Interaction of peroxidized cardiolipin with rat‐heart mitochondrial membranes: Induction of permeability transition and cytochrome c release
Abstract
Cardiolipin peroxidation plays a critical role in mitochondrial cytochrome c release and subsequent apoptotic process. Mitochondrial pore transition (MPT) is considered as an important step in this process. In this work, the effect of peroxidized cardiolipin on MPT induction and cytochrome c release in rat heart mitochondria was investigated. Treatment of mitochondria with micromolar concentrations of cardiolipin hydroperoxide (CLOOH) resulted in a dose‐dependent matrix swelling, Δ Ψ collapse, release of preaccumulated Ca 2+ and release of cytochrome c . All these events were inhibited by cyclosporin A and bongkrekic acid, indicating that peroxidized cardiolipin behaves as an inducer of MPT. Ca 2+ accumulation by mitochondria was required for this effect. ANT (ADP/ATP translocator) appears to be involved in the CLOOH‐dependent MPT induction, as suggested by the modulation by ligands and inhibitors of adenine nucleotide translocator (ANT). Together, these results indicate that peroxidized cardiolipin lowers the threshold of Ca 2+ for MPT induction and cytochrome c release. This synergistic effect of Ca 2+ and peroxidized cardiolipin on MPT induction and cytochrome c release in mitochondria, might be important in regulating the initial phase of apoptosis and also may have important implications in those physiopathological situations, characterized by both Ca 2+ and peroxidized cardiolipin accumulation in mitochondria, such as aging, ischemia/reperfusion and other degenerative diseases.
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ROS trigger or mediate ischemic and pharmacologic preconditioning of hearts.
“It is now well known that ROS trigger or mediate ischemic and pharmacologic preconditioning of hearts (15, 27, 102, 181, 183, 248, 254, 303).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [254]
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- Authors
- Petrosillo, G., Casanova, G., Matera, M., Ruggiero, F. M., & Paradies, G.
- Affiliations
- Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IT)
- Corresponding author
- Paradies, Giuseppe
- ORCID
- Petrosillo, Giuseppe
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2006-10-27
- Volume
- 580
- Issue
- 27
- Pages
- 6311-6316
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2004428815
- Cited by
- 137
- References
- 37
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 11 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 6 · 2013: 7 · 2012: 6
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- 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 › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- cardiolipin peroxidation, mitochondrial permeability transition, cytochrome c release, heart mitochondria, calcium accumulation, adenine nucleotide translocase, cyclosporine, bongkrekic acid, mitochondrial membrane potential, apoptosis, ischemia-reperfusion
- MeSH terms
- Mitochondrial ADP, ATP Translocases, Aging, Animals, Calcium, Cardiolipins, Cell Membrane Permeability, Dose-Response Relationship, Drug, Ischemia, Mitochondria, Heart, Lipid Peroxidation, Apoptosis, Cytochromes c, Rats
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