Decreased complex III activity in mitochondria isolated from rat heart subjected to ischemia and reperfusion: role of reactive oxygen species and cardiolipin
Abstract
Reactive oxygen species (ROS) are considered an important factor in ischemia‐reperfusion injury to cardiac myocites. We have examined the effects of ischemia (30 min) and ischemia followed by reperfusion (15 min) of rat hearts on the activity of complex III and on the cardiolipin content in isolated mitochondria. Mitochondrial production of H 2 O 2 and lipid peroxidation was also measured. The capacity of mitochondria to produce both H 2 O 2 and lipid peroxidation increased upon reperfusion. The activity of complex III was 22% and 46% lower in ischemic and reperfused rat heart mitochondria, respectively, than that of controls. These changes in complex III activity were associated to parallel changes in state 3 respiration. The mitochondrial content of cardiolipin, which is required for optimal activity of complex III, decreased by 28% and by 50% as a function of ischemia and reperfusion, respectively. The lower complex III activity in mitochondria from reperfused rat hearts could be completely restored to the level of normal hearts by exogenously added cardiolipin. It is proposed that the loss of complex III activity in reperfused rat hearts can be mainly ascribed to a loss of cardiolipin content, due to oxidative attack by oxygen free radicals.
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Peroxidation of mitochondrial phospholipids may affect the integrity of permeability transition pores and disaggregate complexes I and III of the respiratory chain, thereby enhancing electron leakage within the mitochondrial intermembrane space.
“peroxidation of mitochondrial phospholipids may affect the integrity of permeability transition pores (PTPs) and disaggregate complexes I and III of the respiratory chain, thereby enhancing electron leakage within the mitochondrial intermembrane space5,6.”
From ROS in cancer therapy: the bright side of the moon (2020) · cites this paper as [6]
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- Authors
- Petrosillo, G., Francesca, M. R., Di Venosa, N., & Paradies, A. G.
- Affiliations
- University of Bari Aldo Moro (IT)
- Department of Emergency and Transplantation University of Bari Bari Italy
- Department of Biochemistry and Molecular Biology CNR Unit for the Study of Mitochondria and Bioenergetics University of Bari Bari Italy
- ORCID
- Petrosillo, Giuseppe
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2003-02-05
- Volume
- 17
- Issue
- 6
- Pages
- 714-716
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2158719453
- Cited by
- 261
- References
- 50
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 5 · 2022: 11 · 2021: 9 · 2020: 7 · 2019: 11 · 2018: 9 · 2017: 12 · 2016: 13 · 2015: 13 · 2014: 10 · 2013: 14 · 2012: 17
- FWCI
- 7.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Consiglio Nazionale delle Ricerche
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- cytochrome bc1 complex, mitochondrial respiratory chain, ischemia-reperfusion injury, cardiolipin, reactive oxygen species, hydrogen peroxide, lipid peroxidation, state 3 respiration, heart mitochondria, oxidative damage
- MeSH terms
- Animals, Cardiolipins, Hydrogen Peroxide, Mitochondria, Heart, Phospholipids, Electron Transport Complex III, Myocardial Reperfusion Injury, Myocardial Ischemia, Reactive Oxygen Species, Rats
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