Retromer Complex and PI3K Complex II-Related Genes Mediate the Yeast (Saccharomyces cerevisiae) Sodium Metabisulfite Resistance Response

Sodium metabisulfite (Na(2)S(2)O(5)) 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 Na(2)S(2)O(5)-sensitive strains and 16 Na(2)S(2)O(5)-tolerant strains were identified. Among the 162 Na(2)S(2)O(5) tolerance-related genes, the retromer complex was the top enriched cellular component. Further analysis demonstrated that retromer complex deletion leads to increased sensitivity to Na(2)S(2)O(5), and that Na(2)S(2)O(5) 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 Na(2)S(2)O(5) tolerance response. Na(2)S(2)O(5) can decrease the protein expressions of Vps34, which is the component of PI3K complex. Therefore, Na(2)S(2)O(5)-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 Na(2)S(2)O(5). The results of our study provide a global picture of cellular components required for Na(2)S(2)O(5) tolerance and advance our understanding concerning Na(2)S(2)O(5)-induced cytotoxicity effects.