Lipid remodeling enables adaptation to chronic hyperosmotic stress.

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 impaired. Lipidomic profiling reveals extensive membrane remodeling during chronic hyperosmotic stress, most notably an increase in phosphatidylcholine (PC) resulting in changes to membrane properties. In LD-deficient cells, the hyperosmotic stress-induced PC increase is blunted, while enhancing PC synthesis improves the fitness of triacylglycerol-deficient cells. Thus, LD accumulation and phospholipid remodeling underlie an adaptive response to chronic hyperosmotic stress.