Lipid remodelling enables adaptation to chronic hyperosmotic stress

Abstract Lipid droplets (LDs) accumulate in response to diverse cellular stresses. However, their regulation and physiological roles remain poorly understood in most contexts. Here, we show that, in budding yeast, chronic hyperosmotic stress induces sustained LD accumulation. Unlike the transient LD response observed during acute osmotic shock, chronic stress triggers prolonged, Dga1-dependent triacylglycerol synthesis. In the absence of triacylglycerol synthesis cellular fitness is severely affected. Lipidomic profiling reveals extensive membrane remodelling during chronic hyperosmotic stress, most notably a shift from phosphatidylethanolamine to phosphatidylcholine. In LD-deficient cells, the stress–induced PC increase is blunted and manipulation of PC synthesis modulates the fitness of triacylglycerol-deficient cells under hyperosmotic stress. Thus, LD accumulation and phospholipid remodelling underlie an adaptive response to chronic hyperosmotic stress. Summary This work demonstrates that membrane remodelling occurs in cells experiencing chronic hyperosmotic stress. Both triacylglycerol and phosphatidylcholine levels are increased. Cell fitness depends upon increased triacylglycerol synthesis and is further modulated by manipulating phosphatidylcholine levels.