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
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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In the citing paper
“it is known that modification of redox-sensitive thiols in this mitochondrial protein regulates the formation of the mitochondrial permeability transition (MPT) pore and cell death (101).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [101]
In the citing paper
“In contrast, the redox-sensitive thiols of ANT have been well studied as targets for modification by nitric oxide, peroxynitrite, thiol crosslinkers, and other thiol-reactive reagents (101, 435).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [101]
Citations
Cites
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Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked
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The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis
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Molecular characterization of mitochondrial apoptosis-inducing factor
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Self-citationBcl-2 functions in an antioxidant pathway to prevent apoptosis
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THE MITOCHONDRIAL DEATH/LIFE REGULATOR IN APOPTOSIS AND NECROSIS
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Self-citationBcl-2 inhibition of neural death: decreased generation of reactive oxygen species
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Self-citation
Research works printed but not linked: 2
- 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.
- Susin SA, Larochette N, Geuskens M and Kroemer G . 1999a Meth Enzymol, in press.
Cited by
Sorted by citations
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598
Self-citationTargeting mitochondria for cancer therapy
Fulda, S., Galluzzi, L., & Kroemer, G. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3137 · Cited by 1,678
Self-citationThe mitochondrion in apoptosis: how Pandora's box opens
Zamzami, N., & Kroemer, G. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35048073 · Cited by 1,055
Self-citationReactive Oxygen Species: A Breath of Life or Death?
Fruehauf, J. P., & Meyskens, F. L. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2082 · Cited by 921
Mitochondrial permeability transition and oxidative stress
Kowaltowski, A. J., Castilho, R. F., & Vercesi, A. E. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02316-x · Cited by 832
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)
- Venue
- Oncogene
- Published
- 2000-01-13
- Volume
- 19
- Issue
- 2
- Pages
- 307-314
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- 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
- 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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