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

Valeria Zoni, Rasha Khaddaj, Ivan Lukmantara, Wataru Shinoda, Hongyuan Yang, Roger Schneiter, Stefano Vanni

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere2017205118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number10
DOIs
Publication statusPublished - Mar 9 2021
Externally publishedYes

Keywords

  • Endoplasmic reticulum
  • Lipid droplets
  • Lipid membranes
  • Molecular dynamics
  • Seipin

ASJC Scopus subject areas

  • General

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