Mitochondrial Proton Leak and the Uncoupling Proteins |
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Authors: | Jeff A Stuart Kevin M Brindle James A Harper Martin D Brand |
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Institution: | (1) Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK;(2) MRC Dunn Human Nutrition Unit, Hills Rd, Cambridge, CB2 2XY, UK |
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Abstract: | An energetically significant leak of protons occurs across the mitochondrial inner membranesof eukaryotic cells. This seemingly wasteful proton leak accounts for at least 20% of thestandard metabolic rate of a rat. There is evidence that it makes a similar contribution tostandard metabolic rate in a lizard. Proton conductance of the mitochondrial inner membranecan be considered as having two components: a basal component present in all mitochondria,and an augmentative component, which may occur in tissues of mammals and perhaps ofsome other animals. The uncoupling protein of brown adipose tissue, UCP1, is a clear exampleof such an augmentative component. The newly discovered UCP1 homologs, UCP2, UCP3,and brain mitochondrial carrier protein 1 (BMCP1) may participate in the augmentativecomponent of proton leak. However, they do not appear to catalyze the basal leak, as this isobserved in mitochondria from cells which apparently lack these proteins. Whereas UCP1plays an important role in thermogenesis, the evidence that UCP2 and UCP3 do likewiseremains equivocal. |
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Keywords: | Proton leak uncoupling proteins UCP1 UCP2 UCP3 BMCP1 thermogenesis sequence homology mitochondria respiration |
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