title: Genetic mutations and functions of PINK1.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease. Mutations in PINK1 (PARK6) are the second most frequent cause of autosomal recessive, young-onset PD, after parkin (PARK2). PINK1 (a kinase with an N-terminal mitochondrial targeting sequence) provides protection against mitochondrial dysfunction and regulates mitochondrial morphology via fission/fusion machinery. PINK1 also acts upstream of parkin (a cytosolic E3 ubiquitin ligase) in a common pathway. Recent studies have described PINK1/parkin function in the maintenance of mitochondrial quality via autophagy (mitophagy). PINK1/parkin-mediated mitophagy provides new insights into the etiology of PD and could be a suitable target for new treatment of PD. In this review, we discuss the molecular genetics and functions of PINK1, which could be key factors in novel rational therapy for sporadic PD as well as PINK1-linked PD.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Tokyo, 113-8421, Japan.
authors.forename: Sumihiro
authors.initials: S
authors.lastname: Kawajiri
authors.forename: Shinji
authors.initials: S
authors.lastname: Saiki
authors.forename: Shigeto
authors.initials: S
authors.lastname: Sato
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000818:Animals; D006801:Humans; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase