The uncoupling proteins, a review

The uncoupling protein-1 (UCP1), cloned in 1985 (1– 4) and called UCP until 1997, is an inner mitochondrial membrane protein (5) expressed exclusively in the brown adipocyte (6–8). It dissipates the mitochondrial proton (H) gradient generated by the respiratory chain, producing heat instead of ATP (8, 9). In rodents the brown adipose tissue (BAT) contributes to both the maintenance of body temperature in a cold environment through nonshivering thermogenesis and the control of body weight through the regulatory (or facultative) part of diet-induced thermogenesis (10, 11). It has been shown that during cold acclimation the capacity of brown adipocytes to produce heat is determined by the UCP1 content of their mitochondria (12–14). Several observations led to the hypothesis that there could exist uncoupling proteins in tissues other than BAT. First, adult humans, who possess very little active BAT (15, 16), produce heat in their skeletal muscle in response to glucose or catecholamine administration (17–20). Secondly, mitochondrial H leaks have been observed in tissues devoid of UCP1 (21–23). They may account for up to 50% of the oxygen consumption of some tissues (24, 25), and up to 30% of whole body metabolic rate in the rat (24–26). It was suggested that the H leak was related to resting metabolic rate (27, 28). Supporting the previous observations, several groups independently cloned novel UCPs, i.e. UCP2 (29–31) and UCP3 (31, 32). UCP2 is expressed in most tissues studied in humans and rodents, and UCP3 mainly in skeletal muscle in humans, and BAT and skeletal muscle in rodents (31). UCP1, which was thought to be a protein unique to BAT, is in fact a member of an emerging family of uncoupling proteins expressed in humans and animals, and even in plants (33, 34).