Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg2+ Ions
Open accessAbstract
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.
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MPT does not play a role in all forms of apoptosis.
“Formation of the pore can occur in response to many stimuli, including Ca2+ overload and oxidant stress, but MPT does not play a role in all forms of apoptosis (46, 125, 309, 438).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [125]
MPT pore formation can occur in response to many stimuli, including Ca2+ overload and oxidant stress.
“Formation of the pore can occur in response to many stimuli, including Ca2+ overload and oxidant stress, but MPT does not play a role in all forms of apoptosis (46, 125, 309, 438).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [125]
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- Authors
- Eskes, R., Antonsson, B., Osen-Sand, A., Montessuit, S., Richter, C., Sadoul, R., Mazzei, G., Nichols, A., & Martinou, J.-C.
- Affiliations
- ETH Zurich (CH)
- *Serono Pharmaceutical Research Institute, 1228 Plan-les-Ouates, Geneva, Switzerland; and ‡ ETH Laboratory of Biochemistry, 8092 Zurich, Switzerland
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 1998-10-05
- Volume
- 143
- Issue
- 1
- Pages
- 217-224
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2132823
- OpenAlex
- W2052793452
- Cited by
- 651
- References
- 41
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 7 · 2020: 10 · 2019: 14 · 2018: 15 · 2017: 10 · 2016: 10 · 2015: 14 · 2014: 12 · 2013: 15 · 2012: 14
- FWCI
- 21.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- Bax, cytochrome c release, mitochondrial permeability transition pore, magnesium ions, apoptosis, Bcl-2 family proteins, cyclosporine, calcium, Apaf-1, caspase activation, mitochondrial outer membrane
- MeSH terms
- Animals, Bongkrekic Acid, Cytochrome c Group, Female, HeLa Cells, Humans, Intracellular Membranes, Magnesium, Mice, Inbred Strains, Mitochondria, Liver, Permeability, Proto-Oncogene Proteins, Recombinant Proteins, Transfection, Cyclosporine, Proto-Oncogene Proteins c-bcl-2, COS Cells, bcl-2-Associated X Protein, Mice
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