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.