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BID-dependent and BID-independent pathways for BAX insertion into mitochondria
BID-dependent and BID-independent pathways for BAX insertion into mitochondria
5394
In the absence of an apoptotic signal, BAX adopts a conformation that constrains the protein from integrating into mitochondrial membranes. Here, we show that caspases, including caspase-8, can initiate BAX insertion into mitochondria in vivo and in vitro. The cleavage product of caspase-8, tBID, induced insertion of BAX into mitochondria in vivo, and reconstitution in vitro showed that tBID, either directly or indirectly, relieved inhibition of the BAX transmembrane signal-anchor by the NH2-terminal domain, resulting in integration of BAX into mitochondrial membrane. In contrast to these findings, however, Bid-null mouse embryo fibroblasts supported Bax insertion into mitochondria in response to death signaling by either TNFalpha or E1A, despite the fact that cytochrome c release from the organelle was inhibited. We conclude, therefore, that a parallel Bid-independent pathway exists in these cells for mitochondrial insertion of Bax and that, in the absence of Bid, cytochrome c release can be uncoupled from Bax membrane insertion.
Ruffolo SC, Breckenridge DG, Nguyen M, Goping IS, Gross A, Korsmeyer SJ, Li H, Yuan J, Shore GC
Cell death and differentiation
2000-11-01 00:00
7
11
1101-8
Amino Acid Chloromethyl Ketones,Animals,Antigens, CD95,BH3 Interacting Domain Death Agonist Protein,Carrier Proteins,Caspases,Cells, Cultured,Cytochrome c Group,Electron Transport Complex IV,Enzyme Inhibitors,Epithelial Cells,Fibroblasts,Humans,Intracellular Membranes,Mice,Microscopy, Confocal,Mitochondria, Heart,Protein Structure, Tertiary,Proto-Oncogene Proteins,Proto-Oncogene Proteins c-bcl-2,Rats,Signal Transduction,bcl-2-Associated X Protein,Amino Acid Chloromethyl Ketones,Antigens, CD95,BAX protein, human,BH3 Interacting Domain Death Agonist Protein,BID protein, human,Bax protein, mouse,Bax protein, rat,Bid protein, mouse,Bid protein, rat,Carrier Proteins,Cytochrome c Group,Enzyme Inhibitors,Proto-Oncogene Proteins,Proto-Oncogene Proteins c-bcl-2,bcl-2-Associated X Protein,benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone,Electron Transport Complex IV,Caspases
Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Cell Death Differ.
1350-9047
10.1038/sj.cdd.4400739
0
False
11139284
