Retromer Complex and PI3K Complex II-Related Genes Mediate the Yeast (Saccharomyces cerevisiae) Sodium Metabisulfite Resistance Response.
Retromer Complex and PI3K Complex II-Related Genes Mediate the Yeast (Saccharomyces cerevisiae) Sodium Metabisulfite Resistance Response.
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作者：
Jin X;Zhao H;Zhou M;Zhang J;An T;Fu W;Li D;Cao X;Liu B
焦亚硫酸钠 (Na2S2O5) 广泛用作食品和葡萄酒行业的防腐剂。然而，它会对生物体造成不同程度的细胞损伤。为了提高我们对其细胞毒性的了解，使用酵母单缺失集合进行了全基因组筛选。此外，共鉴定出 162 株 Na2S2O5 敏感菌株和 16 株 Na2S2O5 耐受菌株。在 162 个 Na2S2O5 耐受相关基因中，retromer 复合体是最富集的细胞成分。进一步分析表明，retromer复合物缺失导致对Na2S2O5的敏感性增加，并且Na2S2O5可以诱导retromer复合物蛋白的错误定位。值得注意的是，磷脂酰肌醇 3-单磷酸激酶 (PI3K) 复合物 II 对于逆转录酶招募到内体很重要，可能是介导逆转录酶定位和酵母 Na2S2O5 耐受反应的潜在调节因子。 Na2S2O5 可以降低 Vps34 的蛋白表达，Vps34 是 PI3K 复合物的组成部分。因此，Na2S2O5 介导的逆转录酶重新分布可能是由 Vps34 表达水平降低的影响引起的。此外，Vps34 功能的药物抑制和 PI3K 复合物 II 相关基因的缺失都会影响细胞对 Na2S2O5 的耐受性。我们的研究结果提供了 Na2S2O5 耐受性所需的细胞成分的整体情况，并加深了我们对 Na2S2O5 诱导的细胞毒性作用的理解。
Sodium metabisulfite (Na2S2O5) is widely used as a preservative in the food and wine industry. However, it causes varying degrees of cellular damage to organisms. In order to improve our knowledge regarding its cyto-toxicity, a genome-wide screen using the yeast single deletion collection was performed. Additionally, a total of 162 Na2S2O5-sensitive strains and 16 Na2S2O5-tolerant strains were identified. Among the 162 Na2S2O5 tolerance-related genes, the retromer complex was the top enriched cellular component. Further analysis demonstrated that retromer complex deletion leads to increased sensitivity to Na2S2O5, and that Na2S2O5 can induce mislocalization of retromer complex proteins. Notably, phosphatidylinositol 3-monophosphate kinase (PI3K) complex II, which is important for retromer recruitment to the endosome, might be a potential regulator mediating retromer localization and the yeast Na2S2O5 tolerance response. Na2S2O5 can decrease the protein expressions of Vps34, which is the component of PI3K complex. Therefore, Na2S2O5-mediated retromer redistribution might be caused by the effects of decreased Vps34 expression levels. Moreover, both pharmaceutical inhibition of Vps34 functions and deletions of PI3K complex II-related genes affect cell tolerance to Na2S2O5. The results of our study provide a global picture of cellular components required for Na2S2O5 tolerance and advance our understanding concerning Na2S2O5-induced cytotoxicity effects.
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