Contribution to the Identification and Analysis of the Mitochondrial Uncoupling Proteins

This review is primarily focused on the contribution of our laboratory to study of themitochondrial uncoupling UCPs. The initial stage was the description of a 32-kDamembranous protein specifically induced in brown adipose tissue mitochondria of cold-adaptedrats. This protein was then shown by others to be responsible for brown fat thermogenesisand was referred to as the uncoupling protein-UCP (recently renamed UCP1). cDNA andgenomic clones of UCP1 were isolated and used to investigate the topology and functionalorganization of the protein in the membrane and the mechanisms of control of UCP1 genetranscription. Orientation of the transmembrane fragments was proposed and specificamino acid residues involved in the inhibition of UCP1 by purine nucleotides wereidentified in recombinant yeast. A potent enhancer mediating the response of the UCP1gene to retinoids and controlling the specific transcription in brown adipocytes wasidentified using transgenic mice. More recently, we identified UCP2, an UCP homologwidely expressed in human and rodent tissues we also collaborated to characterize theplant UCP. Although the biochemical activities and physiological roles of the novel UCPsare not well understood, these recent data stimulate research on mitochondrial carriers,mitochondrial bioenergetics, and energy expenditure.