Fig. 3

Production of oncometabolites dysregulates epigenetics in cancer. Mutations in the metabolic enzymes IDH, FH, and SDH (red) promote the generation, respectively, of the oncometabolites 2-HG, fumarate, and succinate. Hypoxia causes LDH and MDH (grey) to produce 2-HG, which acts as a competitive inhibitor of α-KG-dependent dioxygenase to deregulate DNA and histone methylation. This leads to aberrant gene expression and cancer