Figure 3.

A schematic summary of glycolysis, TCA cycle, and OXPHOS in regulating radioresistance. (1) In the cytoplasm, pyruvate produced by glycolysis crosses the outer mitochondrial membrane and participates in the TCA cycle, and the subsequently produced NADH and FADH₂ are oxidized by a stepwise, continuous enzymatic reaction on the ETC located in the inner mitochondrial membrane, thereby releasing energy for the body to utilize. (2) Inactivation of FH, SDH, D2HGDH, and L2HGDH, mutation of IDH1/2, or promiscuous activity of MDH/LDH can induce accumulation of oncometabolites. On the one hand, oncometabolites promote tumorigenesis; on the other hand, they also amplify the benefits of radiotherapy. (3) Enhancing OCR or favoring the reprogramming of tumor cells’ metabolic pathways induces radioresistance. Abbreviations: TCA cycle—tricarboxylic acid cycle, ETC—electron transport chain, OCR—oxygen consumption rate, FH —fumarate hydratase, SDH—succinate dehydrogenase, D2HGDH—D-2-hydroxyglutarate dehydrogenase, L2HGDH—L-2-hydroxyglutarate dehydrogenase, IDH1/2—isocitrate dehydrogenase-1/-2, LDH/MDH—lactate dehydrogenase/malate dehydrogenase, α-KG—α-ketoglutarate, D-2HG—D-2-hydroxyglutarate, L-2HG—L-2-hydroxyglutarate.