Journal Article

Bid acts on the permeability transition pore complex to induce apoptosis

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

2000

Overview

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.

• Publisher: Nature Publishing,Nature Publishing Group,Nature Publishing Group [1987-....]
• Subject: Adenine / adenine nucleotide translocase / Ageing, cell death / Animals / Apoptosis / Bax protein / Bcl-2 protein / bcl-2-Associated X Protein / BH3 Interacting Domain Death Agonist Protein / BID protein / Biological and medical sciences / Bongkrekic Acid - pharmacology / Cancer / Carrier Proteins - genetics / Carrier Proteins - physiology / Cell death / Cell Line / Cell physiology / Cell-free system / Cells / Cyclosporin A / Cyclosporins - pharmacology / Cytoplasm / Electric Conductivity / Fundamental and applied biological sciences. Psychology / Genetic aspects / Health aspects / Intracellular Membranes - metabolism / Ion Channels / Life Sciences / Ligands / Lipid Bilayers - metabolism / Liposomes - metabolism / Membrane permeability / Membrane Proteins - drug effects / Membrane Proteins - metabolism / Membranes / Microinjection / Microinjections / Mitochondria / Mitochondria - drug effects / Mitochondria - metabolism / Mitochondrial ADP, ATP Translocases - metabolism / Mitochondrial DNA / Mitochondrial Membrane Transport Proteins / Mitochondrial permeability transition pore / Molecular and cellular biology / Permeability / Permeability - drug effects / permeability transition pore complex / Physiological aspects / Porins - metabolism / Proteins / Proto-Oncogene Proteins - metabolism / Proto-Oncogene Proteins c-bcl-2 / Rats / Recombinant Proteins - metabolism / Translocase