Parkinsons Disease–Associated Kinase PINK1 Regulates Miro Protein Level and Axonal Transport of Mitochondria 英文参考文献.docVIP

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Parkinsons Disease–Associated Kinase PINK1 Regulates Miro Protein Level and Axonal Transport of Mitochondria 英文参考文献.doc

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Parkinsons Disease–Associated Kinase PINK1 Regulates Miro Protein Level and Axonal Transport of Mitochondria 英文参考文献

Parkinson’sDisease–AssociatedKinasePINK1Regulates MiroProteinLevelandAxonalTransportofMitochondria SongLiu1.,TomoyoSawada2,3.,SeongsooLee1,WendouYu1,GeorgeSilverio1,PhilomenaAlapatt1, IvanMillan4,AliceShen5,WilliamSaxton6,TomokoKanao7,RyosukeTakahashi2,3,NobutakaHattori3,8 , YuzuruImai9*,BingweiLu1* 1Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America, 2Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 3CREST (Core Research for Evolutionary Science and Technology), Japan Science and Technology Agency, Saitama, Japan, 4NeuroscienceProgram,StanfordUniversitySchoolofMedicine,Stanford,California,UnitedStatesofAmerica,5CollegeofArtsandSciences,WashingtonUniversity,St. Louis,Missouri,UnitedStatesofAmerica,6DepartmentofMolecular,Cell,andDevelopmentalBiology,UniversityofCaliforniaSantaCruz,SantaCruz,California,United StatesofAmerica,7ResearchInstituteforDiseasesofOldAge,JuntendoUniversityGraduateSchoolofMedicine,Tokyo,Japan,8DepartmentofNeurology,Juntendo UniversityGraduateSchoolofMedicine,Tokyo,Japan,9DepartmentofNeuroscienceforNeurodegenerativeDisorders,JuntendoUniversityGraduateSchoolofMedicine, Tokyo,Japan Abstract MutationsinPten-inducedkinase1(PINK1)arelinkedtoearly-onsetfamilialParkinson’sdisease(FPD).PINK1haspreviously beenimplicatedinmitochondrialfission/fusiondynamics,qualitycontrol,andelectrontransportchainfunction.However,it is not clear how these processes are interconnected and whether they are sufficient to explain all aspects of PINK1 pathogenesis. Here we show that PINK1 also controls mitochondrial motility. In Drosophila, downregulation of dMiro or other components of the mitochondrial transport machinery rescued dPINK1 mutant phenotypes in the muscle and dopaminergic(DA)neurons,whereasdMirooverexpressionalonecausedDAneuronloss.dMiroproteinlevelwasincreased in dPINK1 mutant but decreased in dPINK1 or dParkin overexpression conditions. In Drosophila larval moto