title: Oligomycin, inhibitor of the F0 part of H+-ATP-synthase, suppresses the TNF-induced apoptosis.
abstract: 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 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.
authors.affiliation: AN Belozersky Institute, MV Lomonosov Moscow State University, 4 Khokhlova str., Bldg, A, Moscow 119992, Russia.
authors.forename: Liarisa A
authors.initials: LA
authors.lastname: Shchepina
authors.forename: Olga Y
authors.initials: OY
authors.lastname: Pletjushkina
authors.forename: Armine V
authors.initials: AV
authors.lastname: Avetisyan
authors.forename: Liora E
authors.initials: LE
authors.lastname: Bakeeva
authors.forename: Elena K
authors.initials: EK
authors.lastname: Fetisova
authors.forename: Denis S
authors.initials: DS
authors.lastname: Izyumov
authors.forename: Valeria B
authors.initials: VB
authors.lastname: Saprunova
authors.forename: Mikhail Y
authors.initials: MY
authors.lastname: Vyssokikh
authors.forename: Boris V
authors.initials: BV
authors.lastname: Chernyak
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Skulachev
mesh_terms: D001313:Aurovertins / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D003847:Deoxyglucose / Q000494:pharmacology; D004640:Emetine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019254:Genes, bcl-2; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009840:Oligomycins / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D001313:Aurovertins; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009363:Neoplasm Proteins; D009840:Oligomycins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014475:Uncoupling Agents; C034402:aurovertin B; D016572:Cyclosporine; D003847:Deoxyglucose; D006180:Proton-Translocating ATPases; D019311:Staurosporine; D004640:Emetine