GPI lipid remodeling regulates lipophagy in response to glucose deprivation

Lipophagy is an important microautophagic process that degrades lipid droplets (LDs) to mobilize stored lipids as an energy source during nutrient starvation. However, the molecular mechanisms regulating lipophagy in response to nutrient starvation remain poorly understood. We found that budding yeast mutants defective in glycosylphosphatidylinositol (GPI) lipid remodeling exhibited aberrant accumulation of lipid droplets (LDs), neutral lipids, and a reduced degradation of Faa4-GFP, a lipophagy reporter under glucose starvation. Furthermore, we demonstrated that glycosylphosphatidylinositol-anchored proteins (GPI-APs) localize to vacuoles in response to glucose depletion, and that a mutant defective in endocytosis has defects in lipophagy. These results imply that GPI lipid remodeling is required for lipophagy upon glucose starvation, and we propose that endocytosis functions to supply the lipid portion of GPI-APs, remodeled to C26 diacylglycerol, to the vacuolar membrane for lipophagy.