Properties of the human long and short isoforms of the uncoupling protein-3 expressed in yeast cells

Two splice variants of the human uncoupling protein-3 (UCP3L and UCP3S) are highly expressed in skeletal muscle. The properties of UCP3L and S have be en compared to those of UCP1 in a heterologous yeast expression system unde r the control of the galactose promoter. Both UCP3 isoforms were found to s trongly impair the coupling efficiency of respiring cells thus resulting in increased thermogenesis, The uncoupling properties of both UCP3L and S cou ld be clearly demonstrated also in isolated yeast mitochondria both in term s of coupled respiration and in the capacity to polarize the inner membrane in conditions of limited substrate availability. Contrary to what was obse rved with mitochondria containing UCP1, millimolar GDP and ATP had little i f any effect on the uncoupling activity of UCP3, A very marked uncoupling o f whole cells and isolated mitochondria was observed at very low expression levels of UCP3S indicating that the short isoform is more active than the long one. (C) 1999 Federation of European Biochemical Societies.