Prof. Sabrina Büttner, University of Münster

Lipid droplets (LDs) are fat-storage organelles critical for energy and lipid metabolism. When nutrients are depleted, cells break down LDs through gradual cytosolic lipolysis or through lipophagy, the en bloc uptake of LDs into the lysosomal or vacuolar compartments. We have shown that LDs dock to the vacuolar membrane via a previously unexplored membrane contact site that is required for lipophagy in yeast. The LD-localized LDO proteins contain an intrinsically disordered region that directly binds to the vacuolar protein Vac8 to form vCLIP, the vacuole-lipid droplet contact site. Nutrient limitation drives vCLIP formation, and genetic inactivation of vCLIP blocks lipophagy, resulting in impaired longevity induced by caloric restriction. While the identification of vCLIP provides mechanistic insights into the docking of LDs to the vacuolar surface—a process required for subsequent lipophagic LD engulfment—it remains unknown how LDs are degraded inside the vacuole. Our recent data suggest a model for vacuolar LD consumption in which cytosolic lipases are delivered to the vacuole during lipophagy at specific LD-associated foci and facilitate the degradation of LDs inside microautophagic vesicles within the vacuolar lumen.