Coordination of stress response signaling and phospholipid metabolism in yeast

Abstract

Previously we showed that the availability of the lipid precursor inositol influences the levels and rates of synthesis and turnover of inositol phospholipids, phosphoinositides and complex sphingolipids. To discover the inositol‐dependent mechanisms that lead to activation of lipid‐mediated signaling pathways, we compared the simultaneous changes in lipid metabolism with those occurring in gene expression in yeast cells during a 3‐hour period of inositol starvation followed by a 30‐min period of inositol add‐back. We found that inositol starvation and add‐back led to dramatic changes in the abundance of inositol‐containing phospholipids, including phosphatidylinositol, the phosphoinositides, and complex sphingolipids. These changes were accompanied by the altered expression of hundreds of genes involved in diverse stress response pathways. Significantly we found that many mutants deleted for nonessential genes in the same stress response pathways exhibit inositol auxotrophy. These results suggest that activation of stress response signaling pathways is coordinated with inositol‐containing phospholipid metabolism.