The Role of Fatty Acids in the Activity of the Uncoupling Proteins

The uncoupling proteins (UCPs) are mitochondrial transporters that, according to their family name, should lower the efficiency of the oxidative phosphorylation. The uncoupling protein from brown adipose tissue UCP1 is the best characterized member of the family. It is a proton carrier, activated by low fatty acid concentrations, that has a thermogenic function. The physiological role of the uncoupling protein UCP2 is probably related to control of the production of reactive oxygen species since it is upregulated in situations of oxidative stress. This uncoupling activity would explain a higher respiratory activity to minimize the generation of superoxide or the modulation of the ATP levels in β-cells to control insulin secretion. The activity of UCP3 appears linked to lipid metabolism in muscle. The role could also be as a defence against oxidative stress although it has also been hypothesized to prevent fatty acid accumulation inside mitochondria. Fatty acids, when present at high concentrations, are known to interact with UCP2 and UCP3 but also with other mitochondrial carriers and therefore the specificity of those interactions is under debate. In this article we review our current understanding of the mechanism of transport, regulation and function of the mammalian uncoupling proteins.