Mitochondrial uncoupling proteins in eukaryotic world

Uncoupling proteins (UCPs) are members of the anion carrier protein family that are present in the mitochondrial inner membrane and mediate a proton conductance dissipating the mitochondrial electrochemical proton gradient. A physiological function of the first described UCP, UCP1 or termogenin, present in mitochondria of mammalian brown adipose tissue is participation in nonshivering thermogenesis. The widespread presence of UCPs in eukaryotes, in non-thermogenic tissues of animals (mammals, birds, fish, insects), plants and in unicellular organisms implies that these proteins may have functions other than thermogenesis. They can regulate energy metabolism through modulation of the tightness of coupling between mitochondrial respiration and ATP synthesis and modulation of reactive oxygen species (ROS) production (a preventive action). Moreover, products of lipid peroxidation can activate UCPs and promote a feedback down-regulation of mitochondrial ROS production. UCPs seem to be new targets for pharmacological management of complex pathological syndromes such as obesity, type 2 diabetes or chronic inflammatory diseases. UCP activity is revealed upon free fatty acid-induced, purine nucleotide-inhibited stimulation of resting respiration and a decrease in membrane potential, which are accompanied by a decrease in membranous ubiquinone (Q) reduction level. Our recent work indicates that membranous Q is a metabolic sensor that might utilise its redox state to release the purine nucleotide-inhibition of UCP-mediated mitochondrial uncoupling under conditions of phosphorylation and resting respiration. The action of reduced Q (QH2) could allow higher or complete activation of UCP. As this regulatory feature was demonstrated for microorganism UCPs (A. castellanii UCP), plant and mammalian UCP1 analogues, and UCP1 in brown adipose tissue, the process could involve all UCPs. L8.2