Fission yeast Vps1 and Atg8 contribute to oxidative stress resistance
Fission yeast Vps1 and Atg8 contribute to oxidative stress resistance
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DOI：
10.1111/j.1365-2443.2009.01376.x
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发表时间：
2010-03-01
期刊：
影响因子：
2.1
通讯作者：
Ishikawa, Fuyuki
中科院分区：
文献类型：
--
作者：
Mikawa, Takumi;Kanoh, Junko;Ishikawa, Fuyuki
生物体已经进化出多种手段来保护自己免受氧化应激。为了更好地了解参与抗氧化应激的分子机制，我们筛选了对百草枯敏感的裂殖酵母突变体，百草枯是一种作用于线粒体产生活性氧的试剂。在我们分离的突变体中，我们集中在编码动力蛋白相关蛋白家族成员的vps 1+（液泡蛋白分选1）基因缺陷的突变体上。vps 1 δ在百草枯处理后表现出异常的线粒体和空泡形态。vps 1 δ对渗透胁迫、高浓度Ca ~（2+）和Fe ~（2+）敏感。有趣的是，atg 8+（一种自噬途径所必需的基因）的缺失与vps 1 delta表现出强烈的遗传相互作用。vps 1 delta atg 8 delta双突变体对氧化胁迫、渗透胁迫和Ca 2+的反应是加性的。vps 1+的缺失拯救了atg 8 δ所示的奇异的空泡形态。在其他atg突变体中没有观察到这种遗传相互作用。此外，atg 8-G116 A突变体在对氮饥饿（一种自噬相关表型）敏感的同时，没有表现出异常的液泡形态。综上所述，我们得出结论atg 8+调节空泡功能独立的自噬作用。我们建议，Vps 1和Atg 8合作参与液泡功能，从而有助于抗氧化应激。
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. vps1 delta exhibited aberrant mitochondrial and vacuolar morphology on treatment with paraquat. vps1 delta was sensitive to osmotic stress, high concentrations of Ca2+ and Fe2+. Interestingly, the deletion of atg8+, a gene essential for the autophagy pathway, exhibited strong genetic interactions with vps1 delta. The vps1 delta atg8 delta double mutant was additively sensitive to oxidative stress, osmotic stress and Ca2+. The deletion of vps1+ rescued the bizarre vacuolar morphology shown by atg8 delta. 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.