Cell Metab. 14, 504–515 (2011)

Credit: TOBIAS WALTHER

Lipid droplets (LD) store neutral sterol esters and triglyceride (TG) lipids in their cores, which are limited by a phospholipid monolayer. LD size fluctuates considerably in response to TG storage needs. More is known about how core lipids are generated during lipid flux than about how membrane phospholipids are generated, though knockdown of mammalian CCT enzymes that catalyze the rate-limiting step of phosphatidylcholine (PC) biosynthesis causes fusion of smaller LDs to form enlarged LDs. Krahmer et al. now confirm this result in Drosophila melanogaster cells and further show that the phenotype is reversed by addition of PC-containing liposomes. Through experiments using artificial LDs of different phospholipid compositions, the authors also found that PC acts as a surfactant that stabilizes LDs and prevents their coalescence and subsequent fusion. Among the PC biosynthetic enzymes, only CCT localized to LDs, suggesting that it has a regulatory purpose. Indeed, the authors show that when the amount of TG increases, the concentration of PC on LDs initially drops, leading to the targeting of CCT to the expanding LD surface, an event that activates this enzyme and thus increases PC synthesis. Once PC concentrations stabilize, CCT no longer binds to LDs and—owing to its nuclear localization sequence—trafficks to the nucleus. The results suggest that CCT regulation by LD binding is most likely part of a dynamic, homeostatic mechanism for PC synthesis.