Figure 1. Mitochondria function as bioenergetic, biosynthetic and signaling organelles.

Cancer cells catabolize pyruvate and glutamine through the TCA cycle, resulting in the generation of reducing equivalents such as NADH that donate electrons to the ETC. The ETC generates a proton gradient that is used for production of ATP, i.e., oxidative phosphorylation (blue). TCA cycle intermediates can also be directed into biosynthetic pathways (green) that allow for the production of macromolecules (lipids, amino acids and nucleotides). Finally, mitochondrial production of ROS and metabolites act as signaling molecules to alter protein function. Mitochondrial one-carbon metabolism produces NADPH to prevent accumulation of ROS in the mitochondrial matrix. NADPH maintains antioxidant activity of glutathione peroxidase (GPX) and thioredoxin reductases (TrxRs). TA, aminotransferase; VDAC, voltage-dependent anion channel. TRX, thioredoxin; GSH, glutathione; SOD2, superoxide dismutase 2, mitochondrial; 5,10-CH₂-THF, 5,10-methylene-tetrahydrofolate.