Rapid turnover of mitochondrial uncoupling protein 3.

TitleRapid turnover of mitochondrial uncoupling protein 3.
Publication TypeJournal Article
Year of Publication2010
AuthorsAzzu, V, Mookerjee, SA, Brand, MD
JournalBiochem J
Volume426
Issue1
Pagination13-7
Date Published2010 Jan 27
ISSN1470-8728
KeywordsAdipose Tissue, Brown, Animals, Cell Line, Female, Immunoblotting, Ion Channels, Mice, Mitochondrial Proteins, Muscle, Skeletal, Proteasome Endopeptidase Complex, Rats, Rats, Wistar, Uncoupling Protein 3
Abstract

UCP3 (uncoupling protein 3) and its homologues UCP2 and UCP1 are regulators of mitochondrial function. UCP2 is known to have a short half-life of approx. 1 h, owing to its rapid degradation by the cytosolic 26S proteasome, whereas UCP1 is turned over much more slowly by mitochondrial autophagy. In the present study we investigate whether UCP3 also has a short half-life, and whether the proteasome is involved in UCP3 degradation. UCP3 half-life was examined in the mouse C2C12 myoblast cell line by inhibiting protein synthesis with cycloheximide and monitoring UCP3 protein levels by immunoblot analysis. We show that UCP3 has a short half-life of 0.5-4 h. Rapid degradation was prevented by a cocktail of proteasome inhibitors, supporting a proteasomal mechanism for turnover. In addition, this phenotype is recapitulated in vitro: UCP3 was degraded in mitochondria isolated from rat skeletal muscle or brown adipose tissue with a half-life of 0.5-4 h, but only in the presence of a purified 26S proteasomal fraction. This in vitro proteolysis was also sensitive to proteasome inhibition. This phenotype is in direct contrast with the related proteins UCP1 and the adenine nucleotide translocase, which have long half-lives. Therefore UCP3 is turned over rapidly in multiple cell types in a proteasome-dependent manner.

DOI10.1042/BJ20091321
Alternate JournalBiochem. J.
Citation Key10.1042/BJ20091321
PubMed ID19954423
PubMed Central IDPMC3661275
Grant ListPL1 AG032118 / AG / NIA NIH HHS / United States
P01 AG025901 / AG / NIA NIH HHS / United States
MC_U105663137 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
P30 AG025708 / AG / NIA NIH HHS / United States