The mitochondrial uncoupling proteins

The coupling of oxygen consumption to ADP phosphorylation in mitochondria is rather partial. This is particularly obvious in brown adipocyte mitochondria which use a regulated uncoupling mechanism generating heat production from substrate oxidation. In brown adipose tissue, the uncoupling mechanism is related to a specific protein in the inner mitochondrial membrane refered teas uncoupling protein 1 or UCP1. Ucp1 gene disruption in mice confirmed its role in cold-induced thermogenesis. Genetic analysis of various human cohorts suggested a weak contribution of UCP1 to control of fat content and body weight. The recent cloning of UCP2 and UCP3, two homologues of UCP1, has renewed the field of research on the importance of respiration control in metabolic processes, metabolic diseases and energy balance. Ucp2 is widely expressed in organs whereas Ucp3 is mainly present in skeletal muscles. The chromosomal localization of UCP2 as well as Ucp2 mRNA induction by hyperlipidic diet in mice resistant to obesity led to propose a role for UCP2 in diet-induced thermogenesis. A strong linkage between markers in the vicinity of human UCP2 and UCP3 ( which are adjacent genes) and resting metabolic rate was calculated. Although the family of UCPs participates to basal and regulatory thermogenesis, the exact biochemical and physiological functions of known and novel UCPs, remain to be demonstrated. The UCPs represent new targets for drugs modulating substrate oxidation and body weight.