Borst Pauwels Shalom, Neefjes Jacques, Cabukusta Birol
Cell and Chemical Biology, ONCODE Institute, Leiden University Medical Center, 2333ZA Leiden, Netherlands.
J Cell Sci. 2025 Aug 1;138(15). doi: 10.1242/jcs.263971. Epub 2025 Aug 8.
The unique lipid composition of organelles defines their identity and is fundamental to their function. Lipid transfer proteins perform non-vesicular trafficking of lipids among cellular membranes to maintain their lipid compositions. Lipid transfer protein-mediated lipid trafficking is also essential for creating sub-organellar nano-domains that can recruit functional proteins or change the biophysical properties of membranes. The latest research focusing on the homo- and hetero-dimerization of lipid transfer proteins highlights the functional implications and the clinical significance of these events. Dimerization promotes lipid transfer protein localization at membrane contact sites and mediates the assembly of lipid transfer protein super-complexes to synchronize the transfer of different lipid types between organelles. Meanwhile, abnormal lipid flows caused by disarrangements in lipid transfer protein dimerization disturb organelle lipid landscapes, which has clinical consequences. This Review discusses the latest developments regarding the dimerization of lipid transfer proteins and their adaptor proteins that are critical for lipid trafficking between the organelles of the cell.
细胞器独特的脂质组成决定了它们的特性,并且对其功能至关重要。脂质转运蛋白在细胞膜之间进行脂质的非囊泡运输,以维持它们的脂质组成。脂质转运蛋白介导的脂质运输对于形成能够招募功能蛋白或改变膜生物物理特性的亚细胞器纳米结构域也是必不可少的。聚焦于脂质转运蛋白同二聚化和异二聚化的最新研究突出了这些事件的功能意义和临床重要性。二聚化促进脂质转运蛋白定位于膜接触位点,并介导脂质转运蛋白超复合物的组装,以同步细胞器之间不同脂质类型的转运。同时,脂质转运蛋白二聚化紊乱导致的异常脂质流动扰乱了细胞器脂质格局,从而产生临床后果。本综述讨论了脂质转运蛋白及其衔接蛋白二聚化的最新进展,这些进展对于细胞内细胞器之间的脂质运输至关重要。