Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure

Lipid droplets (LDs) are intracellular organelles responsible for lipid storage, and they emerge from the endoplasmic reticulum (ER) upon the accumulation of neutral lipids, mostly triglycerides (TG), between the two leaflets of the ER membrane. LD biogenesis takes place at ER sites that are marked by the protein seipin, which subsequently recruits additional proteins to catalyze LD formation. Deletion of seipin, however, does not abolish LD biogenesis, and its precise role in controlling LD assembly remains unclear. Here, we use molecular dynamics simulations to investigate the molecular mechanism through which seipin promotes LD formation. We find that seipin clusters TG, as well as its precursor diacylglycerol, inside its unconventional ring-like oligomeric structure and that both its luminal and transmembrane regions contribute to this process. This mechanism is abolished upon mutations of polar residues involved in protein-TG interactions into hydrophobic residues. Our results suggest that seipin remodels the membrane of specific ER sites to prime them for LD biogenesis.

Automated summary

Lipid droplets are intracellular organelles responsible for lipid storage that emerge from the endoplasmic reticulum. Through molecular dynamics simulations, it has been revealed that seipin promotes lipid droplet formation by clustering lipids in its unconventional ring-like oligomeric structure, suggesting a role in priming specific ER sites for LD biogenesis.