Fig. 3

Schematic showing representative mitochondrial therapeutic targets and their proposed inhibitors. The mitochondrial ETC, as the central system of mitochondrial energy production and OXPHOS, has been the most frequently used mitochondrial target. Multiple mitochondrial ETC inhibitors, including metformin and IACS-010759, are being investigated for cancer treatment. In addition, inhibitors targeting different steps of the mitochondrial TCA cycle have shown promise in phase I and II clinical trials. Several other TCA cycle-coupled biomacromolecule synthesis pathways, such as the nucleotide synthesis pathway and the one-carbon (1C) metabolic pathway, are also potential therapeutic targets for reversing drug resistance