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PubMed · 11780125

Superoxide activates mitochondrial uncoupling proteins.

Karim S Echtay·Damien Roussel·Julie St-Pierre·Mika B Jekabsons·Susana Cadenas·Jeff A Stuart·James A Harper·Stephen J Roebuck·Alastair Morrison·Susan Pickering·John C Clapham·Martin D Brand
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Abstract

Uncoupling protein 1 (UCP1) diverts energy from ATP synthesis to thermogenesis in the mitochondria of brown adipose tissue by catalysing a regulated leak of protons across the inner membrane. The functions of its homologues, UCP2 and UCP3, in other tissues are debated. UCP2 and UCP3 are present at much lower abundance than UCP1, and the uncoupling with which they are associated is not significantly thermogenic. Mild uncoupling would, however, decrease the mitochondrial production of reactive oxygen species, which are important mediators of oxidative damage. Here we show that superoxide increases mitochondrial proton conductance through effects on UCP1, UCP2 and UCP3. Superoxide-induced uncoupling requires fatty acids and is inhibited by purine nucleotides. It correlates with the tissue expression of UCPs, appears in mitochondria from yeast expressing UCP1, and is absent in skeletal muscle mitochondria from UCP3 knockout mice. Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria.

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Adipose Tissue, BrownAnimalsCarrier ProteinsFood DeprivationGene DeletionGlyburideHot TemperatureIntracellular MembranesIon ChannelsIslets of LangerhansKidneyLiverMembrane PotentialsMembrane ProteinsMembrane Transport ProteinsMiceMice, KnockoutMitochondriaMitochondrial ProteinsMuscle, SkeletalMyocardiumProteinsProtonsRatsReactive Oxygen SpeciesSaccharomyces cerevisiaeSpleenSuperoxidesUncoupling AgentsUncoupling Protein 1Uncoupling Protein 2Uncoupling Protein 3Journal Article

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Karim S Echtay, Damien Roussel, Julie St-Pierre, Mika B Jekabsons, Susana Cadenas, Jeff A Stuart, James A Harper, Stephen J Roebuck, Alastair Morrison, Susan Pickering, John C Clapham, Martin D Brand. 2002-01-03. Superoxide activates mitochondrial uncoupling proteins.. https://doi.org/10.1038/415096a

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