Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis
Open accessAbstract
During apoptosis, the permeabilization of the mitochondrial outer membrane allows the release of cytochrome c, which induces caspase activation to orchestrate the death of the cell. Mitochondria rapidly lose their transmembrane potential (ΔΨm) and generate reactive oxygen species (ROS), both of which are likely to contribute to the dismantling of the cell. Here we show that both the rapid loss of ΔΨm and the generation of ROS are due to the effects of activated caspases on mitochondrial electron transport complexes I and II. Caspase-3 disrupts oxygen consumption induced by complex I and II substrates but not that induced by electron transfer to complex IV. Similarly, ΔΨm generated in the presence of complex I or II substrates is disrupted by caspase-3, and ROS are produced. Complex III activity measured by cytochrome c reduction remains intact after caspase-3 treatment. In apoptotic cells, electron transport and oxygen consumption that depends on complex I or II was disrupted in a caspase-dependent manner. Our results indicate that after cytochrome c release the activation of caspases feeds back on the permeabilized mitochondria to damage mitochondrial function (loss of ΔΨm) and generate ROS through effects of caspases on complex I and II in the electron transport chain.
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Cardiolipin can be especially damaged by ROS because of its important roles.
“Cardiolipin can be especially damaged by ROS because of these important roles (213, 258, 260, 261).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [261]
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- Authors
- Ricci, J.-E., Gottlieb, R. A., & Green, D. R.
- Affiliations
- La Jolla Institute for Immunology (US)
- Scripps Research Institute (US)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2003-01-06
- Volume
- 160
- Issue
- 1
- Pages
- 65-75
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2172744
- OpenAlex
- W2158720649
- Cited by
- 504
- References
- 46
- Citations by year
- 2026: 18 · 2025: 18 · 2024: 15 · 2023: 7 · 2022: 16 · 2021: 17 · 2020: 11 · 2019: 14 · 2018: 15 · 2017: 17 · 2016: 17 · 2015: 25 · 2014: 26 · 2013: 10 · 2012: 20
- FWCI
- 15.40
- 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)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 69381, P01CA069381)
- National Institute of Allergy and Infectious Diseases (R01AI040646, AI40646)
- 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
- apoptosis, caspase-3, mitochondrial permeability transition, mitochondrial membrane potential, reactive oxygen species, cytochrome c release, mitochondrial electron transport chain, complex I, complex II, cytochrome bc1 complex, oxygen consumption, mitochondrial dysfunction
- MeSH terms
- Amino Acid Chloromethyl Ketones, Cytochrome c Group, Dactinomycin, Dose-Response Relationship, Drug, Electron Transport, HeLa Cells, Humans, Membrane Potentials, Mitochondria, Models, Biological, Oxygen, Oxygen Consumption, Protein Synthesis Inhibitors, Recombinant Proteins, Ultraviolet Rays, Blotting, Western, Apoptosis, Reactive Oxygen Species, Caspases, Caspase 3
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