美国弗吉尼亚大学Ilya Levental研究小组发现了细胞膜通过胆固醇不对称维持磷脂不平衡。相关论文于2025年4月2日发表在《细胞》杂志上。

该课题组研究人员证明这种假设通常是无效的，并研究了哺乳动物质膜（PMs）中脂质丰度失衡的后果。利用脂质组学，课题组报道了人红细胞膜细胞质小叶的磷脂比外质小叶多50%。这种不平衡是由胆固醇的不对称叶间分布引起的，这调节了细胞胆固醇的稳态。这些特征产生了独特的功能特征，包括低PM渗透率和调节蛋白质定位的细胞质小叶的静息张力。

据介绍，细胞膜是分子界面，它将细胞分隔开来，以控制营养物质和信息的流动。这些功能是由不同的脂质集合促进的，几乎所有的脂质都不对称地分布在两个双层小叶之间。大多数生物膜结构和功能模型都隐含假设这些小叶具有相似的磷脂丰度。

附：英文原文

Title: Cell membranes sustain phospholipid imbalance via cholesterol asymmetry

Author: Milka Doktorova, Jessica L. Symons, Xiaoxuan Zhang, Hong-Yin Wang, Jan Schlegel, Joseph H. Lorent, Frederick A. Heberle, Erdinc Sezgin, Edward Lyman, Kandice R. Levental, Ilya Levental

Issue&Volume: 2025-04-02

Abstract: Membranes are molecular interfaces that compartmentalize cells to control the flow of nutrients and information. These functions are facilitated by diverse collections of lipids, nearly all of which are distributed asymmetrically between the two bilayer leaflets. Most models of biomembrane structure and function include the implicit assumption that these leaflets have similar abundances of phospholipids. Here, we show that this assumption is generally invalid and investigate the consequences of lipid abundance imbalances in mammalian plasma membranes (PMs). Using lipidomics, we report that cytoplasmic leaflets of human erythrocyte membranes have >50% overabundance of phospholipids compared with exoplasmic leaflets. This imbalance is enabled by an asymmetric interleaflet distribution of cholesterol, which regulates cellular cholesterol homeostasis. These features produce unique functional characteristics, including low PM permeability and resting tension in the cytoplasmic leaflet that regulates protein localization.

DOI: 10.1016/j.cell.2025.02.034

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00270-3