title: Parkin structure and function.
abstract: Mutations in the parkin or PINK1 genes are the leading cause of the autosomal recessive form of Parkinson's disease. The gene products, the E3 ubiquitin ligase parkin and the serine/threonine kinase PINK1, are neuroprotective proteins, which act together in a mitochondrial quality control pathway. Here, we review the structure of parkin and mechanisms of its autoinhibition and function as a ubiquitin ligase. We present a model for the recruitment and activation of parkin as a key regulatory step in the clearance of depolarized or damaged mitochondria by autophagy (mitophagy). We conclude with a brief overview of other functions of parkin and considerations for drug discovery in the mitochondrial quality control pathway.
authors.affiliation: Department of Biochemistry and the Groupe de Recherche axé sur la Structure des Protéines, McGill University, Montréal, Québec, Canada.
authors.forename: Marjan
authors.initials: M
authors.lastname: Seirafi
authors.affiliation: Department of Biochemistry and the Groupe de Recherche axé sur la Structure des Protéines, McGill University, Montréal, Québec, Canada.
authors.forename: Guennadi
authors.initials: G
authors.lastname: Kozlov
authors.affiliation: Department of Biochemistry and the Groupe de Recherche axé sur la Structure des Protéines, McGill University, Montréal, Québec, Canada.
authors.forename: Kalle
authors.initials: K
authors.lastname: Gehring
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D063306:Mitophagy; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology; D010300:Parkinson Disease / Q000201:enzymology* / Q000473:pathology; D021381:Protein Transport; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: PINK1; mitophagy; parkin; ubiquitin; ubiquitination