Cited by 178Cell death mechanisms and regulationMitochondrial Function and PathologyCardiac Ischemia and Reperfusion

Bid acts on the permeability transition pore complex to induce apoptosis

Zamzami, Naoufal, Hamel, Chahrazed El, Maisse, Carine, Brenner, Catherine, Muñoz-Pinedo, Cristina, Belzacq, Anne-Sophie, Costantini, Paola, Vieira, Helena +3 more·2000·Oncogene

Abstract

Similar to most if not all pro-apoptotic members of the Bcl-2 family, Bid (and its truncated product t-Bid) triggers cell death via mitochondrial membrane permeabilization (MMP). This effect can be monitored in intact cells, upon microinjection of recombinant Bid protein into the cytoplasm, as well as in purified mitochondria, upon addition of Bid protein. Here we show that Bid-induced MMP can be inhibited, both in cells and in the cell-free system, by three pharmacological inhibitors of the permeability transition pore complex (PTPC), namely cyclosporin A, N-methyl-4-Val-cyclosporin A, and bongkrekic acid (a ligand of the adenine nucleotide translocase, ANT, one of the PTPC components). Bid effects on synthetic membranes were studied either in proteoliposomes or in synthetic bilayers subjected to electrophysiological measurements. Full length Bid preferentially permeabilizes membranes and induces the formation of large conductance channels at neutral pH, when added to liposomes or bilayers containing both purified ANT and Bax, yet has no or little effect combined with ANT or Bax alone. t-Bid acts on membranes containing ANT alone with the same efficiency as on those containing both ANT and Bax. These results suggest that the proapoptotic effects of Bid are mediated, at least in part, by its functional interaction with ANT, one of the major components of PTPC.

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Crossref · 10.1038/sj.onc.1204030

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Authors
Zamzami, N., Hamel, C. E., Maisse, C., Brenner, C., Muñoz-Pinedo, C., Belzacq, A.-S., Costantini, P., Vieira, H., Loeffler, M., Molle, G., & Kroemer, G.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Université de Technologie de Compiègne (FR)
Venue
Oncogene
Published
2000-12-14
Volume
19
Issue
54
Pages
6342-6350
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
OpenAlex
W2000834350
Cited by
178
References
52
Citations by year
2025: 3 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 7
FWCI
5.90
Type
journal article
Language
en
Open access
closed
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
Funders
Ligue Contre le Cancer
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
Bid, apoptosis, mitochondrial membrane permeabilization, cyclosporine, bongkrekic acid, adenine nucleotide translocase, Bax, Bcl-2 family proteins, membrane permeabilization, proteoliposomes
MeSH terms
Mitochondrial Permeability Transition Pore, Mitochondrial ADP, ATP Translocases, Animals, Bongkrekic Acid, Carrier Proteins, Cell Line, Cyclosporins, Electric Conductivity, Intracellular Membranes, Ion Channels, Lipid Bilayers, Liposomes, Membrane Proteins, Microinjections, Mitochondria, Permeability, Proto-Oncogene Proteins, Recombinant Proteins, Apoptosis, Porins, Proto-Oncogene Proteins c-bcl-2, Mitochondrial Membrane Transport Proteins, BH3 Interacting Domain Death Agonist Protein, bcl-2-Associated X Protein, Rats

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