Contributions of studies on uncoupling proteins to research on metabolic diseases

The coupling of O-2 consumption to ADP phosphorylation in mitochondria is p artial. This is particularly obvious in brown adipocyte mitochondria which use a regulated uncoupling mechanism generating heat production from substr ate oxidation, and catalysing thermogenesis in rodents or infants in respon se to cold, and arousing hibernators. In the case of brown adipose tissue, the uncoupling mechanism is related to a specific protein in the inner mito chondrial membrane referred to as UCP1. Although the biological importance of UCP1 in human adults is not demonstrated, genetic analysis of various hu man cohorts suggested a participation of UCP1 to control of fat content and body weight. Very recently, the cloning of UCP2 and UCP3, two homologues o f UCP1, has renewed the field of research on the importance of respiration control in metabolic processes and metabolic diseases, UCP2 is widely expre ssed in organs, whereas UCP3 is mainly present in muscles, These proteins m ay explain why the coupling of respiration to ADP phosphorylation is less t han perfect. Their biological importance should be studied. They also repre sent new putative targets for drugs against metabolic diseases such as obes ity.