Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

Oncogene volume 21, pages 8149–8157 (2002)Cite this article

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 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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Abbreviations

ANT:

adenine nucleotide translocator

CCCP:

carbonyl cyanide m-chlorophenylhydrazone

CsA:

Cyclosporin A

DCF:

dichlorofluorescine

DCFDA:

dichlorofluorescine diacetate

DMEM:

Dulbecco's modified Eagle's medium

DNP:

2,4-p-dinitrophenol

DOG:

2-deoxiglucose

MTT:

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

PTP:

permeability transition pore

Sts:

staurosporine

TFP:

trifluoropyrasine

TNF:

tumor necrosis factor α

References

  • Bradham CA, Qian T, Streetz K, Tratwein C, Brenner DA, Lemasters JJ . 1998 Mol. Cell. Biol. 18: 6353–6364

  • Broekemeier KM, Pfeiffer DR . 1995 Biochemistry 34: 16440–16449

  • Domnina LV, Ivanova OY, Chernyck BV, Skulachev VP, Vasiliev YM . 2002 Biochemistry (Moscow) 67: 737–746

  • Du C, Fang M, Li Y, Li L, Wang X . 2000 Cell 102: 33–42

  • Eguchi Y, Shimizu S, Tsujimoto Y . 1997 Cancer Res. 57: 1835–1840

  • Goldstein JC, Waterhouse NJ, Juin P, Evans GI, Green DR . 2000 Nature Cell. Biol. 2: 156–162

  • Hsu YT, Walter KG, Joule RJ . 1997 Proc. Natl. Acad. Sci. USA 94: 3668–3672

  • Ikemoto H, Tani E, Ozaki I, Kitagawa H, Arita N . 2000 Cell Death Diff. 7: 511–520

  • Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD . 1997 Science 275: 1132–1136

  • Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ, Shlesinger PH . 2000 Cell Death Diff. 7: 1166–1173

  • Kroemer G . 1997 Nature Med. 3: 614–620

  • Kroemer G, Dallaporta B, Reshe-Rigon M . 1998 Ann. Rev. Physiol. 60: 619–642

  • Kroemer G, Reed JC . 2000 Nature Med. 6: 513–519

  • Leist M, Single B, Castoldi AF, Kuhnle S, Nicotera P . 1997 J. Exp. Med. 185: 1481–1486

  • Li LY, Luo X, Wang X . 2001 Nature 412: 95–99

  • Liu Y, Peterson DA, Kimura H, Schubert D . 1997 J. Neurochem. 69: 581–593

  • Matsuyama S, Xu Q, Velours J, Reed JC . 1998 Mol. Cell 1: 327–336

  • Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H, Tsujimoto Y . 1998 Proc. Natl. Acad. Sci. USA 95: 14681–14686

  • Novgorodov SA, Gudz TI, Mohr Yu E, Goncharenko EN, Yaguzhinsky LS . 1989 FEBS Lett. 247: 255–258

  • Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S . 2002 Proc. Natl. Acad. Sci. USA 99: 1259–1263

  • Peachman KK, Lyles DS, Bass DA . 2001 Proc. Natl. Acad. Sci. USA 98: 1717–1722

  • Salomon AR, Voehringer DW, Herzenberg LA, Khosla C . 2000 Proc. Natl. Acad. Sci. USA 97: 14766–14771

  • Samali A, Cai J, Zhivotovsky B, Jones DP, Orrenius S . 1999 EMBO J. 18: 2040–2048

  • Scorrano L, Ashiya M, Buttle K, Weiler S, Oakes SA, Mannella CA, Korsmeyer SJ . 2002 Dev. Cell 2: 55–67

  • Shchepina LA, Popova EN, Pletjushkina OYu, Chernyak BV . 2002 Biochemistry (Moscow) 67: 222–226

  • Sidoti-de Fraisse C, Rincheval V, Risler Y, Mignotte B, Vayssiere J-L . 1998 Oncogene 17: 1639–1651

  • Skulachev VP . 1996a FEBS Lett. 397: 7–10

  • Skulachev VP . 1996b Quart. Rev. Biophys. 29: 169–202

  • Skulachev VP . 1998 FEBS Lett. 423: 275–280

  • Skulachev VP . 1999 Mol. Asp. Med. 20: 139–184

  • Tafani M, Minchenko DA, Serroni A, Farber JL . 2001 Cancer Res. 61: 2459–2466

  • Tafani M, Schneider TG, Pastorino JG, Farber JL . 2000 Am. J. Physiol. 156: 2111–2121

  • Vander Heiden MG, Chandel NS, Williamson EK, Schumacker PT, Thompson CB . 1997 Cell 91: 627–637

  • Verhagen AM, Ekert PG, Pakush M, Silke J, Connoly LM, Reid GE, Moritz RL, Simpson RJ, Vaux DL . 2000 Cell 102: 45–53

  • Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M, Thompson CB, Korsmeyer SJ . 2000 Genes Dev. 14: 2060–2071

  • Wolvetang EJ, Johnson KL, Krauer K, Ralph SJ, Linnane AW . 1994 FEBS Lett. 339: 40–44

  • Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng I-I, Jones DP, Wang X . 1997 Science 275: 1129–1132

  • Zhuang J, Dinsdale D, Cohen GM . 1998 Cell Death Diff. 5: 953–962

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

  1. AN Belozersky Institute, MV Lomonosov Moscow State University, 4 Khokhlova str., Bldg, A, 119992, Moscow, Russia

    Liarisa A Shchepina, Olga Y Pletjushkina, Armine V Avetisyan, Liora E Bakeeva, Elena K Fetisova, Denis S Izyumov, Valeria B Saprunova, Mikhail Y Vyssokikh, Boris V Chernyak & Vladimir P Skulachev

Authors
  1. Liarisa A Shchepina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olga Y Pletjushkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Armine V Avetisyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liora E Bakeeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elena K Fetisova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Denis S Izyumov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Valeria B Saprunova
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mikhail Y Vyssokikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Boris V Chernyak
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vladimir P Skulachev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Boris V Chernyak.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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). https://doi.org/10.1038/sj.onc.1206053

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206053

Keywords

This article is cited by

Search

Advanced search

Quick links