title: Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control.
abstract: Mitochondria, which convert energy for the cell, accumulate damage with age, and the resulting mitochondrial dysfunction has been linked to the development of degenerative diseases and aging. To curb the accumulation of damaged mitochondria, the cell has elaborated a number of mitochondrial quality control processes. We describe recent work suggesting that Parkin and PTEN-induced putative kinase 1 (PINK1), two gene products linked to familial forms of parkinsonism, may constitute one of the cell's mitochondrial quality control pathways-identifying impaired mitochondria and selectively trimming them from the mitochondrial network by mitophagy. In particular, we discuss the regulation of PINK1 protein expression and Parkin localization by the bioenergetic status of individual mitochondria; the mechanism by which PINK1 recruits Parkin to the outer mitochondrial membrane; and Parkin's promotion of mitophagy through its ubiquitination of outer mitochondrial membrane proteins. This recent work suggests that Parkin and PINK1 may be among the first mammalian proteins identified with a direct role in regulating mitophagy, and implicate a failure of mitophagy in the pathogenesis of 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 P
authors.initials: DP
authors.lastname: Narendra
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Youle
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000099202:PTEN-Induced Putative Kinase
chemical_list: D024101:Mitochondrial Proteins; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein