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Cited by 1,521

The DOI matches its Crossref record.

Bax directly induces release of cytochrome c from isolated mitochondria

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Jürgensmeier, Juliane M., Xie, Zhihua, Deveraux, Quinn, Ellerby, Lisa, Bredesen, Dale, Reed, John C.·1998·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.95.9.4997
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Abstract

Bax is a pro-apoptotic member of the Bcl-2 protein family that resides in the outer mitochondrial membrane. It is controversial whether Bax promotes cell death directly through its putative function as a channel protein versus indirectly by inhibiting cellular regulators of the cell death proteases (caspases). We show here that addition of submicromolar amounts of recombinant Bax protein to isolated mitochondria can induce cytochrome c (Cyt c ) release, whereas a peptide representing the Bax BH3 domain was inactive. When placed into purified cytosol, neither mitochondria nor Bax individually induced proteolytic processing and activation of caspases. In contrast, the combination of Bax and mitochondria triggered release of Cyt c from mitochondria and induced caspase activation in cytosols. Supernatants from Bax-treated mitochondria also induced caspase processing and activation. Recombinant Bcl-X L protein abrogated Bax-induced release of Cyt c from isolated mitochondria and prevented caspase activation. In contrast, the broad-specificity caspase inhibitor benzyloxycarbonyl-valinyl-alaninyl-aspartyl-( 0 -methyl)-fluoromethylketone (zVAD-fmk) and the caspase-inhibiting protein X-IAP had no effect on Bax-induced release of Cyt c from mitochondria in vitro but prevented the subsequent activation of caspases in cytosolic extracts. Unlike Ca 2+ , a classical inducer of mitochondrial permeability transition, Bax did not induce swelling of mitochondria in vitro . Because the organellar swelling caused by permeability transition causes outer membrane rupture, the findings, therefore, dissociate these two events, implying that Bax uses an alternative mechanism for triggering release of Cyt c from mitochondria.

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Metadata

Authors
Jürgensmeier, J. M., Xie, Z., Deveraux, Q., Ellerby, L., Bredesen, D., & Reed, J. C.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
1998-04-28
Volume
95
Issue
9
Pages
4997-5002
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.95.9.4997
OpenAlex
W2013319326
Cited by
1,521
References
0
FWCI
47.95
Type
journal article
Language
en
Open access
green

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