Mitochondrial l-2-hydroxyglutarate is a physiological signalling metabolite

l-2-Hydroxyglutarate (l-2-HG) is a low-abundance metabolite in mammals because the mitochondrial enzyme l-2-HG dehydrogenase (L2HGDH) oxidizes l-2-HG to 2-oxoglutarate (2-OG) to prevent its accumulation1. In humans, a lack of L2HGDH activity leads to l-2-HG accumulation and causes l-2-hydroxyglutaric aciduria2.