The pro-apoptotic protein Bax plays a key role in the mitochondrial signalling pathway. Upon induction of apoptosis, Bax undergoes a conformational change and translocates to mitochondrial membranes, where it inserts and mediates the release of cytochrome c from the intermembrane space into the cytosol. However, the domains of Bax that are essential for the induction of cytochrome c release are still elusive. Therefore various Bax deletion mutants were generated and expressed in Escherichia coli. The proteins were then purified in order to delineate the function of the transmembrane domain, the BH3 (Bcl-2 homology 3) domain and the putative pore-forming α-helices-5 and -6. These proteins were used to analyse the mechanism of Bax-induced cytochrome c release from mitochondria. None of the Bax proteins caused cytochrome c release merely through physical perturbation of the mitochondrial outer membrane. The α-helices-5 and -6 of Bax were shown to mediate the insertion of the protein into mitochondrial membranes and to be essential for the cytochrome c-releasing activity of Bax. In contrast, neither the transmembrane domain nor a functional BH3 domain is required for the Bax-mediated release of cytochrome c from mitochondria.
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Research Article|
February 15 2004
Bax-induced cytochrome c release from mitochondria depends on alpha-helices-5 and -6
Gerd HEIMLICH;
Gerd HEIMLICH
*Institute for Medical Microbiology, Immunology and Hygiene, University of Köln, 50935 Köln, Germany
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Alastair D. McKINNON;
Alastair D. McKINNON
†Histology & TEM Facility, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, U.K.
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Katussevani BERNARDO;
Katussevani BERNARDO
*Institute for Medical Microbiology, Immunology and Hygiene, University of Köln, 50935 Köln, Germany
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Dieter BRDICZKA;
Dieter BRDICZKA
‡Department of Biology, University of Konstanz, Konstanz, Germany
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John C. REED;
John C. REED
§The Burnham Institute, La Jolla, CA 92037, U.S.A.
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Renate KAIN;
Renate KAIN
‖Department of Pathology, University of Aberdeen, Aberdeen, U.K.
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Martin KRÖNKE;
Martin KRÖNKE
*Institute for Medical Microbiology, Immunology and Hygiene, University of Köln, 50935 Köln, Germany
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Juliane M. JÜRGENSMEIER
Juliane M. JÜRGENSMEIER
1
*Institute for Medical Microbiology, Immunology and Hygiene, University of Köln, 50935 Köln, Germany
1To whom correspondence should be sent, at present address: Cancer & Infection Bioscience, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, U.K. (e-mail Juliane.Jurgensmeier@astrazeneca.com).
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Publisher: Portland Press Ltd
Received:
July 30 2003
Revision Received:
October 31 2003
Accepted:
November 13 2003
Accepted Manuscript online:
November 13 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 378 (1): 247–255.
Article history
Received:
July 30 2003
Revision Received:
October 31 2003
Accepted:
November 13 2003
Accepted Manuscript online:
November 13 2003
Citation
Gerd HEIMLICH, Alastair D. McKINNON, Katussevani BERNARDO, Dieter BRDICZKA, John C. REED, Renate KAIN, Martin KRÖNKE, Juliane M. JÜRGENSMEIER; Bax-induced cytochrome c release from mitochondria depends on alpha-helices-5 and -6. Biochem J 15 February 2004; 378 (1): 247–255. doi: https://doi.org/10.1042/bj20031152
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