A unifying mechanism for seipin‐mediated lipid droplet formation

Abstract

Lipid droplets (LDs) are dynamic organelles essential for cellular lipid homeostasis. Assembly of LDs occurs in the endoplasmic reticulum (ER), and the conserved ER membrane protein seipin emerged as a key player in this process. Here, we review recent advances provided by structural, biochemical, and in silico analysis that revealed mechanistic insights into the molecular role of the seipin complexes and led to an updated model for LD biogenesis. We further discuss how other ER components cooperate with seipin during LD biogenesis. Understanding the molecular mechanisms underlying seipin‐mediated LD assembly is important to uncover the fundamental aspects of lipid homeostasis and organelle biogenesis and to provide hints on the pathogenesis of lipid storage disorders.

Zooming into lipid droplet biology through the lens of electron microscopy

“…Following neutral lipid synthesis within the ER leaflets, the lipodystrophy protein seipin is postulated to catalyze LD nucleation, a model suggested by the partial cryo-EM structures of seipin [131][132][133][134] and molecular dynamics simulations supported by cell biology experiments [135][136][137][138]. For a more detailed discussion on seipin and its structures, we point the reader to a thorough review included in this issue of FEBS letters [139]. Altogether, these recent works start to build a molecular view of LD assembly.…”