BID-dependent and BID-independent pathways for BAX insertion into mitochondria
| Autor: | Stanley J. Korsmeyer, Honglin Li, A. Gross, Junying Yuan, D. G. Breckenridge, Ing Swie Goping, Gordon C. Shore, Minh Dang Nguyen, S. C. Ruffolo |
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| Rok vydání: | 2001 |
| Předmět: |
Cytochrome c Group
Mitochondrion Mitochondria Heart Amino Acid Chloromethyl Ketones Electron Transport Complex IV Mice Bcl-2-associated X protein Proto-Oncogene Proteins Animals Humans fas Receptor Enzyme Inhibitors Inner mitochondrial membrane Molecular Biology Caspase Heart metabolism Cells Cultured bcl-2-Associated X Protein Microscopy Confocal biology Chemistry Cytochrome c Epithelial Cells Cell Biology Intracellular Membranes Fibroblasts Transmembrane protein Cell biology Protein Structure Tertiary Rats Proto-Oncogene Proteins c-bcl-2 Apoptosis Caspases biology.protein Carrier Proteins BH3 Interacting Domain Death Agonist Protein Signal Transduction |
| Zdroj: | Cell death and differentiation. 7(11) |
| ISSN: | 1350-9047 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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