Bax and Adenine Nucleotide Translocator Cooperate in the Mitochondrial Control of Apoptosis
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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Pro- and anti-apoptotic BCL2 family members such as BAX, BAK, BID, BCL2, and BCL-XL regulate MPT-driven necrosis.
“These include: (1) pro- and anti-apoptotic BCL2 family members such as BAX, BAK, and BID [407–410], as well as BCL2 and BCL-XL [411–414]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [409]
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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
- ORCID
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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