Protective role of the HOG pathway against the growth defect caused by impaired biosynthesis of complex sphingolipids in yeast Saccharomyces cerevisiae

• Published in: Molecular microbiology Vol. 107; no. 3; pp. 363 - 386
• Main Authors: Yamaguchi, Yutaro, Katsuki, Yuka, Tanaka, Seiya, Kawaguchi, Ryotaro, Denda, Hiroto, Ikeda, Takuma, Funato, Kouichi, Tani, Motohiro
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.02.2018
• Subjects: Aberration; Baking yeast; Basic-Leucine Zipper Transcription Factors - metabolism; Biosynthesis; Cell growth; Ceramide; Ceramides - metabolism; Defects; DNA-Binding Proteins - metabolism; Gene Deletion; Gene regulation; Genes; Genetic suppression; Glycerol; Glycerol - metabolism; Glycosphingolipids - metabolism; Hexosyltransferases - genetics; Hexosyltransferases - metabolism; Hexosyltransferases - physiology; Inositol; Mutation; Osmolar Concentration; Osmolarity; Reactive oxygen species; Repressor Proteins - metabolism; Restoration; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Sphingolipids; Sphingolipids - biosynthesis; Sphingolipids - metabolism; Transcription activation; Transcription Factors - metabolism; Yeast
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.13886

Summary Complex sphingolipids play critical roles in various cellular events in the yeast Saccharomyces cerevisiae. To identify genes that are related to the growth defect caused by disruption of complex sphingolipid biosynthesis, we screened for suppressor mutations and multicopy suppressor genes that confer resistance against repression of AUR1 encoding inositol phosphorylceramide synthase. From the results of this screening, we found that the activation of high‐osmolarity glycerol (HOG) pathway is involved in suppression of growth defect caused by impaired biosynthesis of complex sphingolipids. Furthermore, it was found that transcriptional regulation via Msn2, Msn4 and Sko1 is involved in the suppressive effect of the HOG pathway. Lack of the HOG pathway did not enhance the reductions in complex sphingolipid levels or the increase in ceramide level caused by the AUR1 repression, implying that the suppressive effect of the HOG pathway on the growth defect is not attributed to restoration of impaired biosynthesis of complex sphingolipids. On the contrary, the HOG pathway and Msn2/4‐mediated transcriptional activation was involved in suppression of aberrant reactive oxygen species accumulation caused by the AUR1 repression. These results indicated that the HOG pathway plays pivotal roles in maintaining cell growth under impaired biosynthesis of complex sphingolipids. Complex sphingolipids are one of the major components of the biomembranes of eukaryotic organisms, and are essential for normal cell growth of the yeast Saccharomyces cerevisiae. We found that the activation of high‐osmolarity glycerol (HOG) pathway plays pivotal roles in maintaining cell growth under impaired biosynthesis of complex sphingolipids.