title: Mitochondrial quality control mediated by PINK1 and Parkin: links to parkinsonism.
abstract: Mutations in Parkin or PINK1 are the most common cause of recessive familial parkinsonism. Recent studies suggest that PINK1 and Parkin form a mitochondria quality control pathway that identifies dysfunctional mitochondria, isolates them from the mitochondrial network, and promotes their degradation by autophagy. In this pathway the mitochondrial kinase PINK1 senses mitochondrial fidelity and recruits Parkin selectively to mitochondria that lose membrane potential. Parkin, an E3 ligase, subsequently ubiquitinates outer mitochondrial membrane proteins, notably the mitofusins and Miro, and induces autophagic elimination of the impaired organelles. Here we review the recent rapid progress in understanding the molecular mechanisms of PINK1- and Parkin-mediated mitophagy and the identification of Parkin substrates suggesting how mitochondrial fission and trafficking are involved. We also discuss how defects in mitophagy may be linked to Parkinson's disease.
authors.affiliation: Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Narendra
authors.forename: John E
authors.initials: JE
authors.lastname: Walker
authors.forename: Richard
authors.initials: R
authors.lastname: Youle
mesh_terms: D004789:Enzyme Activation / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D063306:Mitophagy / Q000502:physiology*; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000503:physiopathology*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D020741:rho GTP-Binding Proteins; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein