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 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.
Lesnefsky
E J
EJ
Division of Cardiology, Case Western Reserve University, Cleveland, Ohio, USA. ex19@po.cwru.edu
Gudz
T I
TI
Migita
C T
CT
Ikeda-Saito
M
M
Hassan
M O
MO
Turkaly
P J
PJ
Hoppel
C L
CL
D000367:Age Factors; D000375:Aging; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003574:Cytochrome c Group / Q000737:chemistry / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D007501:Iron / Q000737:chemistry*; D007511:Ischemia; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism / Q000648:ultrastructure; D013455:Sulfur / Q000737:chemistry*
D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; D013455:Sulfur; D007501:Iron; D003576:Electron Transport Complex IV; D010100:Oxygen