Department of Pediatrics, West China Second University Hospital, Sichuan University/Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Chengdu 610041, China
Abstract As a kind of mitochondrial membrane protein with protein kinase activity, phosphatase and tensin homolog deleted on chromosome ten induced kinase 1 (PINK1) is involved in many biological metabolic processes. Since PINK1 had been found to be associated with Parkinson's disease, researchers have been exploring its biological function. PINK1 localizes in the outer mitochondrial membrane and regulates cell function through phosphorylating proteins. PINK1 is involved in mitochondrial function, mitochondrial morphology and mitochondrial autophagy, but the regulatory pathway is not yet clear. PINK1 is expressed widely in many tissues with a variety of biological activity, especially in tissues with high energy consumption. It may therefore be involved in the development and regulation of many diseases. Mutations in PINK1 were originally discovered to cause autosomal recessive Parkinson's disease. Recently some research has revealed that PINK1 is related to the development of neonatal hypoxic-ischemic encephalopathy, cancer, diabetes and other diseases. Studying and exploring the biological functions of PINK1 will facilitate the identification of the targets for therapeutic intervention for its related diseases. This review article mainly focuses on recent studies about the biological function and related diseases of PINK1.
Kawajiri S,Saiki S,Sato S,et al.Genetic mutations and functions of PINK1[J].Trends Pharmacol Sci,2011,32(10):573-580.
[2]
Pickrell AM,Youle RJ.The roles of PINK1,parkin,and mitochondrial fidelity in Parkinson's disease[J].Neuron,2015,85(2):257-273.
[3]
Durcan TM,Fon EA.The three ‘P’s of mitophagy:PARKIN,PINK1,and post-translational modifications[J].Genes Dev,2015,29(10):989-999.
[4]
Puschmann A.Monogenic Parkinson's disease and parkinsonism:clinical phenotypes and frequencies of known mutations[J].Parkinsonism Relat Disord,2013,19(4):407-415.
[5]
Zhou C,Huang Y,Shao Y,et al.The kinase domain of mitochondrial PINK1 faces the cytoplasm[J].Proc Natl Acad Sci U S A,2008,105(33):12022-12027.
[6]
Trempe JF,Fon EA.Structure and function of parkin,PINK1,and DJ-1,the three musketeers of neuroprotection[J].Front Neurol,2013,4:38.
[7]
Sim CH,Gabriel K,Mills RD,et al.Analysis of the regulatory and catalytic domains of PTEN-induced kinase-1(PINK1)[J].Hum Mutat,2012,33(10):1408-1422.
[8]
Wust R,Maurer B,Hauser K,et al.Mutation analyses and association studies to assess the role of the presenilin-associated rhomboid-like gene in Parkinson's disease[J].Neurobiol Aging,2016,39:217 el3-el5.
[9]
Bandres-Ciga S,Mencacci NE,Duran R,et al.Analysis of the genetic variability in Parkinson's disease from Southern Spain[J].Neurobiol Aging,2016,37:210 el-e5.
[10]
Ye M,Zhou D,Zhou Y,et al.Parkinson's disease-associated PINK1 G309D mutation increases abnormal phosphorylation of Tau[J].IUBMB Life,2015,67(4):286-290.
[11]
Rub C,Schroder N,Voos W.Biochemical properties of the kinase PINK1 as sensor protein for mitochondrial damage signalling[J].Biochem Soc Trans,2015,43(2):287-291.
[12]
Roth JA.Correlation between the biochemical pathways altered by mutated parkinson-related genes and chronic exposure to manganese[J].Neurotoxicology,2014,44:314-325.
[13]
Kim H,Yang J,Kim MJ,et al.Tumor necrosis factor receptor-associated protein 1(TRAP1) mutation and TRAP1 inhibitor gamitrinib-triphenylphosphonium (G-TPP) induce a forkhead box O (FOXO)-dependent cell protective signal from mitochondria[J].J Biol Chem,2016,291(4):1841-1853.
Sauve V,Lilov A,Seirafi M,et al.A Ubl/ubiquitin switch in the activation of Parkin[J].EMBO J,2015,34(20):2492-2505.
[16]
Luz AL,Rooney JP,Kubik LL,et al.Mitochondrial morphology and fundamental parameters of the mitochondrial respiratory chain are altered in caenorhabditis elegans strains deficient in mitochondrial dynamics and homeostasis processes[J].PLoS One,2015,10(6):e0130940.
[17]
Yacobi-Sharon K,Namdar Y,Arama E.Alternative germ cell death pathway in Drosophila involves HtrA2/Omi,lysosomes,and a caspase-9 counterpart[J].Dev Cell,2013,25(1):29-42.
[18]
Murata H,Sakaguchi M,Jin Y,et al.A new cytosolic pathway from a Parkinson disease-associated kinase,BRPK/PINK1:activation of AKT via mTORC2[J].J Biol Chem,2011,286(9):7182-7189.
[19]
Haque ME,Mount MP,Safarpour F,et al.Inactivation of Pink1 gene in vivo sensitizes dopamine-producing neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and can be rescued by autosomal recessive Parkinson disease genes,Parkin or DJ-1[J].J Biol Chem,2012,287(27):23162-23170.
[20]
Martella G,Madeo G,Maltese M,et al.Exposure to low-dose rotenone precipitates synaptic plasticity alterations in PINK1 heterozygous knockout mice[J].Neurobiol Dis,2016,91:21-36.
