Affiliation:
1. MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK
2. Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA
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 ubiqbiquitiuitin mutants, 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.
Publisher
The Company of Biologists
Cited by
106 articles.
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