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.

• PMID: 34944020
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Jin X, Zhao H, Zhou M, Zhang J, An T, Fu W, Li D, Cao X, Liu B

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