Antimycin A, an antibiotic produced by Streptomyces species that demonstrates antifungal, insecticidal, nematocidal, and piscicidal properties, is a mixture of Antimycins A1, A2, A3, and A4. [1] It blocks mitochondrial respiration and can deplete cellular levels of ATP via inhibition of complex III of the mitochondrial electron transport chain (ETC). Antimycin A prevents the transfer of electrons between the b-cytochromes and ubiquinone at the Q(inner) site of complex III. This results in the stabilization of the ubisemiquinone radical at the Q(outer) site of complex III, leading to increased production of superoxide. [2][3] Antimycin A is widely used in research to shunt electron flow through the ETC in order to study the chemical details of oxygen respiration. Additionally, antimycin A has been shown to inhibit Bcl-2 and Bcl-xL proteins, inducing apoptosis.[3][4][5]
Reference:
[1]. Seipke, R.F., and Hutchings, M.I. The regulation and biosynthesis of antimycins. Beilstein J.Org.Chem. 9, 2556-2563 (2013).
[2]. Muller, F., Crofts, A.R., and Kramer, D.M. Multiple Q-cycle bypass reactions at the Qo site of the cytochrome bc1 complex. Biochemistry 41(25), 7866-7874 (2002).
[3]. Muller, F.L., Roberts, A.G., Bowman, M.K., et al. Architecture of the Qo site of the cytochrome bc1 complex probed by superoxide production. Biochem. 42(21), 6493-6499 (2003).
[4]. Azmi, A.S., and Mohammad, R.M. Non-peptidic small molecule inhibitors against Bcl-2 for cancer therapy. J.Cell Physiol. 218(1), 13-21 (2009).
[5]. Marton, A., Mihalik, R., Bratincsak, A., et al. Apoptotic cell death induced by inhibitors of energy conservation--Bcl-2 inhibits apoptosis downstream of a fall of ATP level. Eur. J. Biochem. 250(2), 467-475 (1997).