Transport function and regulation of mitochondrial uncoupling proteins 2 and 3

Uncoupling protein 1 (UCP1) dissipates energy and generates heat by catalyz ing back-flux of protons into the mitochondrial matrix, probably by a fatty acid cycling mechanism. If the newly discovered UCP2 and UCP3 function sim ilarly, they will enhance peripheral energy expenditure and are potential m olecular targets for the treatment of obesity. We expressed UCP2 and UCP3 i n Escherichia coli and reconstituted the detergent-extracted proteins into liposomes, Ion flux studies show that purified UCP2 and UCP3 behave identic ally to UCP1, They catalyze electrophoretic flux of protons and alkylsulfon ates, and proton flux exhibits an obligatory requirement for fatty acids. P roton flux is inhibited by purine nucleotides but with much lower affinity than observed with UCP1, These findings are consistent with the hypothesis that UCP2 and UCP3 behave as uncoupling proteins in the cell.