Oligomycin Complex

Oligomycin complex consists of a blend of oligomycins A, B, and C. Oligomycin is a class of similar 26-membered macrolide antibiotics isolated from Streptomyces amylase chromogenes. Oligomycin has antifungal activity, oxidative phosphorylation inhibition and insecticidal activity[1].Oligomycin A primarily exerts its inhibitory effect on mitochondrial oxidative phosphorylation by blocking the proton channel (F0 subunit) of ATP synthase, thus inhibiting ATP synthesis. Additionally, it reduces the compensatory increase in oxidative phosphorylation in tumor cells, leading to a decrease in cellular glycolysis levels[2-4].Oligomycin B acts as a non-selective inhibitor of ATP synthases, effectively slowing down ATP depletion in cases of myocardial ischemia. Oligomycin C is an inhibitor of mitochondrial F1F0-ATP synthase, which induces more sensitive cell death and shifts the cell death pattern from apoptosis to necrosis.

Oligomycin(0-50µg/ml; 24h) induced mitochondrial membrane depolarization and cytochrome c release in HepG2 and R-HepG2 cells[5].Oligomycin A(0-16 µM;12-48 h) promotes HT29 cell survival and proliferation[6]. In A549 cells, 100 ng/ml Oligomycin could completely inhibit OXPHOS phosphorylation activity in 1 hour and stimulate various levels of glycolysis gains[7]. 5 µg/ml Oligomycin could inhibit the F0 part of H+-ATP-synthase, and strongly suppress cytochrome c release and apoptosis in Hela cells induced by TNF[8]. Oligomycin B(1 µM) induced vasodilations that were 39-61% smaller in sulfonylurea receptor 2 null (SUR2(nl)) than in SUR2 wild-type (SUR2(wt)) arteries[9].

References:
[1]. SMITH RM, PETERSON WH, et,al.Oligomycin, a new antifungal antibiotic. Antibiot Chemother (Northfield). 1954 Sep;4(9):962-70. PMID: 24543225.
[2]. Vestergaard M, NØhr-Meldgaard K, et al. Inhibition of the ATP synthase eliminates the intrinsic resistance of Staphylococcus aureustowards polymyxins[J].mBio, 2017, 8(5): e01114-17.
[3]. Untereiner AA, Pavlidou A, et al. Drug resistance induces the upregulation of H2S-producing enzymes in HCT116 colon cancer cells[J].Biochem Pharmacol, 2018, 149: 174-185.
[4]. Ruas JS, Siqueira-Santos ES, et al. High glycolytic activity of tumor cells leads to underestimation of electron transport system capacity when mitochondrial ATP synthase is inhibited[J].Sci Rep, 2018, 8(1): 17383.
[5]. Li YC, Fung KP, et,al. Mitochondria-targeting drug oligomycin blocked P-glycoprotein activity and triggered apoptosis in doxorubicin-resistant HepG2 cells. Chemotherapy. 2004 Jun;50(2):55-62. doi: 10.1159/000077803. PMID: 15211078.
[6]. Li X, Tian R, et,al. Oligomycin A promotes radioresistance in HT29 colorectal cancer cells and its mechanisms. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2021 Feb 28;46(2):113-120. English, Chinese. doi: 10.11817/j.issn.1672-7347.2021.200063. PMID: 33678646.
[7]. Hao W, Chang CP, et al. Oligomycin-induced bioenergetic adaptation in cancer cells with heterogeneous bioenergetic organization. J Biol Chem. 2010 Apr 23;285(17):12647-54. doi: 10.1074/jbc.M109.084194. Epub 2010 Jan 28. PMID: 20110356; PMCID: PMC2857128.
[8]. Shchepina LA, Pletjushkina OY, et al. Oligomycin, inhibitor of the F0 part of H+-ATP-synthase, suppresses the TNF-induced apoptosis. Oncogene. 2002 Nov 21;21(53):8149-57. doi: 10.1038/sj.onc.1206053. PMID: 12444550.
[9]. Adebiyi A, McNally EM, et al. Vasodilation induced by oxygen/glucose deprivation is attenuated in cerebral arteries of SUR2 null mice. Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1360-8. doi: 10.1152/ajpheart.00406.2011. Epub 2011 Jul 22. PMID: 21784985; PMCID: PMC3197357.