Partial uncoupling of the mitochondrial membrane by a heterozygous null mutation in the gene encoding the gamma- or delta-subunit of the yeast mitochondrial ATPase

Prior genetic studies indicated that the yeast mitochondrial ATP synthase c an be assembled into enzyme complexes devoid of the gamma-, delta-, or epsi lon-subunits (Lai-Zhang, J., Xiao, Y., and Mueller, D, M. (1999) EMBO J, 18 , 58-64), These subunit-deficient complexes were postulated to uncouple the mitochondrial membrane thereby causing negative cellular phenotypes, This study provides bio chemical and additional genetic data that support this h ypothesis. The genetic data indicate that in a diploid cell, a heterozygous deletion mutation in the gene encoding the gamma- or delta-subunit of the ATPase is semidominant negative due to a decrease in the gene number from 2 to 1, However, the heterozygous atp2 Delta mutation is epistatic to the he terozygous mutation in the gene encoding gamma or delta, suggesting that th e semidominant negative effect is because of a gain of activity in the cell s. Biochemical studies using mitochondria isolated from the yeast strains t hat are heterozygous for a mutation in gamma or delta indicate that the mit ochondria are partially uncoupled. These results support the hypothesis tha t the negative phenotypes are caused by the formation of a gamma- or delta- less ATP synthase complex that is uncoupled.