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Cited by 468Cardiac Ischemia and ReperfusionMitochondrial Function and PathologyCell death mechanisms and regulation

Decrease in Mitochondrial Complex I Activity in Ischemic/Reperfused Rat Heart: Involvement of Reactive Oxygen Species and Cardiolipin

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Paradies, Giuseppe, Petrosillo, Giuseppe, Pistolese, Marilva, Di Venosa, Nicola, Federici, Antonio, Ruggiero, Francesca Maria·2004·Circulation Research
DOI 10.1161/01.res.0000109416.56608.64
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Abstract

Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocytes. Mitochondrial respiration is an important source of ROS production and hence a potential contributor to cardiac reperfusion injury. In this study, we have examined the effect of ischemia and ischemia followed by reperfusion of rat hearts on various parameters related to mitochondrial function, such as complex I activity, oxygen consumption, ROS production, and cardiolipin content. The activity of complex I was reduced by 25% and 48% in mitochondria isolated from ischemic and reperfused rat heart, respectively, compared with the controls. These changes in complex I activity were associated with parallel changes in state 3 respiration. The capacity of mitochondria to produce H 2 O 2 increased on reperfusion. The mitochondrial content of cardiolipin, which is required for optimal activity of complex I, decreased by 28% and 50% as function of ischemia and reperfusion, respectively. The lower complex I activity in mitochondria from reperfused rat heart could be completely restored to the level of normal heart by exogenous added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids nor by peroxidized cardiolipin. It is proposed that the defect in complex I activity in ischemic/reperfused rat heart could be ascribed to a ROS-induced cardiolipin damage. These findings may provide an explanation for some of the factors responsible for myocardial reperfusion injury.

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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 [5]

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  • One or more Fe-S centers is a likely source of O2•− within complex I, although the ubisemiquinone binding site or the flavin complex could also be sources.

    “One or more of the Fe-S centers is a likely source (135, 160, 251), although the ubisemiquinone (QH•) binding site (143, 160, 200), or the flavin complex (216), per se, could also be sources”

    From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [251]

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Authors
Paradies, G., Petrosillo, G., Pistolese, M., Di Venosa, N., Federici, A., & Ruggiero, F. M.
Affiliations
  • Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IT)
  • From the Department of Biochemistry and Molecular Biology and CNR Institute of Biomembranes and Bioenergetics (G. Paradies, G. Petrosillo, M.P., F.M.R.), Department of Emergency and Transplantation (N.D.V.), and Department of Pharmacology and Human Physiology (A.F.), University of Bari, Italy.
ORCID
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2004-01-09
Volume
94
Issue
1
Pages
53-59
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/01.res.0000109416.56608.64
OpenAlex
W2142397871
Cited by
468
References
6
Citations by year
2026: 12 · 2025: 19 · 2024: 22 · 2023: 25 · 2022: 19 · 2021: 21 · 2020: 14 · 2019: 23 · 2018: 17 · 2017: 28 · 2016: 20 · 2015: 20 · 2014: 21 · 2013: 25 · 2012: 33
FWCI
8.30
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
  • Zenodo (CERN European Organization for Nuclear Research) (other-oa)
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
mitochondrial complex I, myocardial ischemia-reperfusion injury, reactive oxygen species, cardiolipin, hydrogen peroxide production, state 3 respiration, mitochondrial oxygen consumption, cardiolipin peroxidation, phospholipids, heart mitochondria
MeSH terms
Animals, Cardiolipins, Male, Mitochondria, Heart, Myocardium, Organ Culture Techniques, Oxygen Consumption, Myocardial Reperfusion Injury, Rats, Wistar, Reactive Oxygen Species, Cell Respiration, Electron Transport Complex I, Rats

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