Endosomal lipid signaling reshapes the endoplasmic reticulum to control mitochondrial function
Endosomal lipid signaling reshapes the endoplasmic reticulum to control mitochondrial function
复制标题
DOI：
10.1126/science.abq5209
复制
发表时间：
2022-12-16
期刊：
影响因子：
56.9
通讯作者：
Haucke, Volker
中科院分区：
文献类型：
--
作者：
Jang, Wonyul;Puchkov, Dmytro;Haucke, Volker
细胞通过细胞器动力学和非代谢的适应性变化来响应波动的营养供应。这种变化是如何在细胞范围内协调的尚不清楚。我们发现，由MTM 1（一种在人类X连锁中枢性肌病中突变的磷脂酰肌醇3-磷酸[PI（3）P] 3-磷酸酶）引起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MTM 1的内体募集损害了管状ER膜和早期内体之间的PI（3）P依赖性接触形成，导致ER小管转化为片层，抑制线粒体分裂和持续的氧化代谢。我们的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，从而控制线粒体的形式和功能，使细胞能够适应波动的营养环境。
Cells respond to fluctuating nutrient supply by adaptive changes in organelle dynamics and inmetabolism. 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.