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

https://doi.org/10.1006/abbi.2000.2066Get rights and content

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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    The bovine complex III was a kind gift of Dr. Neal Robinson. We are grateful to Drs. John J. Mieyal and Shadi Moghaddas for editorial review of the manuscript. We thank Mr. Steve Ingalls and Ms. Rachel Floyd for assistance with figure preparation. The technical assistance of Thomas Slabe, M.S., is greatly appreciated. These studies were supported by Grants 1RO1AG12447, 1RO1DK36069, 1K04AG00676, and 1POAG15885 from the National Institutes of Health and by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs.

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    To whom correspondence should be addressed at Cardiology Section, Medical Service 111(W), Louis Stokes VA Medical Center, 10701 East Boulevard, Cleveland, OH 44106. Fax: (216) 229-8509. E-mail: [email protected].

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