Histone lactylation: A key epigenetic modulator in the pathogenesis of metabolic dysfunction-associated steatohepatitis and alcoholic steatohepatitis

Figure 1 Molecular mechanism of histone lactylation. Lactate acts as a bio-signaling molecule beyond its metabolic role. Lactate transport from lactate transporters, such as monocarboxylate transporter 1 and 4, (MCT1/4) and its synthesis via glycolysis involving hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA) results in the conversion of lactate into lactyl-coenzyme A. Following this “writers” like p300 facilitate lactylation, while “erasers” such as histone deacetylases (HDACs) 1-3 and sirtuin 1-3 act as delactylases. The lactylation of histone 3 at lysine 18 results in the expression of target genes. GLUT: Glucose transporter; HATs: Histone acetyltransferases; la: Lactyl.