UCPs, at the interface between bioenergetics and metabolism.
The first member of the uncoupling protein (UCP) family, brown adipose tissue uncoupling protein 1 (UCP1), was identified in 1976. Twenty years later, two closely related proteins, UCP2 and UCP3, were described in mammals. Homologs of these proteins exist in other organisms, including plants. Uncoupling refers to a deterioration of energy conservation between substrate oxidation and ADP phosphorylation. Complete energy conservation loss would be fatal but fine-tuning can be beneficial for processes such as thermogenesis, redox control, and prevention of mitochondrial ROS release. The coupled/uncoupled state of mitochondria is related to the permeability of the inner membrane and the proton transport mediated by activated UCPs underlies the uncoupling activity of these proteins. Proton transport by UCP1 is activated by fatty acids and this ensures thermogenesis. In vivo in absence of this activation UCP1 remains inhibited with no transport activity. A similar situation now seems unlikely for UCP2 and UCP3 and while activation of their proton transport has been described its physiological relevance remains uncertain and their influence can be envisaged as a result of another transport pathway that takes place in the absence of activation. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
Inserm U1016, Institut Cochin, 75014 Paris Cedex, France; CNRS UMR 8104, 75014 Paris Cedex, France; Université Paris Descartes UMRS1016, 75014 Paris Cedex, France. Electronic address: frederic.bouillaud@inserm.fr.
Frédéric
F
Bouillaud
Inserm U1016, Institut Cochin, 75014 Paris Cedex, France; CNRS UMR 8104, 75014 Paris Cedex, France; Université Paris Descartes UMRS1016, 75014 Paris Cedex, France.
Marie-Clotilde
MC
Alves-Guerra
Inserm U1016, Institut Cochin, 75014 Paris Cedex, France; CNRS UMR 8104, 75014 Paris Cedex, France; Université Paris Descartes UMRS1016, 75014 Paris Cedex, France; Hôpital Necker-Enfants Malades AP-HP, Paris, France.
Daniel
D
Ricquier
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008322:Mammals / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051336:Mitochondrial Membranes / Q000378:metabolism; D000071245:Mitochondrial Uncoupling Proteins / Q000502:physiology*; D005810:Multigene Family; D009711:Nucleotides / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010539:Permeability; D011522:Protons; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D022722:Thermogenesis / Q000502:physiology
D005227:Fatty Acids; D000071245:Mitochondrial Uncoupling Proteins; D009711:Nucleotides; D011522:Protons; D029701:Saccharomyces cerevisiae Proteins
UCP; energy expenditure; ion transport; metabolism; mitochondria; reactive oxygen species