Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c (original) (raw)

Nature volume 391, pages 496–499 (1998)Cite this article

Abstract

Following exposure of cells to stimuli that trigger programmed cell death (apoptosis), cytochrome c is rapidly released from mitochondria into the cytoplasm where it activates proteolytic molecules known as caspases that specifically cleave the amino-acid sequence DEVD and are crucial for the execution of apoptosis1,2,3,4. The protein Bcl-2 interferes with this activation of caspases by preventing the release of cytochrome c2,3,4. Here we study these molecular interactions during apoptosis induced by the protein Bax, a pro-apoptotic homologue of Bcl-2 (refs 5, 6). We show that in cells transiently transfected with bax, Bax localizes to mitochondria and induces the release of cytochrome c, activation of caspase-3, membrane blebbing, nuclear fragmentation, and cell death. Caspase inibitors do not affect Bax-induced cytochrome c release but block caspase-3 activation and nuclear fragmentation. Unexpectedly, Bcl-2 also fails to prevent Bax-induced cytochrome c release, although it co-localizes with Bax to mitochondria. Cells overexpressing both Bcl-2 and Bax show no signs of caspase activation and survive with significant amounts of cytochrome c in the cytoplasm. These findings indicate that Bcl-2 can interfere with Bax killing downstream of and independently of cytochrome c release.

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Acknowledgements

We thank D. Nicholson for the anti-caspase-3 antibody, and S. Rusconi, J.-L. Dreyer and M. Wymann for critically reading the manuscript. This research was supported by the Swiss National Science Foundation, the Swiss Cancer League and the Foundation for Aging Research (AETAS). B.J. was supported by the Austrian Science Foundation.

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Authors and Affiliations

  1. Institute of Biochemistry, University of Fribourg, Rue du Museé 5, Fribourg, CH-1700, Switzerland
    Thierry Rossé, Reynald Olivier, Laurent Monney, Monika Rager, Sébastien Conus, Isabelle Fellay & Christoph Borner
  2. Department of Clinical Pharmacology, Section of Experimental Oncology and Department of Dermatology, Division of General Dermatology, Vienna General Hospital, University of Vienna, Whringer Grtel 18-20, Vienna, A-1090, Austria
    Burkhard Jansen

Authors

  1. Thierry Rossé
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  2. Reynald Olivier
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  3. Laurent Monney
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  4. Monika Rager
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  5. Sébastien Conus
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  6. Isabelle Fellay
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  7. Burkhard Jansen
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  8. Christoph Borner
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Correspondence toChristoph Borner.

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Rossé, T., Olivier, R., Monney, L. et al. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c.Nature 391, 496–499 (1998). https://doi.org/10.1038/35160

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