Article

Journal of Bioenergetics and Biomembranes

, Volume 31, Issue 5, pp 407-418

First online:

Contribution to the Identification and Analysis of the Mitochondrial Uncoupling Proteins

  • Daniel RicquierAffiliated withCentre de Recherche sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique-Unit 9078 Email author 
  • , Bruno MirouxAffiliated withCentre de Recherche sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique-Unit 9078
  • , Anne-Marie Cassard-DoulcierAffiliated withCentre de Recherche sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique-Unit 9078
  • , Corinne Lévi-MeyrueisAffiliated withCentre de Recherche sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique-Unit 9078
  • , Chantal GellyAffiliated withCentre de Recherche sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique-Unit 9078
  • , Serge RaimbaultAffiliated withCentre de Recherche sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique-Unit 9078
  • , Frédéric BouillaudAffiliated withCentre de Recherche sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique-Unit 9078

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Abstract

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.

Mitochondria uncoupling UCP thermogenesis brown adipose tissue fatty acid oxidation mitochondrial carrier membrane transport