Cited by 160Cardiac Ischemia and ReperfusionMitochondrial Function and PathologyAutophagy in Disease and Therapy

Ischemic Injury to Mitochondrial Electron Transport in the Aging Heart: Damage to the Iron–Sulfur Protein Subunit of Electron Transport Complex III

Lesnefsky, Edward J., Gudz, Tatyana I., Migita, Catharina T., Ikeda-Saito, Masao, Hassan, Medhat O., Turkaly, Peter J., Hoppel, Charles L.·2001·Archives of Biochemistry and Biophysics

Abstract

The aging heart sustains greater injury during ischemia and reperfusion compared to adult hearts. Aging decreases oxidative function in interfibrillar mitochondria (IFM) that reside among the myofibers, while subsarcolemmal mitochondria (SSM), located beneath the plasma membrane, remain unaltered. Aging decreases complex III activity selectively in IFM via alteration of the cytochrome c binding site. With 25 min of global ischemia, complex III activity decreases in SSM and further decreases in IFM in the aging heart. Ischemia leads to a marked decrease in the electron paramagnetic resonance signal of the iron-sulfur protein (ISP) in both SSM and IFM, despite a preserved content of ISP peptide. Thus, ischemia results in a functional decrease in the iron-sulfur center in ISP without subunit peptide loss. In the aging heart, at the onset of reperfusion, IFM contain two tandem defects in the path of electron flow through complex III, providing a likely mechanism for enhanced oxidant production and reperfusion damage.

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Crossref · 10.1006/abbi.2000.2066

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Authors
Lesnefsky, E. J., Gudz, T. I., Migita, C. T., Ikeda-Saito, M., Hassan, M. O., Turkaly, P. J., & Hoppel, C. L.
Affiliations
  • Louis Stokes Cleveland VA Medical Center (US)
  • Yamaguchi University (JP)
Corresponding author
Lesnefsky, Edward J.
Venue
Archives of Biochemistry and Biophysics
Publisher
Elsevier BV
Published
2001-01
Volume
385
Issue
1
Pages
117-128
ISSN
0003-9861 (ISSN-L)
OpenAlex
W2074154058
Cited by
160
References
47
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 14 · 2016: 6 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 14
FWCI
4.16
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of Biochemistry and Biophysics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ag012447-06, 5k04ag000676-05, 5r01dk036069-08)
  • Substance Abuse and Mental Health Services Administration (1POAG15885)
  • National Institute on Aging (1RO1AG12447, 1K04 AG-00676)
  • National Institute of Diabetes and Digestive and Kidney Diseases (1RO1DK36069)
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
cardiac aging, myocardial ischemia, ischemia-reperfusion injury, mitochondrial electron transport chain, cytochrome bc1 complex, iron-sulfur proteins, interfibrillar mitochondria, subsarcolemmal mitochondria, iron-sulfur clusters, oxidative stress, oxidant production
MeSH terms
Age Factors, Aging, Animals, Binding Sites, Cell Membrane, Cytochrome c Group, Electron Transport Complex IV, Electron Spin Resonance Spectroscopy, Electron Transport, Electrophoresis, Polyacrylamide Gel, Iron, Ischemia, Male, Mitochondria, Myocardium, Oxygen, Rats, Inbred F344, Sarcolemma, Sulfur, Immunoblotting, Reperfusion Injury, Reactive Oxygen Species, Rats

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