Center for Quality Management Systems, National Institute of Infectious Diseases, Tokyo, Japan.
Bioessays. 2024 Aug;46(8):e2400045. doi: 10.1002/bies.202400045. Epub 2024 Jun 27.
Various lipid transfer proteins (LTPs) mediate the inter-organelle transport of lipids. By working at membrane contact zones between donor and acceptor organelles, LTPs achieve rapid and accurate inter-organelle transfer of lipids. This article will describe the emerging paradigm that the action of LTPs at organelle contact zones generates metabolic channeling events in lipid metabolism, mainly referring to how ceramide synthesized in the endoplasmic reticulum is preferentially metabolized to sphingomyelin in the distal Golgi region, how cholesterol and phospholipids receive specific metabolic reactions in mitochondria, and how the hijacking of host LTPs by intracellular pathogens may generate new channeling-like events. In addition, the article will discuss how the function of LTPs is regulated, exemplified by a few representative LTP systems, and will briefly touch on experiments that will be necessary to establish the paradigm that LTP-mediated inter-organelle transport of lipids is one of the mechanisms of compartmentalization-based metabolic channeling events.
各种脂质转移蛋白(LTPs)介导脂质在细胞器间的运输。通过在供体和受体细胞器之间的膜接触区工作,LTPs 实现了脂质在细胞器间的快速和准确转移。本文将描述一个新出现的范例,即 LTP 在细胞器接触区的作用会在脂质代谢中产生代谢通道事件,主要涉及内质网中合成的神经酰胺如何优先在远端高尔基体区域代谢为鞘磷脂,胆固醇和磷脂如何在线粒体中接受特定的代谢反应,以及细胞内病原体劫持宿主 LTP 如何可能产生新的类似通道事件。此外,本文将讨论 LTP 功能的调节方式,以一些有代表性的 LTP 系统为例,并简要讨论建立 LTP 介导的脂质在细胞器间运输是基于区室化的代谢通道事件的机制之一的范例所需的实验。