Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD‐specific caspase activation and independently of mitochondrial transmembrane depolarization
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Mitochondrial cytochrome c, which functions as an electron carrier in the respiratory chain, translocates to the cytosol in cells undergoing apoptosis, where it participates in the activation of DEVD-specific caspases. The apoptosis inhibitors Bcl-2 or Bcl-xL prevent the efflux of cytochrome c from mitochondria. The mechanism responsible for the release of cytochrome c from mitochondria during apoptosis is unknown. Here, we report that cytochrome c release from mitochondria is an early event in the apoptotic process induced by UVB irradiation or staurosporine treatment in CEM or HeLa cells, preceding or at the time of DEVD-specific caspase activation and substrate cleavage. A reduction in mitochondrial transmembrane potential (Deltapsim) occurred considerably later than cytochrome c translocation and caspase activation, and was not necessary for DNA fragmentation. Although zVAD-fmk substantially blocked caspase activity, a reduction in Deltapsim and cell death, it failed to prevent the passage of cytochrome c from mitochondria to the cytosol. Thus the translocation of cytochrome c from mitochondria to cytosol does not require a mitochondrial transmembrane depolarization.
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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 [46]
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 [46]
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- Authors
- Bossy‐Wetzel, E., Newmeyer, D. D., & Green, D. R.
- Affiliations
- La Jolla Institute for Immunology (US)
- Corresponding author
- Bossy‐Wetzel, Ella
- Green, Douglas R.
- ORCID
- Green, Douglas R.
- Venue
- The EMBO Journal
- Published
- 1998-01-01
- Volume
- 17
- Issue
- 1
- Pages
- 37-49
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170356
- OpenAlex
- W2072858020
- Cited by
- 1,225
- References
- 111
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 7 · 2023: 10 · 2022: 11 · 2021: 19 · 2020: 11 · 2019: 8 · 2018: 13 · 2017: 14 · 2016: 12 · 2015: 14 · 2014: 20 · 2013: 26 · 2012: 26
- FWCI
- 57.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- American Cancer Society
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health (CA-69381)
- National Cancer Institute (CA 69381, P01CA069381)
- National Institute of General Medical Sciences (GM50284, R01GM050284, GM-52735)
- 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
- cytochrome c release, apoptosis, caspase activation, mitochondrial membrane potential, mitochondrial depolarization, Bcl-2, Bcl-xL, z-VAD-fmk, staurosporine, UVB irradiation, DNA fragmentation, CCRF-CEM cells, HeLa cells
- MeSH terms
- Amino Acid Chloromethyl Ketones, Biological Transport, Cell Line, Cysteine Endopeptidases, Cytochrome c Group, Cytosol, Enzyme Activation, Humans, Membrane Potentials, Mitochondria, Oligopeptides, Tumor Cells, Cultured, Ultraviolet Rays, Cysteine Proteinase Inhibitors, Apoptosis, Staurosporine, DNA Fragmentation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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