Lysosomal phosphoinositide turnover acts upstream of RagGTPase-mTORC1 and controls muscle growth - PubMed
3 hours ago
- #lysosome
- #mTORC1
- #muscle growth
- Lysosomal phosphoinositides (PI3P and PI(3,5)P2) regulate lysosomal adaptor and MAPK/mTOR activator complex stability.
- MTM1, a phosphoinositide 3-phosphatase mutated in myotubular myopathy, controls these lipid pools via ER-lysosome membrane contact sites.
- ER stress triggers MTM1-dependent phosphoinositide remodeling, suppressing RagGTPase-mTORC1 signaling to balance anabolic-catabolic processes during myogenic differentiation.
- Restoring mTORC1 activity or lysosomal phosphoinositide homeostasis rescues Rag-dependent signaling and muscle growth in myopathy models.
- The study identifies lysosomal phosphoinositides as metabolic checkpoints with direct relevance to muscle diseases.