[21]
Haque ME,Thomas KJ,D'Souza C,et al.Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP[J].Proc Natl Acad Sci U S A,2008,105(5):1716-1721.
[22]
Deng H,Jankovic J,Guo Y,et al.Small interfering RNA targeting the PINK1 induces apoptosis in dopaminergic cells SH-SY5Y[J].Biochem Biophys Res Commun,2005,337(4):1133-1138.
[23]
Park J,Lee SB,Lee S,et al.Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin[J].Nature,2006,441(7097):1157-1161.
[24]
Morais VA,Verstreken P,Roethig A,et al.Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function[J].EMBO Mol Med,2009,1(2):99-111.
[25]
Amo T,Sato S,Saiki S,et al.Mitochondrial membrane potential decrease caused by loss of PINK1 is not due to proton leak,but to respiratory chain defects[J].Neurobiol Dis,2011,41(1):111-118.
[26]
Amo T,Saiki S,Sawayama T,et al.Detailed analysis of mitochondrial respiratory chain defects caused by loss of PINK1[J].Neurosci Lett,2014,580:37-40.
[27]
Dai H,Deng Y,Zhang J,et al.PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells[J].Toxicology,2015,334:72-80.
[28]
Akundi RS,Zhi L,Sullivan PG,et al.Shared and cell type-specific mitochondrial defects and metabolic adaptations in primary cells from PINK1-deficient mice[J].Neurodegener Dis,2013,12(3):136-149.
[29]
van der Merwe C,van Dyk HC,Engelbrecht L,et al.Curcumin rescues a PINK1 knock down SH-SY5Y cellular model of Parkinson's disease from mitochondrial dysfunction and cell death[J].Mol Neurobiol,2016.[Epub ahead of print].
[30]
van der Merwe C,Jalali Sefid Dashti Z,Christoffels A,et al.Evidence for a common biological pathway linking three Parkinson's disease-causing genes:parkin,PINK1 and DJ-1[J].Eur J Neurosci,2015,41(9):1113-1125.
[31]
Norris KL,Hao R,Chen LF,et al.Convergence of parkin,PINK1,and alpha-synuclein on stress-induced mitochondrial morphological remodeling[J].J Biol Chem,2015,290(22):13862-13874.
[32]
Lutz AK,Exner N,Fett ME,et al.Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation[J].J Biol Chem,2009,284(34):22938-22951.
[33]
Zhao Y,Chen F,Chen S,et al.The Parkinson's disease-associated gene PINK1 protects neurons from ischemic damage by decreasing mitochondrial translocation of the fission promoter Drp1[J].J Neurochem,2013,127(5):711-722.
[34]
Okatsu K,Oka T,Iguchi M,et al.PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria[J].Nat Commun,2012,3:1016.
Nezich CL,Wang C,Fogel AI,et al.MiT/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5[J].J Cell Biol,2015,210(3):435-450.
[37]
Vincow ES,Merrihew G,Thomas RE,et al.The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo[J].Proc Natl Acad Sci U S A,2013,110(16):6400-6405.
[38]
Rakovic A,Shurkewitsch K,Seibler P,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].J Biol Chem,2013,288(4):2223-2237.
[39]
Okatsu K,Saisho K,Shimanuki M,et al.p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria[J].Genes Cells,2010,15(8):887-900.
[40]
Narendra D,Kane LA,Hauser DN,et al.p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy;VDAC1 is dispensable for both[J].Autophagy,2010,6(8):1090-1106.
[41]
Gegg ME,Cooper JM,Chau KY,et al.Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy[J].Hum Mol Genet,2010,19(24):4861-4870.
[42]
Zhang HT,Mi L,Wang T,et al.PINK1/Parkin-mediated mitophagy play a protective role in manganese induced apoptosis in SH-SY5Y cells[J].Toxicol In Vitro,2016,34:212-219.
[43]
Garber K.Parkinson's disease and cancer:the unexplored connection[J].J Natl Cancer Inst,2010,102(6):371-374.
[44]
Morris LG,Veeriah S,Chan TA.Genetic determinants at the interface of cancer and neurodegenerative disease[J].Oncogene,2010,29(24):3453-3464.
[45]
Plun-Favreau H,Lewis PA,Hardy J,et al.Cancer and neurodegeneration:between the devil and the deep blue sea[J].PLoS Genet,2010,6(12):el001257.
[46]
Tabares-Seisdedos R,Rubenstein JL.Inverse cancer comorbidity:a serendipitous opportunity to gain insight into CNS disorders[J].Nat Rev Neurosci,2013,14(4):293-304.
[47]
Berthier A,Navarro S,Jimenez-Sainz J,et al.PINK1 displays tissue-specific subcellular location and regulates apoptosis and cell growth in breast cancer cells[J].Hum Pathol,2011,42(1):75-87.
Puyal J,Vaslin A,Mottier V,et al.Postischemic treatment of neonatal cerebral ischemia should target autophagy[J].Ann Neurol,2009,66(3):378-389.
[50]
Wang JY,Xia Q,Chu KT,et al.Severe global cerebral ischemia-induced programmed necrosis of hippocampal CA1 neurons in rat is prevented by 3-methyladenine:a widely used inhibitor of autophagy[J].J Neuropathol Exp Neurol,2011,70(4):314-322.