Fission yeast Vps1 and Atg8 contribute to oxidative stress resistance

Abstract

Organisms have evolved diverse means to protect themselves from oxidative stress. To better understand the molecular mechanisms involved in oxidative stress resistance, we screened fission yeast mutants sensitive to paraquat, a reagent acting on the mitochondria to generate reactive oxygen species. Among the mutants we isolated, we focused on a mutant defective in the vps1(+) (vacuolar protein sorting 1) gene that encodes a dynamin-related protein family member. vps1Δ exhibited aberrant mitochondrial and vacuolar morphology on treatment with paraquat. vps1Δ was sensitive to osmotic stress, high concentrations of Ca(2+) and Fe(2+). Interestingly, the deletion of atg8(+), a gene essential for the autophagy pathway, exhibited strong genetic interactions with vps1Δ. The vps1Δatg8Δ double mutant was additively sensitive to oxidative stress, osmotic stress and Ca(2+). The deletion of vps1(+) rescued the bizarre vacuolar morphology shown by atg8Δ. Such genetic interactions were not observed with other atg mutants. Furthermore, the atg8-G116A mutant did not show abnormal vacuolar morphology while being sensitive to nitrogen starvation, an autophagy-related phenotype. Taken together, we conclude that atg8(+) regulates vacuolar functions independently of its role in autophagy. We propose that Vps1 and Atg8 cooperatively participate in vacuolar function, thereby contributing to oxidative stress resistance.