Degradation of an intramitochondrial protein by the cytosolic proteasome.

TitleDegradation of an intramitochondrial protein by the cytosolic proteasome.
Publication TypeJournal Article
Year of Publication2010
AuthorsAzzu, V, Brand, MD
JournalJ Cell Sci
Volume123
IssuePt 4
Pagination578-85
Date Published2010 Feb 15
ISSN1477-9137
KeywordsAnimals, Cell Line, Cell-Free System, Cytosol, Energy Metabolism, In Vitro Techniques, Ion Channels, Mitochondrial Proteins, Models, Biological, Mutation, Proteasome Endopeptidase Complex, Proteasome Inhibitors, Proton-Motive Force, Rats, RNA, Small Interfering, Ubiquitin, Uncoupling Protein 2
Abstract

Mitochondrial uncoupling protein 2 (UCP2) is implicated in a wide range of pathophysiological processes, including immunity and diabetes mellitus, but its rapid degradation remains uncharacterized. Using pharmacological proteasome inhibitors, immunoprecipitation, dominant negative ubiquitin mutants, [corrected] cellular fractionation and siRNA techniques, we demonstrate the involvement of the ubiquitin-proteasome system in the rapid degradation of UCP2. Importantly, we resolve the issue of whether intramitochondrial proteins can be degraded by the cytosolic proteasome by reconstituting a cell-free system that shows rapid proteasome-inhibitor-sensitive UCP2 degradation in isolated, energised mitochondria presented with an ATP regenerating system, ubiquitin and 26S proteasome fractions. These observations provide the first demonstration that a mitochondrial inner membrane protein is degraded by the cytosolic ubiquitin-proteasome system.

DOI10.1242/jcs.060004
Alternate JournalJ. Cell. Sci.
Citation Key10.1242/jcs.060004
PubMed ID20103532
PubMed Central IDPMC2818195
Grant ListMC_U105663137 / / Medical Research Council / United Kingdom
P01 AG025901 / AG / NIA NIH HHS / United States
P30 AG025708 / AG / NIA NIH HHS / United States
PL1 AG032118 / AG / NIA NIH HHS / United States