期刊
ONCOGENE
卷 21, 期 53, 页码 8149-8157出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1206053
关键词
apoptosis; Bcl-2; mitochondria; ultrastructure; membrane potential; permeability transition; oligomycin; tumor necrosis factor
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 alpha (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 F-1 component) do not affect apoptosis. A role of oligomycin-sensitive F-0 component of H+-ATP-synthase in the TNF-induced PTP opening and apoptosis is suggested.
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