Bid acts on the permeability transition pore complex to induce apoptosis
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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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 [410]
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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)
- ORCID
- 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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