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. Author manuscript; available in PMC: 2015 Jul 1.
Published in final edited form as: Nat Chem Biol. 2015 Jan;11(1):9–15. doi: 10.1038/nchembio.1712

Figure 2. Targeting mitochondrial bioenergetic capacity.

Figure 2

Mitochondrial ATP generation is necessary for tumorigenesis, and few molecules have demonstrated success in preclinical models of cancer. Specifically, (1) the biguanides metformin and phenformin inhibit mitochondrial complex I; (2) VLX600 inhibits the ETC at multiple sites; (3) tigecycline inhibits the mitochondrial ribosomal machinery and consequently the translation of ETC subunits; (4) gamitrinib is an inhibitor of mitochondrial chaperone proteins, such as TRAP-1 and HSP-90. Loss of these chaperones decreases ETC complex stability and subsequently reduces electron transport function. These therapies all share the same ultimate outcome with a decrease in mitochondrial ETC function to reduce mitochondrial bioenergetic capacity. mtDNA, mitochondrial DNA.