Uncoupling protein homologs: Emerging views of physiological function

The widespread occurrence of excess weight and related diseases demands tha t efforts be made to understand energy expenditure from the gene to the who le animal. For some time, it has been understood that mitochondrial oxidati on of fuels generates an electrochemical gradient via outward pumping of pr otons by the electron transport chain, ATP production via F1F0 ATP synthase is then facilitated by the inward flux of protons down the gradient. There is a growing appreciation that a significant portion of the metabolic rate of endotherms is attributable to counteracting "proton leak" (uncoupling), wherein a flux of protons down the electrochemical gradient generates heat independently of ATP production. Proton leak is especially apparent in the rmogenic brown adipose tissue, which expresses a tissue-specific uncoupling protein (UCP1), The recent discovery of widely expressed putative UCP1 hom ologs [UCP2, UCP3, UCP4, UCP5/brain mitochondrial carrier protein-1 (BMCP1) ] raised the possibility that innate proton leak and metabolic rate are reg ulated by UCP1-like proteins. On the basis of current published data, one m ay not exclude the possibility that UCP homologs influence metabolic rate.