title: Regulating mitochondrial outer membrane proteins by ubiquitination and proteasomal degradation.
abstract: Mitochondrial outer membrane proteins have been found to be ubiquitinated and degraded by the proteasome. This process shares at least one component of the ERAD pathway of ER membrane protein degradation, the AAA ATPase cdc48/p97/VCP, thought to extract integral membrane proteins from the lipid bilayer and chaperone them to the proteasome. Proteasomal degradation of the outer mitochondrial membrane (OMM) protein Mcl1 regulates apoptosis whereas Parkin-mediated ubiquitination and degradation of Mitofusins can inhibit mitochondrial fusion and promote mitophagy. The breadth of OMM ubiquitin/proteasome substrates and the physiological relevance of their turnover are only beginning to be understood.
authors.affiliation: Center for Biomedical Engineering and Technology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. mkarbowski@umaryland.edu
authors.forename: Mariusz
authors.initials: M
authors.lastname: Karbowski
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Youle
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination; D015003:Yeasts / Q000166:cytology / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex