Ischemia-reperfusion injury in the aged heart: role of mitochondria.
The aged heart sustains greater injury during ischemia and reperfusion compared to the adult heart. Aging decreases oxidative phosphorylation and the activity of complexes III and IV only in interfibrillar mitochondria (IFM) that reside among the myofibrils, whereas subsarcolemmal mitochondria (SSM), located beneath the plasma membrane, remain unaltered. The peptide subunit composition of complexes III and IV is intact in aging. The aging defect in complex IV is in the inner membrane lipid environment. The defect in complex III is within the ubiquinol binding site of the cytochrome b subunit. Following ischemia, in the aged heart both SSM and IFM sustain additional decreases in complex III and complex IV activity. In contrast to the aging defect, with ischemia the subunits of complex IV appear to be damaged. Ischemia inactivates the iron-sulfur peptide subunit in complex III. Mitochondria are the major source of the reactive oxygen species that are generated during myocardial ischemia. Complex III is the major site of mitochondrial oxyradical production during ischemia in the adult heart. The role of complex III in the oxidative damage sustained by the aged heart during ischemia, as well as the potential contribution of aging defects in electron transport to ischemic damage in the aged heart, deserves further study. We propose that following ischemic damage to the electron transport chain, the production and release of reactive oxygen species increases from mitochondria in the aged heart, leading to additional damage during reperfusion.
Lesnefsky
Edward J
EJ
Department of Medicine, Division of Cardiology, Case Western Reserve University, Cleveland, OH 44106, USA.
Hoppel
Charles L
CL
D000367:Age Factors; D000818:Animals; D003573:Cytochrome b Group / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism
D003573:Cytochrome b Group; D003574:Cytochrome c Group; D007506:Iron-Sulfur Proteins; D017382:Reactive Oxygen Species; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III