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Cited by 284Cell death mechanisms and regulationMitochondrial Function and PathologyCardiac Ischemia and Reperfusion

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Oxidation of a critical thiol residue of the adenine nucleotide translocator enforces Bcl-2-independent permeability transition pore opening and apoptosis

Costantini, Paola, Belzacq, Anne-Sophie, Vieira, Helena LA, Larochette, Nathanael, de Pablo, Manuel A, Zamzami, Naoufal, Susin, Santos A, Brenner, Catherine, Kroemer, Guido·2000·Oncogene
DOI 10.1038/sj.onc.1203299
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Abstract

Mitochondrial membrane permeabilization is a critical event in the process leading to physiological or chemotherapy-induced apoptosis. This permeabilization event is at least in part under the control of the permeability transition pore complex (PTPC), which interacts with oncoproteins from the Bcl-2 family as well as with tumor suppressor proteins from the Bax family, which inhibit or facilitate membrane permeabilization, respectively. Here we show that thiol crosslinking agents including diazenedicarboxylic acid bis 5N, N-dimethylamide (diamide), dithiodipyridine (DTDP), or bis-maleimido-hexane (BMH) can act on the adenine nucleotide translocator (ANT), one of the proteins within the PTPC. ANT alone reconstituted into artificial lipid bilayers suffices to confer a membrane permeabilization response to thiol crosslinking agents. Diamide, DTDP, and BMH but not tert-butylhydroperoxide or arsenite cause the oxidation of a critical cysteine residue (Cys 56) of ANT. Thiol modification within ANT is observed in intact cells, isolated mitochondria, and purified ANT. Recombinant Bcl-2 fails to prevent thiol modification of ANT. Concomitantly, a series of different thiol crosslinking agents (diamide, DTDP, and BMH, phenylarsine oxide) but not tert-butylhydroperoxide or arsenite induce mitochondrial membrane permeabilization and cell death irrespective of the expression level of Bcl-2. These data indicate that thiol crosslinkers cause a covalent modification of ANT which, beyond any control by Bcl-2, leads to mitochondrial membrane permeabilization and cell death.

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Crossref · 10.1038/sj.onc.1203299

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Research works printed but not linked: 2

  1. Brenner C, Cadiou H, Vieira HLA, Zamzami N, Marzo I, Xie Z, Leber B, Andrews D, Duclohier H, Reed JC and Kroemer G . 1999 Oncogene, in press.
  2. Susin SA, Larochette N, Geuskens M and Kroemer G . 1999a Meth Enzymol, in press.

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Metadata

Authors
Costantini, P., Belzacq, A.-S., Vieira, H. L., Larochette, N., de Pablo, M. A., Zamzami, N., Susin, S. A., Brenner, C., & Kroemer, G.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Université de Technologie de Compiègne (FR)
ORCID
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2000-01-13
Volume
19
Issue
2
Pages
307-314
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
DOI
10.1038/sj.onc.1203299
OpenAlex
W2053090763
Cited by
284
References
42
Citations by year
2026: 2 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 8 · 2017: 2 · 2016: 6 · 2015: 9 · 2014: 3 · 2013: 6 · 2012: 11
FWCI
9.41
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
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 › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
Keywords
adenine nucleotide translocase, mitochondrial permeability transition pore, mitochondrial membrane permeabilization, apoptosis, cysteine oxidation, Bcl-2, Bax, mitochondrial permeability transition, covalent modification, diamide, phenylarsine oxide, tert-butyl hydroperoxide, arsenite
MeSH terms
Mitochondrial ADP, ATP Translocases, Animals, Cell Line, Cross-Linking Reagents, Humans, Hybridomas, Intracellular Membranes, Oxidation-Reduction, Permeability, Sulfhydryl Compounds, Rats, Wistar, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Macromolecular Substances, Rats

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