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Oligomycin, inhibitor of the F0 part of H+-ATP-synthase, suppresses the TNF-induced apoptosis


The release of cytochrome c from the intermembrane space of mitochondria into the cytosol is one of the critical events in apoptotic cell death. In the present study, it is shown that release of cytochrome c and apoptosis induced by tumor necrosis factor α (TNF) in HeLa cells can be inhibited by (i) overexpression of an oncoprotein Bcl-2, (ii) Cyclosporin A, an inhibitor of the mitochondrial permeability transition pore (PTP) or (iii) oligomycin, an inhibitor of H+- ATP-synthase. Staurosporine-induced apoptosis is sensitive to Bcl-2 but insensitive to Cyclosporin A and oligomycin. The effect of oligomycin is not due to changes in mitochondrial membrane potential or to inhibition of ATP synthesis/hydrolysis since (a) uncouplers (CCCP, DNP) which discharge the membrane potential fail to abolish the protective action of oligomycin and (b) aurovertin B (another inhibitor of H+-ATP-synthase, affecting its F1 component) do not affect apoptosis. A role of oligomycin-sensitive F0 component of H+-ATP-synthase in the TNF-induced PTP opening and apoptosis is suggested.

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adenine nucleotide translocator


carbonyl cyanide m-chlorophenylhydrazone


Cyclosporin A




dichlorofluorescine diacetate


Dulbecco's modified Eagle's medium






3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


permeability transition pore






tumor necrosis factor α


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The authors wish to thank Professor YM Vasiliev for intellectual support and helpful discussions, Dr LV Domnina, Dr OY Ivanova and Ms N Korovkina for help in some experiments, Dr G Belov for cells lines, and Dr V Korobko for a sample of TNF. This work was supported by Ludwig Cancer Research Institute Grant ROB 0863 and by RFBR Grants No 00-04-48090, 01-04-06048; 99-04-49256, 00-15-97799, 01-04-48606.

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Correspondence to Boris V Chernyak.

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Shchepina, L., Pletjushkina, O., Avetisyan, A. et al. Oligomycin, inhibitor of the F0 part of H+-ATP-synthase, suppresses the TNF-induced apoptosis. Oncogene 21, 8149–8157 (2002).

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