Intra-mitochondrial glycolysis maintains mitochondrial function and underlies the pathogenesis of retinitis pigmentosa - PubMed
3 hours ago
- #mitochondrial glycolysis
- #retinitis pigmentosa
- #VWA8 complex
- A complete and functional glycolytic pathway operates inside mitochondria, challenging the classical view of glycolysis as a cytoplasmic process.
- Key glycolytic enzymes are locally translated and metabolically active within mitochondria, as shown by CoIP-MS, polysome profiling, and isotope tracing.
- The VWA8-PHB2-GRP75 complex anchors glycolytic enzymes to sustain intra-mitochondrial glycolysis, regulating NAD+ levels and ROS homeostasis to preserve mitochondrial function.
- In vivo knockout of Vwa8 in mice and zebrafish abolishes this metabolic safeguard, leading to retinitis pigmentosa (RP)-like phenotypes.
- Reactivating mitochondrial glycolysis can partially rescue these RP-like phenotypes, suggesting it as a therapeutic target for mitochondrial diseases.