Mitochondrial proton leak and the uncoupling proteins

An energetically significant leak of protons occurs across the mitochondria l inner membranes of eukaryotic cells. This seemingly wasteful proton leak accounts for at least 20% of the standard metabolic rate of a rat. There is evidence that it makes a similar contribution to standard metabolic rate i n a lizard. Proton conductance of the mitochondrial inner membrane can be c onsidered as having two components: a basal component present in all mitoch ondria, and an augmentative component, which may occur in tissues of mammal s and perhaps of some other animals. The uncoupling protein of brown adipos e tissue, UCP1, is a clear example of such an augmentative component. The n ewly discovered UCP1 homologs, UCP2, UCP3, and brain mitochondrial carrier protein 1 (BMCP1) may participate in the augmentative component of proton l eak. However, they do not appear to catalyze the basal leak, as this is obs erved in mitochondria from cells which apparently lack these proteins. Wher eas UCP1 plays an important role in thermogenesis, the evidence that UCP2 a nd UCP3 do likewise remains equivocal.