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 alpha, beta and gamma subunit genes of F1-ATPase can suppress lethality due to loss of the mitochondrial genome from the petite-negative yeast Kluyveromyceslactis. 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, deltapsi, by enhanced export of protons through F1F0-ATP synthase connected to increased ATP hydrolysis at low substrate concentration.