The uncoupling proteins (UCPs) are thought to uncouple oxidative phosphorylation in the mitochondria and thus generate heat. One of the UCP isoforms, UCP3, is abun-dantly expressed in skeletal muscle, the major thermogenic tissue in humans. UCP3 has been overexpressed at high levels inyeast systems,where it leads to theuncouplingof cell respiration, suggesting that UCP3may indeed be capable of dissipating the mitochondrial proton gradient.