The Mitochondrial Permeability Transition, Release of Cytochrome c and Cell Death
Open accessAbstract
We investigated the relationship between opening of the permeability transition pore (PTP), mitochondrial depolarization, cytochrome c release, and occurrence of cell death in rat hepatoma MH1C1 cells. Treatment with arachidonic acid or induces PTP opening in situ with similar kinetics, as assessed by the calcein loading-Co(2+) quenching technique (Petronilli, V., Miotto, G., Canton, M., Colonna, R., Bernardi, P., and Di Lisa, F. (1999) Biophys. J. 76, 725-734). Yet depolarization, as assessed from the changes of mitochondrial tetramethylrhodamine methyl ester (TMRM) fluorescence, is rapid and extensive with arachidonic acid and slow and partial with. Cyclosporin A-inhibitable release of cytochrome c and cell death correlate with the changes of TMRM fluorescence but not with those of calcein fluorescence. Since pore opening must be accompanied by depolarization, we conclude that short PTP openings are detected only by trapped calcein and may have little impact on cell viability, while changes of TMRM distribution require longer PTP openings, which cause release of cytochrome c and may result in cell death. Modulation of the open time appears to be the key element in determining the outcome of stimuli that converge on the PTP.
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Oxidative stress-dependent cell death largely depends on the activation of mPTP.
“Oxidative stress-dependent cell death largely depends on the activation of mPTP.”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [4]
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- Authors
- Petronilli, V., Penzo, D., Scorrano, L., Bernardi, P., & Di Lisa, F.
- Affiliations
- University of Padua (IT)
- Corresponding author
- Petronilli, Valeria
- Bernardi, Paolo
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 276
- Issue
- 15
- Pages
- 12030-12034
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1976348423
- Cited by
- 472
- References
- 43
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 11 · 2023: 10 · 2022: 7 · 2021: 16 · 2020: 23 · 2019: 10 · 2018: 20 · 2017: 16 · 2016: 17 · 2015: 15 · 2014: 29 · 2013: 18 · 2012: 19
- FWCI
- 10.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial permeability transition, mitochondrial permeability transition pore, cytochrome c release, mitochondrial depolarization, cell death, arachidonic acid, cyclosporine, hepatoma cells, calcein fluorescence
- MeSH terms
- Calcimycin, Animals, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Cell Membrane Permeability, Cytochrome c Group, Liver Neoplasms, Experimental, Mitochondria, Liver, Tumor Cells, Cultured, Arachidonic Acid, Apoptosis, Rats
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