Department of Molecular Biology and Genetics, Aarhus University, Denmark.
FEBS Lett. 2022 Jan;596(2):160-179. doi: 10.1002/1873-3468.14253. Epub 2021 Dec 20.
Sterols are an essential component of membranes in all eukaryotic cells and the precursor of multiple indispensable cellular metabolites. After endocytotic uptake, sterols are integrated into the lysosomal membrane by the Niemann-Pick type C (NPC) system before redistribution to other membranes. The process is driven by two proteins that, together, compose the NPC system: the lysosomal sterol shuttle protein NPC2 and the membrane protein NPC1 (named NCR1 in fungi), which integrates sterols into the lysosomal membrane. The Saccharomyces cerevisiae NPC system provides a compelling model to study the molecular mechanism of sterol integration into membranes and sterol homeostasis. This review summarizes recent advances in the field, and by interpreting available structural data, we propose a unifying conceptual model for sterol loading, transfer and transport by NPC proteins.
甾醇是所有真核细胞的膜的重要组成部分，也是多种必不可少的细胞代谢物的前体。在胞吞作用摄取后，甾醇通过尼曼-匹克 C 型（NPC）系统整合到溶酶体膜中，然后再分配到其他膜上。这个过程由两种蛋白驱动，它们共同构成 NPC 系统：溶酶体甾醇穿梭蛋白 NPC2 和膜蛋白 NPC1（在真菌中称为 NCR1），将甾醇整合到溶酶体膜中。酿酒酵母 NPC 系统为研究甾醇整合到膜中和甾醇动态平衡的分子机制提供了一个引人注目的模型。本综述总结了该领域的最新进展，并通过解释现有结构数据，我们提出了 NPC 蛋白加载、转移和运输甾醇的统一概念模型。
