Mitochondrial L-2-hydroxyglutarate: Rethinking metabolite repair as physiological signaling
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REFERENCES
[1] Chakrabarty R. P., Van Vranken J. G., Aoi Y., et al. (2026). Mitochondrial L-2-hydroxyglutarate is a physiological signalling metabolite. Nature 655:1037−1047. DOI:10.1038/s41586-026-10564-x [2] Chakrabarty R. P. and Chandel N. S. (2021). Mitochondria as signaling organelles control mammalian stem cell fate. Cell Stem Cell 28:394−408. DOI:10.1016/j.stem.2021.02.011 [3] Williams N. C., Ryan D. G., Costa A. S. H., et al. (2022). Signaling metabolite L-2-hydroxyglutarate activates the transcription factor HIF-1alpha in lipopolysaccharide-activated macrophages. J. Biol. Chem. 298:101501. DOI:10.1016/j.jbc.2021.101501 [4] Yang Y., Li X., Liu F., et al. (2025). Immunometabolite L-2-HG promotes epigenetic modification of exhausted T cells and improves antitumor immunity. J. Clin. Invest. Insight 10:e174600. DOI:10.1172/jci.insight.174600 [5] Yang Q., Hao J., Chi M., et al. (2022). D2HGDH-mediated D2HG catabolism enhances the anti-tumor activities of CAR-T cells in an immunosuppressive microenvironment. Mol. Ther. 30:1188−1200. DOI:10.1016/j.ymthe.2022.01.007 -
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Bai D., Zhou Y. and Yang Q. (2027). Mitochondrial L-2-hydroxyglutarate: Rethinking metabolite repair as physiological signaling. The Innovation Life 5:100260. https://doi.org/10.59717/j.xinn-life.2026.100260
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Bai D., Zhou Y. and Yang Q. (2027). Mitochondrial L-2-hydroxyglutarate: Rethinking metabolite repair as physiological signaling. The Innovation Life 5:100260. https://doi.org/10.59717/j.xinn-life.2026.100260
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Figure 1.
Schematic model of mitochondrial L-2-HG as a physiological signaling metabolite
