Recombinant human uncoupling protein-3 increases thermogenesis in yeast cells

The long form of human uncoupling protein-3 (hUCP3L) is highly homologous t o thermogenin (UCP1), the uncoupling protein of brown fat mitochondria, but is expressed predominantly in skeletal muscle. Its putative role is to reg ulate the coupling efficiency of oxidative phosphorylation and thus thermog enesis in skeletal muscle, a major thermogenic tissue in higher mammals. To study the functional relevance of hUCP3L, the protein was expressed in yea st cells under the control of the galactose promoter. Expression of hUCP3L induced a series of phenotype changes in the yeast cells. The cellular grow th and the mitochondrial membrane potential were both diminished. The porti on of cellular respiration coupled to oxidative phosphorylation decreased f rom 57% to 11% (P<0.001) and the cellular heat production, as measured by d irect microcalorimetry,,vas increased by 33.3 +/- 3.2% (P < 0.001) after in duction of UCP3L. These observations demonstrate for the first time the int rinsic thermogenic properties of hUCP3L in intact cells. (C) 1999 Federatio n of European Biochemical Societies.