Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg2+ Ions
| Autor: | Christoph Richter, Gonzalo Mazzei, Sylvie Montessuit, Astrid Osen-Sand, Rémy Sadoul, Jean-Claude Martinou, Bruno Antonsson, Anthony Nichols, Robert Eskes |
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| Rok vydání: | 1998 |
| Předmět: |
Cytochrome c Group
Mice Inbred Strains Mitochondria Liver Mitochondrion Transfection Permeability Mice cytochrome C Bcl-2-associated X protein Proto-Oncogene Proteins Cyclosporin a Animals Humans Cytochrome c oxidase Magnesium bcl-2-Associated X Protein biology Cytochrome c apoptosis Intracellular Membranes Cell Biology Recombinant Proteins Cell biology mitochondria Proto-Oncogene Proteins c-bcl-2 Mitochondrial permeability transition pore Bax Apoptosis COS Cells Cyclosporine biology.protein Female Apoptosome permeability transition Bongkrekic Acid Regular Articles HeLa Cells |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.143.1.217 |
| Popis: | Bcl-2 family members either promote or repress programmed cell death. Bax, a death-promoting member, is a pore-forming, mitochondria-associated protein whose mechanism of action is still unknown. During apoptosis, cytochrome C is released from the mitochondria into the cytosol where it binds to APAF-1, a mammalian homologue of Ced-4, and participates in the activation of caspases. The release of cytochrome C has been postulated to be a consequence of the opening of the mitochondrial permeability transition pore (PTP). We now report that Bax is sufficient to trigger the release of cytochrome C from isolated mitochondria. This pathway is distinct from the previously described calcium-inducible, cyclosporin A–sensitive PTP. Rather, the cytochrome C release induced by Bax is facilitated by Mg2+ and cannot be blocked by PTP inhibitors. These results strongly suggest the existence of two distinct mechanisms leading to cytochrome C release: one stimulated by calcium and inhibited by cyclosporin A, the other Bax dependent, Mg2+ sensitive but cyclosporin insensitive. |
| Databáze: | OpenAIRE |
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