研究人员表明，MTM1（一种在人类X连锁核心肌病中突变的磷脂酰肌醇3-磷酸[PI(3)P]3-磷酸酶）的内体信号脂质周转，通过重塑内质网（ER）控制线粒体形态和功能。饥饿诱导的MTM1内体招募损害了PI(3)P依赖性的管状ER膜和早期内体之间的接触形成，导致ER小管转化为片状，抑制线粒体分裂，并持续氧化代谢。这些研究结果揭示了早期内体脂质信号在控制ER形状中的重要作用，从而控制线粒体形态和功能，使细胞适应波动的营养环境。
据悉，细胞通过细胞器动态和新陈代谢的适应性变化对波动的营养供应作出反应。这种变化是如何在全细胞范围内进行协调的，目前尚不清楚。
附：英文原文
Title: Endosomal lipid signaling reshapes the endoplasmic reticulum to control mitochondrial function
Author: Wonyul Jang, Dmytro Puchkov, Paula Samsó, YongTian Liang, Michal Nadler-Holly, Stephan J. Sigrist, Ulrich Kintscher, Fan Liu, Kamel Mamchaoui, Vincent Mouly, Volker Haucke
Issue&Volume: 2022-12-16
Abstract: Cells respond to fluctuating nutrient supply by adaptive changes in organelle dynamics and in metabolism. How such changes are orchestrated on a cell-wide scale is unknown. We show that endosomal signaling lipid turnover by MTM1, a phosphatidylinositol 3-phosphate [PI(3)P] 3-phosphatase mutated in X-linked centronuclear myopathy in humans, controls mitochondrial morphology and function by reshaping the endoplasmic reticulum (ER). Starvation-induced endosomal recruitment of MTM1 impairs PI(3)P-dependent contact formation between tubular ER membranes and early endosomes, resulting in the conversion of ER tubules into sheets, the inhibition of mitochondrial fission, and sustained oxidative metabolism. Our results unravel an important role for early endosomal lipid signaling in controlling ER shape and, thereby, mitochondrial form and function to enable cells to adapt to fluctuating nutrient environments.
DOI: abq5209
Source: https://www.science.org/doi/10.1126/science.abq5209