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

Shchepina, Liarisa A.; Pletjushkina, Olga Yu.; Avetisyan, A. V.; Bakeeva, L. E.; Fetisova, E. K.; Izyumov, D. S.; Saprunova, V. B.; Vysokikh, Mikhail; Chernyak, Boris V.; Vp, Skulachev

doi:10.1038/sj.onc.1206053

Cited by 148 publications

(126 citation statements)

References 36 publications

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“…15 As examples, reports show that a functional electron transport chain regulates oxygen deprivation-induced cell death, and an ATP synthase is required in TNF-induced apoptosis. [37][38][39] In this study, using a lossof-function approach, we demonstrated that the function of complex I is necessary for IFN/RA-induced cancer cell death, suggesting that changes in cellular metabolism can directly affect the sensitivity of a cell to apoptosis induced by specific agents. Our data provide another example where mitochondrial physiology plays a direct role in apoptotic cell death.…”

Section: Discussionmentioning

confidence: 76%

Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-β and retinoic acid-induced cancer cell death

Huang

Chen

et al. 2006

Cell Death Differ

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Combination of retinoic acids (RAs) and interferons (IFNs) has synergistic apoptotic effects and is used in cancer treatment. However, the underlying mechanisms remain unknown. Here, we demonstrate that mitochondrial respiratory chain (MRC) plays an essential role in the IFN-b/RA-induced cancer cell death. We found that IFN-b/RA upregulates the expression of MRC complex subunits. Mitochondrial-nuclear translocation of these subunits was not observed, but overproduction of reactive oxygen species (ROS), which causes loss of mitochondrial function, was detected upon IFN-b/RA treatment. Knockdown of GRIM-19 (gene associated with retinoid-interferon-induced mortality-19) and NDUFS3 (NADH dehydrogenase (ubiquinone) Fe-S protein 3), two subunits of MRC complex I, by siRNA in two cancer cell lines conferred resistance to IFN-b/RA-induced apoptosis and reduced ROS production. In parallel, expression of late genes induced by IFN-b/RA that are directly involved in growth inhibition and cell death was also repressed in the knockdown cells. Our data suggest that the MRC regulates IFN-b/RA-induced cell death by modulating ROS production and late gene expression.

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Section: Discussionmentioning

confidence: 76%

Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-β and retinoic acid-induced cancer cell death

Huang

Chen

et al. 2006

Cell Death Differ

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“…31 In addition, CYPD as well as two distinct anti-apoptotic members of the BCL-2 family, namely BCL-X L and MCL-1, have recently been reported to regulate mitochondrial ATP synthesis by physically interacting with the F 1 F O ATP synthase. [32][33][34][35] Driven by these observations and by the facts that: (1) a selective inhibitor of the F O subunit of ATP synthase, i.e., oligomycin, is able to prevent cell death as induced by tumor necrosis factor α (TNFα), 36 the multi-kinase inhibitor staurosporine 37 or BAX overexpression; 38 and that (2) the activity of both the PTPC and F 1 F O ATP synthase is modulated by Mg 2+ ions; 39,40 we decided to investigate the role of F O ATP synthase subunits in MPT.…”

Section: Resultsmentioning

confidence: 99%

Role of the c subunit of the F_OATP synthase in mitochondrial permeability transition

et al. 2013

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“…Few if any such OMM breaks were observed in Jurkat cells exposed to ABT-737 but rather the mitochondria appeared ultracondensed (Figure 7c), as observed in our earlier study. 47 Ultracondensed mitochondria have also been reported as a consequence of mitochondrial swelling during cell death 48 but condensed mitochondria were rare in primary leukemia or lymphoma cells following exposure to ABT-737. In preliminary studies, in several human cancer cell lines including several mantle cell lymphoma lines (such as Z138), micromolar concentrations of ABT-737 were required to induce rapid apoptosis.…”

Section: Discussionmentioning

confidence: 99%

A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells

et al. 2008

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Primary chronic lymphocytic leukemia (CLL) cells are exquisitely sensitive to ABT-737, a small molecule BCL2-antagonist, which induces many of the classical biochemical and ultrastructural features of apoptosis, including BAX/BAK oligomerization, cytochrome c release, caspase activation and chromatin condensation. Surprisingly, ABT-737 also induces mitochondrial inner membrane permeabilization (MIMP) resulting in mitochondrial matrix swelling and rupture of the outer mitochondrial membrane (OMM), so permitting the rapid efflux of cytochrome c from mitochondrial cristae and facilitating rapid caspase activation and apoptosis. BAX and BAK appear to be involved in the OMM discontinuities as they localize to the OMM break points. Notably, ABT-737 induced mitochondrial matrix swelling and OMM discontinuities in other primary B-cell malignancies, including mantle cell, follicular and marginal zone lymphoma cells but not in several cell lines studied. Thus, we describe a new paradigm of apoptosis in primary B-cell malignancies, whereby targeting of BCL2 results in all the classical features of apoptosis together with OMM rupture independent of caspase activation. This mechanism may be far more prevalent than hitherto recognized due to the failure of most methods, used to measure apoptosis, to recognize such a mechanism.

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

Cited by 148 publications

References 36 publications

Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-β and retinoic acid-induced cancer cell death

Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-β and retinoic acid-induced cancer cell death

Role of the c subunit of the F_OATP synthase in mitochondrial permeability transition

A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells

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

Cited by 148 publications

References 36 publications

Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-β and retinoic acid-induced cancer cell death

Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-β and retinoic acid-induced cancer cell death

Role of the c subunit of the FOATP synthase in mitochondrial permeability transition

A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells

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Role of the c subunit of the F_OATP synthase in mitochondrial permeability transition