Lipid Droplet Nucleation

All living organisms can make lipid droplets (LDs), intracellular oil-in-water droplets, surrounded by a phospholipid and protein monolayer. LDs are at the nexus of cellular lipid metabolism and function in diverse biological processes. During the past decade, multidisciplinary approaches have shed light on LD assembly steps from the endoplasmic reticulum (ER): nucleation, growth, budding, and formation of a separate organelle. However, the molecular mechanisms underpinning these steps remain elusive. In this review, we focus on the nucleation step, defining where and how LD assembly is initiated. We present how membrane biophysical and physicochemical properties control this step and how proteins act on it to orchestrate LD biogenesis.