alpha and beta subunits of F-1-ATPase are required for survival of petite mutants in Saccharomyces cerevisiae

Although Saccharomyces,ces cerevisiae can form petite mutants with deletion s in mitochondrial DNA (mtDNA) (p(-)) and can survive complete loss of the gaanellar genome (p(o)), the genetic factor(s) that permit(s) survival of p (-) and p(o) mutants remain(s) unknown. In this report we show that a funct ion associated with the F-1-ATPase, which is distinct from its role in ener gy transduction, is required for the petite-positive phenotype of S. cerevi siae. Inactivation of either the alpha or beta subunit, but not the gamma, delta, or epsilon subunit of F-1, renders cells petite-negative. The F-1 co mplex, or a subcomplex composed of the alpha and beta subunits only, is ess ential for survival of p(o) cells and those impaired in electron transport. The activity of F1 that suppresses p(o) lethality is independent of the me mbrane F-o complex, but is associated with an intrinsic ATPase activity. A further demonstration of the ability of F-1 subunits to suppress p(o) letha lity has been achieved by simultaneous expression of S. cerevisiae F-1 alph a and gamma subunit genes in Kluyveromyces lactis - which allows this petit e-negative yeast to survive the loss of its mtDNA. Consequently, ATP1 and A TP2, in addition to the previously identified AAC2, YME1 and PELI/PGSI gene s, are required for establishment of p(-) or p(o) mutations in S. cerevisia e.