Cited by 1,168Cell death mechanisms and regulationMitochondrial Function and PathologyCardiac Ischemia and Reperfusion

Bax and Adenine Nucleotide Translocator Cooperate in the Mitochondrial Control of Apoptosis

Marzo, Isabel, Brenner, Catherine, Zamzami, Naoufal, Jürgensmeier, Juliane M., Susin, Santos A., Vieira, Helena L. A., Prévost, Marie-Christine, Xie, Zhihua +3 more·1998·Science

Abstract

The proapoptotic Bax protein induces cell death by acting on mitochondria. Bax binds to the permeability transition pore complex (PTPC), a composite proteaceous channel that is involved in the regulation of mitochondrial membrane permeability. Immunodepletion of Bax from PTPC or purification of PTPC from Bax-deficient mice yielded a PTPC that could not permeabilize membranes in response to atractyloside, a proapoptotic ligand of the adenine nucleotide translocator (ANT). Bax and ANT coimmunoprecipitated and interacted in the yeast two-hybrid system. Ectopic expression of Bax induced cell death in wild-type but not in ANT-deficient yeast. Recombinant Bax and purified ANT, but neither of them alone, efficiently formed atractyloside-responsive channels in artificial membranes. Hence, the proapoptotic molecule Bax and the constitutive mitochondrial protein ANT cooperate within the PTPC to increase mitochondrial membrane permeability and to trigger cell death.

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Crossref · 10.1126/science.281.5385.2027

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Authors
Marzo, I., Brenner, C., Zamzami, N., Jürgensmeier, J. M., Susin, S. A., Vieira, H. L. A., Prévost, M.-C., Xie, Z., Matsuyama, S., Reed, J. C., & Kroemer, G.
Affiliations
  • Université de Technologie de Compiègne (FR)
  • I. Marzo, N. Zamzami, S. A. Susin, H. L. A. Vieira, G. Kroemer, CNRS, UPR 420, 19 rue Guy Môquet, F-94801 Villejuif, France. C. Brenner, CNRS, UPR 420, 19 rue Guy Môquet, F-94801 Villejuif, France, and CNRS, UPRES-A6022, Université de Technologie de Compiègne, F-60200 Compiègne, France. J. M. Jürgensmeier, Z. Xie, S. Matsuyama, J. C. Reed, Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. M.-C. Prévost, Unité d'Oncologie Virale, Institut Pasteur, 28 rue du Docteur...
Corresponding author
  • Marzo, Isabel
  • Brenner, Catherine
  • Kroemer, Guido
Venue
Science
Published
1998-09-25
Volume
281
Issue
5385
Pages
2027-2031
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2167293805
Cited by
1,168
References
44
Citations by year
2025: 4 · 2024: 6 · 2023: 7 · 2022: 15 · 2021: 15 · 2020: 16 · 2019: 13 · 2018: 15 · 2017: 29 · 2016: 21 · 2015: 28 · 2014: 22 · 2013: 29 · 2012: 35
FWCI
40.24
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Keywords
Bax, adenine nucleotide translocase, apoptosis, mitochondrial permeability transition pore, mitochondrial membrane permeability, atractyloside, protein-protein interaction, cell death
MeSH terms
Mitochondrial ADP, ATP Translocases, Animals, Atractyloside, Binding Sites, Bongkrekic Acid, Humans, Intracellular Membranes, Liposomes, Mice, Inbred C57BL, Mitochondria, Permeability, Proto-Oncogene Proteins, Recombinant Proteins, Saccharomyces cerevisiae, Transfection, Cyclosporine, Rats, Wistar, Apoptosis, HT29 Cells, Proto-Oncogene Proteins c-bcl-2, Dimerization, bcl-2-Associated X Protein, Mice, Rats

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