Cited by 1,225Cell death mechanisms and regulationMitochondrial Function and PathologyAutophagy in Disease and Therapy

Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD‐specific caspase activation and independently of mitochondrial transmembrane depolarization

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Bossy‐Wetzel, Ella, Newmeyer, Donald D., Green, Douglas R.·1998·The EMBO Journal

Abstract

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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Crossref · 10.1093/emboj/17.1.37

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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.
Venue
The EMBO Journal
Published
1998-01-01
Volume
17
Issue
1
Pages
37-49
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
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
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

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