Uncoupling Proteins

Abstract

Uncoupling proteins (UCPs) are mitochondrial transporters present in the inner membrane of mitochondria. They belong to the family of anion mitochondrial carriers including adenine nucleotide transporters, phosphate carrier, and other transporters. The term ‘uncoupling protein’ was originally given to UCP1 which is uniquely present in mitochondria of brown adipocytes, the thermogenic cells devoted to maintenance of body temperature in mammals. In these cells, UCP1 acts as a proton carrier creating a shunt between complexes of respiratory chain and the adenosine triphosphate-synthase. Purine nucleotide inhibits UCP1, whereas fatty acids activate it. Activation of UCP1 stimulates respiration and the uncoupling process results in a futile cycle and dissipation of oxidation energy into heat. UCP2 is ubiquitous and highly expressed in lymphoid system and macrophages and also in gut, lung, and brain. UCP3 is mainly expressed in skeletal muscles. In comparison to the established uncoupling and thermogenic activities of UCP1, UCP2, and UCP3 rather appear to be involved in the limitation of free radicals levels in cells than in physiological uncoupling and thermogenesis. These novel UCPs are also involved in sparing glucose utilization and consequently in the control of fatty acids and glutamine metabolism. The mechanism of the protonophoric activity of UCP1 is still controversial since it has been proposed that UCP1 transports fatty acid anions and catalyzes proton transport by fatty acid cycling. Quinones and superoxide ions may also activate the UCPs.