Epistatic interactions of deletion mutants in the genes encoding the F1-ATPase in yeast Saccharomyces cerevisiae

The F-1-ATPase is a multimeric enzyme (alpha(3)beta(3)gamma delta epsilon) primarily responsible for the synthesis of ATP under aerobic conditions. The entire coding region of each of the genes was deleted separately in yeast, providing five null mutant strains. Strains with a deletion in the genes encoding alpha-, beta-, gamma- or delta-subunits were unable to grow while the strain with a null mutation in epsilon was able to grow slowly on medium containing glycerol as the carbon source, In addition, strains with a null mutation in gamma or delta became 100% rho(0)/rho(-) and the strain with the null mutation in gamma grew much more slowly on medium containing glucose. These additional phenotypes were not observed in strains with the double mutations: Delta alpha Delta gamma, Delta beta Delta gamma, Delta atp11 Delta gamma, Delta alpha Delta delta, Delta beta Delta delta or Delta atp11 Delta delta. These results indicate that epsilon is not an essential component of the ATP synthase and that mutations in the genes encoding the alpha- and beta-subunits and in ATP11 are epistatic to null mutations in the genes encoding the gamma- and delta-subunits, These data suggest that the propensity to form rho(0)/rho(-) mutations in the gamma and delta null deletion mutant stains and the slow growing phenotypes of the null gamma mutant strain are due to the assembly of F-1 deficient in the corresponding subunit. These results have profound implications for the physiology of normal cells.