All living organisms can make lipid droplets (LDs), intracellular oil-in-water droplets, surrounded by a phospholipid and protein monolayer. LDs are at the nexus of cellular lipid metabolism and function in diverse biological processes. During the past decade, multidisciplinary approaches have shed light on LD assembly steps from the endoplasmic reticulum (ER): nucleation, growth, budding, and formation of a separate organelle. However, the molecular mechanisms underpinning these steps remain elusive. In this review, we focus on the nucleation step, defining where and how LD assembly is initiated. We present how membrane biophysical and physicochemical properties control this step and how proteins act on it to orchestrate LD biogenesis.

所有活的生物体都可以产生脂滴 (LD)，即细胞内的水包油滴，被磷脂和蛋白质单层包围。LDs 是细胞脂质代谢的纽带，并在不同的生物过程中发挥作用。在过去的十年中，多学科方法揭示了内质网 (ER) 的 LD 组装步骤：成核、生长、出芽和单独细胞器的形成。然而，支撑这些步骤的分子机制仍然难以捉摸。在这篇综述中，我们关注成核步骤，定义了 LD 组装的起始位置和方式。我们介绍了膜生物物理和物理化学特性如何控制这一步，以及蛋白质如何作用于它以协调 LD 生物发生。