Kinetic properties of F₁-ATPase influence the ability of yeasts to grow in anoxia or absence of mtDNA

A mechanism for hypoxia survival by eukaryotic cells is suggested from studies on the petite mutation of yeasts. Previous work has shown that mutations in the α, β and γ subunit genes of F₁-ATPase can suppress lethality due to loss of the mitochondrial genome from the petite-negative yeast Kluyveromyces lactis. Here it is reported that suppressor mutations appear to increase the affinity of F₁-ATPase for ATP. Extension of this study to other yeasts shows that petite-positive species have a higher affinity for ATP in the hydrolysis reaction than petite-negative species. Possession of a F₁-ATPase with a low K _m for ATP is considered to be an adaptation for hypoxic growth, enabling maintenance of the mitochondrial inner membrane potential, ΔΨ, by enhanced export of protons through F₁F₀-ATPsynthase connected to increased ATP hydrolysis at low substrate concentration.