Ischemic injury to mitochondrial electron transport in the aging heart: Damage to the iron-sulfur protein subunit of electron transport complex III

The aging heart sustains greater injury during ischemia and reperfusion com pared to adult hearts, Aging decreases oxidative function in interfibrillar mitochondria (IFM) that reside among the myofibers, while subsarcolemmal m itochondria (SSM), located beneath the plasma membrane, remain unaltered. A ging decreases complex III activity selectively in IFM via alteration of th e cytochrome c binding site. With 25 min of global ischemia, complex III ac tivity decreases in SSM and further decreases in IFM in the aging heart. Is chemia leads to a marked decrease in the electron paramagnetic resonance si gnal of the iron-sulfur protein (ISP) in both SSM and IFM, despite a preser ved content of ISP peptide. Thus, ischemia results in a functional decrease in the iron-sulfur center in ISP without subunit peptide loss. In the agin g heart, at the onset of reperfusion, IFM contain two tandem defects in the path of electron flow through complex III, providing a likely mechanism fo r enhanced oxidant production and reperfusion damage. (C) 2001 Academic Pre ss.