title: Mitophagy in cells with mtDNA mutations: being sick is not enough.
abstract: Despite the emergence of autophagy as a key process for mitochondrial quality control, the existence and persistence of pathogenic mtDNA mutations in human disease suggests that the degradation of dysfunctional mitochondria does not occur widely in vivo. During macroautophagy, a double-membraned cup-shaped structure engulfs cytosolic content. This autophagic vesicle then fuses with lysosomes, allowing hydrolytic enzymes to degrade the contents. Mitochondrial autophagy, or mitophagy, is thought to degrade damaged or nonfunctioning mitochondria specifically. The Parkinson disease-related proteins PINK1 (a mitochondrially localized kinase) and PARK2 (PARKIN, a cytosolically-localized E3 ubiquitin ligase) are essential for targeting mitochondria for mitophagy. Upon chemical uncoupling of the mitochondrial transmembrane potential (Δψ(m)), PINK1 located in the mitochondrial outer membrane recruits PARK2 from the cytosol to the mitochondria, followed by delivery of the organelle to the autophagic machinery for degradation.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Rosa L A
authors.initials: RL
authors.lastname: de Vries
authors.forename: Robert W
authors.initials: RW
authors.lastname: Gilkerson
authors.forename: Serge
authors.initials: S
authors.lastname: Przedborski
authors.forename: Eric A
authors.initials: EA
authors.lastname: Schon
mesh_terms: D001343:Autophagy; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D011494:Protein Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D004272:DNA, Mitochondrial; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D000099202:PTEN-Induced Putative Kinase