Lesnefsky E J, Gudz T I, Migita C T, Ikeda-Saito M, Hassan M O, Turkaly P J, Hoppel C L
Division of Cardiology, Case Western Reserve University, Cleveland, Ohio, USA.
Arch Biochem Biophys. 2001 Jan 1;385(1):117-28. doi: 10.1006/abbi.2000.2066.
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.
与成年心脏相比，衰老的心脏在缺血和再灌注过程中遭受的损伤更大。衰老会降低位于肌纤维之间的肌原纤维间线粒体（IFM）的氧化功能，而位于质膜下方的肌膜下线粒体（SSM）则保持不变。衰老通过改变细胞色素c结合位点，选择性地降低IFM中复合物III的活性。在整体缺血25分钟时，衰老心脏中SSM的复合物III活性降低，IFM中的复合物III活性进一步降低。缺血导致SSM和IFM中铁硫蛋白（ISP）的电子顺磁共振信号显著降低，尽管ISP肽的含量保持不变。因此，缺血导致ISP中铁硫中心的功能下降，而无亚基肽损失。在衰老的心脏中，再灌注开始时，IFM在通过复合物III的电子流路径中存在两个串联缺陷，这可能是氧化剂产生增加和再灌注损伤的机制。
