From the biophysics to the cell biology of lipid droplets

Lipid droplets are central hubs in cellular energy metabolism and play roles in diverse non-metabolic processes such as infection, senescence, and cancer. Structurally, lipid droplets consist of a neutral lipid core—primarily triglycerides—encased by a phospholipid monolayer embedded with various proteins. Lipid droplet biogenesis occurs at the endoplasmic reticulum (ER) through a phase separation mechanism, followed by droplet growth and budding. Throughout these stages, proteins dynamically relocate from the ER to the LD surface, dictating the biological functions of the droplets. Despite significant progress in recent years, critical gaps remain in our understanding of the molecular mechanisms driving lipid droplet nucleation and functionalization by proteins. This challenge stems partly from the difficulty in accurately reproducing and dissecting the steps of lipid droplets’ formation and protein targeting. In my talk, I will present our recent findings, offering new insights into the biogenesis of lipid droplets and the mechanisms by which they recruit proteins.