Bid acts on the permeability transition pore complex to induce apoptosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-12

AUTHORS

Naoufal Zamzami, Chahrazed El Hamel, Carine Maisse, Catherine Brenner, Cristina Muñoz-Pinedo, Anne-Sophie Belzacq, Paola Costantini, Helena Vieira, Markus Loeffler, Gérard Molle, Guido Kroemer

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. More... »

PAGES

1204030

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1204030

DOI

http://dx.doi.org/10.1038/sj.onc.1204030

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040534800

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11175349


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