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.
摘要:
脂滴(LD)是细胞脂质稳态所必需的动态细胞器。LD的组装发生在内质网(ER),保守的内质网膜蛋白seipin在这一过程中发挥了关键作用。这里,我们回顾了结构方面的最新进展,生物化学,和计算机模拟分析揭示了对seipin复合物的分子作用的机理见解,并导致了LD生物发生的更新模型。我们进一步讨论了在LD生物发生过程中其他ER成分如何与seipin合作。了解seipin介导的LD组装的分子机制对于揭示脂质稳态和细胞器生物发生的基本方面以及提供脂质贮积症发病机理的提示很重要。