Fission yeast Vps1 and Atg8 contribute to oxidative stress resistance.
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.
Mikawa
Takumi
T
Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Kanoh
Junko
J
Ishikawa
Fuyuki
F
D001343:Autophagy / Q000235:genetics; D000071190:Autophagy-Related Protein 8 Family; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D009997:Osmotic Pressure; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D000071190:Autophagy-Related Protein 8 Family; D029702:Schizosaccharomyces pombe Proteins; C000598240:autophagy associated protein Atg8, S pombe; D013481:Superoxides; C548065:Vps1 protein, S pombe; D020691:rab GTP-Binding Proteins; D010269:Paraquat