title: PINK1/Parkin-mediated mitophagy in mammalian cells.
abstract: Mitochondria-specific autophagy (mitophagy) is a fundamental process critical for maintaining mitochondrial fitness in a myriad of cell types. Particularly, mitophagy contributes to mitochondrial quality control by selectively eliminating dysfunctional mitochondria. In mammalian cells, the Ser/Thr kinase PINK1 and the E3 ubiquitin ligase Parkin act cooperatively in sensing mitochondrial functional state and marking damaged mitochondria for disposal via the autophagy pathway. Notably, ubiquitin and deubiquitinases play vital roles in modulating Parkin activity and mitophagy efficiency. In this review, we highlight recent breakthroughs addressing the key issues of how PINK1 activates Parkin in response to mitochondrial malfunction, how Parkin localizes specifically to impaired mitochondria, and how ubiquitination and deubiquitination regulate PINK1/Parkin-mediated mitophagy.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Eiyama
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan. Electronic address: kokamoto@fbs.osaka-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Okamoto
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D008322:Mammals; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D063306:Mitophagy; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism; D054875:Ubiquitination; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D064570:Ubiquitin-Specific Proteases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein