F, Eskelson C, Pepivani I, Hedrich K, Adel S, Gonzales-McNeal M, Hilker R, Kramer PL, Klein C (2005) Lewy body Parkinson’s disease in a large pedigree with 77 Parkin mutation carriers. Ann Neurol 58(3):411–422. doi:10.1002/ana.20587

    Article  CAS  PubMed  Google Scholar 

  • Puschmann A, Fiesel FC, Caulfield TR, Hudec R, Ando M, Truban D, Hou X, Ogaki K, Heckman MG, James ED, Swanberg M, Jimenez-Ferrer I, Hansson O, Opala G, Siuda J, Boczarska-Jedynak M, Friedman A, Koziorowski D, Aasly JO, Lynch T, Mellick GD, Mohan M, Silburn PA, Sanotsky Y, Vilarino-Guell C, Farrer MJ, Chen L, Dawson VL, Dawson TM, Wszolek ZK, Ross OA, Springer W (2017) Heterozygous PINK1 p.G411S increases risk of Parkinson’s disease via a dominant-negative mechanism. Brain 140(Pt 1):98–117. doi:10.1093/brain/aww261

    Article  PubMed  Google Scholar 

  • Sala G, Stefanoni G, Arosio A, Riva C, Melchionda L, Saracchi E, Fermi S, Brighina L, Ferrarese C (2014) Reduced expression of the chaperone-mediated autophagy carrier hsc70 protein in lymphomonocytes of patients with Parkinson’s disease. Brain Res 1546:46–52. doi:10.1016/j.brainres.2013.12.017

    Article  CAS  PubMed  Google Scholar 

  • Sato S, Chiba T, Nishiyama S, Kakiuchi T, Tsukada H, Hatano T, Fukuda T, Yasoshima Y, Kai N, Kobayashi K, Mizuno Y, Tanaka K, Hattori N (2006a) Decline of striatal dopamine release in parkin-deficient mice shown by ex vivo autoradiography. J Neurosci Res 84(6):1350–1357. doi:10.1002/jnr.21032

    Article  CAS  PubMed  Google Scholar 

  • Sato S, Chiba T, Sakata E, Kato K, Mizuno Y, Hattori N, Tanaka K (2006b) 14-3-3eta is a novel regulator of parkin ubiquitin ligase. EMBO J 25(1):211–221. doi:10.1038/sj.emboj.7600774

    Article  CAS  PubMed  Google Scholar 

  • Sauve V, Lilov A, Seirafi M, Vranas M, Rasool S, Kozlov G, Sprules T, Wang J, Trempe JF, Gehring K (2015) A Ubl/ubiquitin switch in the activation of Parkin. EMBO J 34(20):2492–2505. doi:10.15252/embj.201592237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schlitter AM, Kurz M, Larsen JP, Woitalla D, Muller T, Epplen JT, Dekomien G (2006) Parkin gene variations in late-onset Parkinson’s disease: comparison between Norwegian and German cohorts. Acta Neurol Scand 113(1):9–13. doi:10.1111/j.1600-0404.2005.00532.x

    Article  CAS  PubMed  Google Scholar 

  • Sharp ME, Caccappolo E, Mejia-Santana H, Tang MX, Rosado L, Orbe Reilly M, Ruiz D, Louis ED, Comella C, Nance M, Bressman S, Scott WK, Tanner C, Waters C, Fahn S, Cote L, Ford B, Rezak M, Novak K, Friedman JH, Pfeiffer R, Payami H, Molho E, Factor SA, Nutt J, Serrano C, Arroyo M, Pauciulo MW, Nichols WC, Clark LN, Alcalay RN, Marder KS (2015) The relationship between obsessive-compulsive symptoms and PARKIN genotype: the CORE-PD study. Mov Disord 30(2):278–283. doi:10.1002/mds.26065

    Article  CAS  PubMed  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. doi:10.1038/srep01002

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shiba-Fukushima K, Arano T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, Ryu KY, Nukina N, Hattori N, Imai Y (2014) Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering. PLoS Genet 10(12):e1004861. doi:10.1371/journal.pgen.1004861

    Article  PubMed  PubMed Central  Google Scholar 

  • Shimoda-Matsubayashi S, Hattori T, Matsumine H, Shinohara A, Yoritaka A, Mori H, Kondo T, Chiba M, Mizuno Y (1997) Mn SOD activity and protein in a patient with chromosome 6-linked autosomal recessive parkinsonism in comparison with Parkinson’s disease and control. Neurology 49(5):1257–1262

    Article  CAS  PubMed  Google Scholar 

  • Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25(3):302–305. doi:10.1038/77060

    Article  CAS  PubMed  Google Scholar 

  • Shimura H, Schlossmacher MG, Hattori N, Frosch MP, Trockenbacher A, Schneider R, Mizuno Y, Kosik KS, Selkoe DJ (2001) Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson’s disease. Science 293(5528):263–269. doi:10.1126/science.1060627

    Article  CAS  PubMed  Google Scholar 

  • Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, Troconso JC, Dawson VL, Dawson TM (2011) PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson’s disease. Cell 144(5):689–702. doi:10.1016/j.cell.2011.02.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shyu WC, Lin SZ, Chiang MF, Pang CY, Chen SY, Hsin YL, Thajeb P, Lee YJ, Li H (2005) Early-onset Parkinson’s disease in a Chinese population: 99mTc-TRODAT-1 SPECT, Parkin gene analysis and clinical study. Parkinsonism Relat Disord 11(3):173–180. doi:10.1016/j.parkreldis.2004.12.004

    Article  PubMed  Google Scholar 

  • Srivastava A, Tang MX, Mejia-Santana H, Rosado L, Louis ED, Caccappolo E, Comella C, Colcher A, Siderowf A, Jennings D, Nance M, Bressman S, Scott WK, Tanner C, Mickel S, Andrews H, Waters C, Fahn S, Cote L, Frucht S, Ford B, Alcalay RN, Ross B, Orbe Reilly M, Rezak M, Novak K, Friedman JH, Pfeiffer RD, Marsh L, Hiner B, Merle D, Ottman R, Clark LN, Marder K (2011) The relation between depression and parkin genotype: the CORE-PD study. Parkinsonism Relat Disord 17(10):740–744. doi:10.1016/j.parkreldis.2011.07.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sterky FH, Lee S, Wibom R, Olson L, Larsson NG (2011) Impaired mitochondrial transport and Parkin-independent degeneration of respiratory chain-deficient dopamine neurons in vivo. Proc Natl Acad Sci USA 108(31):12937-12942. doi:10.1073/pnas.1103295108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stevens DA, Lee Y, Kang HC, Lee BD, Lee YI, Bower A, Jiang H, Kang SU, Andrabi SA, Dawson VL, Shin JH, Dawson TM (2015) Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration. Proc Natl Acad Sci USA 112(37):11696–11701. doi:10.1073/pnas.1500624112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun M, Latourelle JC, Wooten GF, Lew MF, Klein C, Shill HA, Golbe LI, Mark MH, Racette BA, Perlmutter JS, Parsian A, Guttman M, Nicholson G, Xu G, Wilk JB, Saint-Hilaire MH, DeStefano AL, Prakash R, Williamson S, Suchowersky O, Labelle N, Growdon JH, Singer C, Watts RL, Goldwurm S, Pezzoli G, Baker KB, Pramstaller PP, Burn DJ, Chinnery PF, Sherman S, Vieregge P, Litvan I, Gillis T, MacDonald ME, Myers RH, Gusella JF (2006) Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study. Arch Neurol 63(6):826–832. doi:10.1001/archneur.63.6.826

    Article  PubMed  Google Scholar 

  • Suzuki M, Hattori N, Orimo S, Fukumitsu N, Abo M, Kono Y, Sengoku R, Kurita A, Honda H, Inoue K (2005) Preserved myocardial [123I]metaiodobenzylguanidine uptake in autosomal recessive juvenile parkinsonism: first case report. Mov Disord 20(5):634–636. doi:10.1002/mds.20384

    Article  PubMed  Google Scholar 

  • Takahashi H, Ohama E, Suzuki S, Horikawa Y, Ishikawa A, Morita T, Tsuji S, Ikuta F (1994) Familial juvenile parkinsonism: clinical and pathologic study in a family. Neurology 44(3 Pt 1):437–441

    Article  CAS  PubMed  Google Scholar 

  • Tan LC, Tanner CM, Chen R, Chan P, Farrer M, Hardy J, Langston JW (2003) Marked variation in clinical presentation and age of onset in a family with a heterozygous parkin mutation. Mov Disord 18(7):758–763. doi:10.1002/mds.10432

    Article  PubMed  Google Scholar 

  • Tanaka K (1995) Molecular biology of proteasomes. Mol Biol Rep 21(1):21–26

    Article  CAS  PubMed  Google Scholar 

  • Tanaka K, Suzuki T, Hattori N, Mizuno Y (2004) Ubiquitin, proteasome and parkin. Biochim Biophys Acta 1695(1–3):235–247. doi:10.1016/j.bbamcr.2004.09.026

    Article  CAS  PubMed  Google Scholar 

  • Um JW, Chung KC (2006) Functional modulation of parkin through physical interaction with SUMO-1. J Neurosci Res 84(7):1543–1554. doi:10.1002/jnr.21041

    Article  CAS  PubMed  Google Scholar 

  • Um JW, Min DS, Rhim H, Kim J, Paik SR, Chung KC (2006) Parkin ubiquitinates and promotes the degradation of RanBP2. J Biol Chem 281(6):3595–3603. doi:10.1074/jbc.M504994200

