Mitochondrial L-2-hydroxyglutarate is a physiological signalling metabolite - PubMed
3 hours ago
- #metabolite signaling
- #epigenetic regulation
- #mitochondrial metabolism
- Mitochondrial L-2-HG acts as a physiological signaling metabolite, regulated by mitochondrial NADH/NAD+ ratio via MDH2 and oxidized back by L2HGDH.
- L-2-HG targets the KDM4 family of demethylases, increasing H3K9me3 levels and repressing specific gene transcription, including in mouse embryonic stem cells.
- Overexpression of L2HGDH in mice reduces L-2-HG, leading to impaired growth, mortality, and kidney issues, with H3K9me3 loss at retrotransposons triggering stress and inflammation.