Mitochondrial uncoupling proteins: regulation and physiological role

Uncoupling proteins (UCPs), members of mitochondrial carrier family, are present in mitochondrial inner membrane and mediate free fatty acid-activated, purine-nucleotide-inhibited H+ re-uptake. UCPs can modulate the tightness of coupling between mitochondrial respiration and ATP synthesis. A physiological function of the first described UCP, UCP1 or termogenin, present in mitochondria of mammalian brown adipose tissues is well established. UCP1 plays a role in nonshivering thermogenesis in mammals. The widespread presence of UCPs in eukaryotes, in non-thermogenic tissues of animals, plants and in unicellular organisms implies that these proteins may elicit other functions than thermogenesis. However, the physiological functions of UCP1 homologues are still under debate. They can regulate energy metabolism through modulation of the electrochemical proton gradient and production of ROS. Functional activation of UCPs is proposed to decrease ROS production. Moreover, products of lipid peroxidation can activate UCPs and promote feedback down-regulation of mitochondrial ROS production.