title: 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.
authors.affiliation: Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Mikawa
authors.forename: Junko
authors.initials: J
authors.lastname: Kanoh
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Ishikawa
mesh_terms: 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*
chemical_list: 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