Production of endogenous matrix superoxide from mitochondrial complex I leads to activation of uncoupling protein 3.

TitleProduction of endogenous matrix superoxide from mitochondrial complex I leads to activation of uncoupling protein 3.
Publication TypeJournal Article
Year of Publication2004
AuthorsTalbot, DA, Lambert, AJ, Brand, MD
JournalFEBS Lett
Volume556
Issue1-3
Pagination111-5
Date Published2004 Jan 02
ISSN0014-5793
KeywordsAnimals, Carrier Proteins, Electron Transport Complex I, Guanosine Diphosphate, Hydrogen Peroxide, Ion Channels, Kinetics, Male, Membrane Potentials, Mitochondria, Muscle, Mitochondrial Proteins, Oxygen Consumption, Protons, Rats, Rats, Wistar, Rotenone, Succinic Acid, Superoxides, Uncoupling Protein 3, Vitamin E
Abstract

Superoxide generated using exogenous xanthine oxidase indirectly activates an uncoupling protein (UCP)-mediated proton conductance of the mitochondrial inner membrane. We investigated whether endogenous mitochondrial superoxide production could also activate proton conductance. When respiring on succinate, rat skeletal muscle mitochondria produced large amounts of matrix superoxide. Addition of GDP to inhibit UCP3 markedly inhibited proton conductance and increased superoxide production. Both superoxide production and the GDP-sensitive proton conductance were suppressed by rotenone plus an antioxidant. Thus, endogenous superoxide can activate the proton conductance of UCP3, which in turn limits mitochondrial superoxide production. These observations provide a departure point for studies under more physiological conditions.

DOI10.1016/s0014-5793(03)01386-3
Alternate JournalFEBS Lett.
Citation Key10.1016/s0014-5793(03)01386-3
PubMed ID14706836