UCP3 - AN UNCOUPLING PROTEIN HOMOLOG EXPRESSED PREFERENTIALLY AND ABUNDANTLY IN SKELETAL-MUSCLE AND BROWN ADIPOSE-TISSUE

Uncoupling proteins (UCPs) are inner mitochondrial membrane transporte rs which dissipate the proton gradient, releasing stored energy as hea t. UCP1 is expressed exclusively in brown adipocytes while UCP2 is exp ressed widely. We now report the molecular cloning of a third uncoupli ng protein homologue, designated UCP3. At the amino acid level, hUCP3 is 71% identical to hUCP2 and 57% identical to hUCP1. UCP3 is distingu ished from UCP1 and UCP2 by its abundant and preferential expression i n skeletal muscle in humans, and brown adipose tissue and skeletal mus cle in rodents. Since skeletal muscle and brown adipose tissue are bel ieved to be important sites for regulated energy expenditure in humans and rodents, respectively, UCP3 may be an important mediator of adapt ive thermogenesis. Since UCP3 is minimally expressed in human heart an d other critical organs, it is a promising target for anti-obesity dru g development aimed at increasing thermogenesis. (C) 1997 Academic Pre ss.