Fig. 3.

Schematic diagram of cross-talk between iron-related metabolism and hypoxia-inducible factor 1α (HIF-1α) in clear cell renal cell carcinoma. The cytosolic excess iron and hydrogen peroxide trigger the Fenton reaction with generation of reactive oxygen species, hydroxyl radicals, and hydroxide anions. To maintain the cytosolic and mitochondrial pH, glycolysis, lactate formation, and subsequent nucleotide synthesis is promoted. Inactivation of VHL induces the activation of HIF-1α, which promotes the expression of glycolysis-related genes and LDHA. FBXL5, F-Box and leucine rich repeat protein 5.