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Endosomal lipid signaling reshapes the endoplasmic reticulum to control mitochondrial function
Cited 13 time in
Web of Science
Cited 16 time in Scopus
- Authors
- Issue Date
- 2022-12
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE
- Citation
- SCIENCE, Vol.378 No.6625, pp.1188-+
- Abstract
- 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.
- ISSN
- 0036-8075
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