Intra-mitochondrial glycolysis maintains mitochondrial function and underlies the pathogenesis of retinitis pigmentosa
C] glucose isotope tracing, we demonstrate that key glycolytic enzymes are locally translated and metabolically active within the organelle. Mechanistically, we show that the VWA8-PHB2-GRP75 complex is responsible for anchoring these enzymes, thereby sustaining intra-mitochondrial glycolysis and preserving mitochondrial function by regulating NAD+ levels and reactive oxygen species (ROS) homeostasis. In vivo, Vwa8 knockout in both mice and zebrafish abolishes this metabolic safeguard, leading to RP-like phenotypes that can be partially rescued by reactivating mitochondrial glycolysis. Collectively, these findings redefine the spatial compartmentalization of glucose metabolism and establish mitochondrial glycolysis as a therapeutic target for mitochondrial diseases.
Authors
- Guojia Wan (ORCID: https://orcid.org/0000-0003-3151-8606)
- Yiwen He
- Xiaowei Wei (ORCID: https://orcid.org/0000-0003-2320-8982)
- Anhua Wu (ORCID: https://orcid.org/0000-0002-3402-1884)
- Songying Cao
- Linghui Kong (ORCID: https://orcid.org/0000-0001-7330-3967)
- Wenting Luo (ORCID: https://orcid.org/0000-0001-6494-9870)
- Dongxue Ding
- Bo Du
- Dan Liu
- Jiajian Liang
- Minghui Liao
- Chao Yang
- Hui Gu
- Shanshan Jia (ORCID: https://orcid.org/0000-0001-8413-9891)
- Yizhang Dong
- Zhengwei Yuan (ORCID: https://orcid.org/0000-0003-0967-9462)
- Wei Ma (ORCID: https://orcid.org/0000-0002-7362-6261)
Institutions
- Wuhan University (CN)
- Wuhan Business University (CN)
- First Hospital of China Medical University (CN)
- China Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-12
- DOI
- https://doi.org/10.1038/s41467-026-72988-3
- Primary Topic
- Retinal Development and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Key Research and Development Program of China