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.

journal_name

Oncogene

journal_title

Oncogene

authors

Shchepina LA,Pletjushkina OY,Avetisyan AV,Bakeeva LE,Fetisova EK,Izyumov DS,Saprunova VB,Vyssokikh MY,Chernyak BV,Skulachev VP

doi

10.1038/sj.onc.1206053

subject

Has Abstract

pub_date

2002-11-21 00:00:00

pages

8149-57

issue

53

eissn

0950-9232

issn

1476-5594

journal_volume

21

pub_type

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