Transport function and regulation of mitochondrial uncoupling proteins 2 and 3.
Uncoupling protein 1 (UCP1) dissipates energy and generates heat by catalyzing back-flux of protons into the mitochondrial matrix, probably by a fatty acid cycling mechanism. If the newly discovered UCP2 and UCP3 function similarly, they will enhance peripheral energy expenditure and are potential molecular targets for the treatment of obesity. We expressed UCP2 and UCP3 in Escherichia coli and reconstituted the detergent-extracted proteins into liposomes. Ion flux studies show that purified UCP2 and UCP3 behave identically to UCP1. They catalyze electrophoretic flux of protons and alkylsulfonates, and proton flux exhibits an obligatory requirement for fatty acids. Proton 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.
Jabůrek
M
M
Department of Biochemistry and Molecular Biology, Oregon Graduate Institute of Science and Technology, Beaverton, Oregon 97006-8921, USA.
Varecha
M
M
Gimeno
R E
RE
Dembski
M
M
Jezek
P
P
Zhang
M
M
Burn
P
P
Tartaglia
L A
LA
Garlid
K D
KD
D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels; D007700:Kinetics; D007850:Lauric Acids / Q000494:pharmacology; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011685:Purine Nucleotides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013050:Spectrometry, Fluorescence; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D007850:Lauric Acids; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D011685:Purine Nucleotides; D011994:Recombinant Proteins; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3