Fig. 1

Schematic diagram of the lactate shuttle. In the cytoplasm, lactate is transformed into pyruvic acid under the catalysis of LDHB and then enters the mitochondrial tricarboxylic acid cycle (TAC). In addition, lactate can enter the mitochondria directly through the lactate oxidation complex (LOC) on the inner mitochondrial membrane and be converted into pyruvic acid. Lactate is also the precursor of gluconeogenesis. Lactate can be used as a substrate for posttranslational modification (PTM), causing the lactylation of histones and nonhistones, and can then regulate gene expression or protein function. Abbreviations: TAC: tricarboxylic acid cycle; PTM: posttranslational modification; LOC: lactate oxidation complex; PKM2: M2-type pyruvate kinase; AK2: adenylate kinase 2