Contribution to the identification and analysis of the mitochondrial uncoupling proteins

This review is primarily focused on the contribution of our laboratory to s tudy of the mitochondrial uncoupling UCPs. The initial stage was the descri ption of a 32-kDa membranous protein specifically induced in brown adipose tissue mitochondria of cold-adapted rats. This protein was then shown by ot hers to be responsible for brown fat thermogenesis and was referred to as t he uncoupling protein-UCP (recently renamed UCP1). cDNA and genomic clones of UCP1 were isolated and used to investigate the topology and functional o rganization of the protein in the membrane and the mechanisms of control of UCP1 gene transcription. Orientation of the transmembrane fragments was pr oposed and specific amino acid residues involved in the inhibition of UCP1 by purine nucleotides were identified in recombinant yeast. A potent enhanc er mediating the response of the UCP1 gene to retinoids and controlling the specific transcription in brown adipocytes was identified using transgenic mice. More recently, we identified UCP2, an UCP homolog widely expressed i n human and rodent tissues we also collaborated to characterize the plant U CP. Although the biochemical activities and physiological roles of the nove l UCPs are not well understood, these recent data stimulate research on mit ochondrial carriers, mitochondrial bioenergetics, and energy expenditure.