    Article  CAS  PubMed  Google Scholar 

  • Vercammen L, Van der Perren A, Vaudano E, Gijsbers R, Debyser Z, Van den Haute C, Baekelandt V (2006) Parkin protects against neurotoxicity in the 6-hydroxydopamine rat model for Parkinson’s disease. Mol Ther 14(5):716–723. doi:10.1016/j.ymthe.2006.06.009

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Hattori N, Matsumine H, Kobayashi T, Yoshino H, Morioka A, Kitada T, Asakawa S, Minoshima S, Shimizu N, Mizuno Y (1999) Polymorphism in the parkin gene in sporadic Parkinson’s disease. Ann Neurol 45(5):655–658

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Lu R, Ouyang X, Ho MW, Chia W, Yu F, Lim KL (2007) Drosophila overexpressing parkin R275W mutant exhibits dopaminergic neuron degeneration and mitochondrial abnormalities. J Neurosci 27(32):8563–8570. doi:10.1523/JNEUROSCI.0218-07.2007

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Song P, Du L, Tian W, Yue W, Liu M, Li D, Wang B, Zhu Y, Cao C, Zhou J, Chen Q (2011a) Parkin ubiquitinates Drp1 for proteasome-dependent degradation: implication of dysregulated mitochondrial dynamics in Parkinson disease. J Biol Chem 286(13):11649–11658. doi:10.1074/jbc.M110.144238

    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 (2011b) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147(4):893–906. doi:10.1016/j.cell.2011.10.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • West A, Periquet M, Lincoln S, Lucking CB, Nicholl D, Bonifati V, Rawal N, Gasser T, Lohmann E, Deleuze JF, Maraganore D, Levey A, Wood N, Durr A, Hardy J, Brice A, Farrer M, French Parkinson’s Disease Genetics Study Group, the European Consortium on Genetic Susceptibility on Parkinson’s Disease (2002) Complex relationship between Parkin mutations and Parkinson disease. Am J Med Genet 114(5):584–591. doi:10.1002/ajmg.10525

    Article  PubMed  Google Scholar 

  • Wiley J, Lynch T, Lincoln S, Skipper L, Hulihan M, Gosal D, Bisceglio G, Kachergus J, Hardy J, Farrer MJ (2004) Parkinson’s disease in Ireland: clinical presentation and genetic heterogeneity in patients with parkin mutations. Mov Disord 19(6):677–681. doi:10.1002/mds.10703

    Article  PubMed  Google Scholar 

  • Wu RM, Shan DE, Sun CM, Liu RS, Hwu WL, Tai CH, Hussey J, West A, Gwinn-Hardy K, Hardy J, Chen J, Farrer M, Lincoln S (2002) Clinical, 18F-dopa PET, and genetic analysis of an ethnic Chinese kindred with early-onset parkinsonism and parkin gene mutations. Mov Disord 17(4):670–675. doi:10.1002/mds.10184

    Article  PubMed  Google Scholar 

  • Wu RM, Bounds R, Lincoln S, Hulihan M, Lin CH, Hwu WL, Chen J, Gwinn-Hardy K, Farrer M (2005) Parkin mutations and early-onset parkinsonism in a Taiwanese cohort. Arch Neurol 62(1):82–87. doi:10.1001/archneur.62.1.82

    Article  PubMed  Google Scholar 

  • Yabu T, Imamura S, Mohammed MS, Touhata K, Minami T, Terayama M, Yamashita M (2011) Differential gene expression of HSC70/HSP70 in yellowtail cells in response to chaperone-mediated autophagy. FEBS J 278(4):673–685. doi:10.1111/j.1742-4658.2010.07989.x

    Article  CAS  PubMed  Google Scholar 

  • Yamada M, Mizuno Y, Mochizuki H (2005) Parkin gene therapy for alpha-synucleinopathy: a rat model of Parkinson’s disease. Hum Gene Ther 16(2):262–270. doi:10.1089/hum.2005.16.262

    Article  CAS  PubMed  Google Scholar 

  • Yamamura Y, Sobue I, Ando K, Iida M, Yanagi T (1973) Paralysis agitans of early onset with marked diurnal fluctuation of symptoms. Neurology 23(3):239–244

    Article  CAS  PubMed  Google Scholar 

  • Yamamura Y, Kuzuhara S, Kondo K, Yanagi T, Uchida M, Matsumine H, Mizuno Y (1998) Clinical, pathologic and genetic studies on autosomal recessive early-onset parkinsonism with diurnal fluctuation. Parkinsonism Relat Disord 4(2):65–72

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Gao J, Chung KK, Huang H, Dawson VL, Dawson TM (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 USA 97(24):13354–13359. doi:10.1073/pnas.240347797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Hattori, N., Mizuno, Y. Twenty years since the discovery of the parkin gene. J Neural Transm 124, 1037–1054 (2017). https://doi.org/10.1007/s00702-017-1742-7

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