Hoppel Charles L, Moghaddas Shadi, Lesnefsky Edward J
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Biogerontology. 2002;3(1-2):41-4. doi: 10.1023/a:1015251212039.
We used the Fischer 344 rat as a model for aging effects on the heart. Cardiac interfibrillar mitochondria (IFM), located between the myofibrils, exhibit a decrease in protein yield and oxidative phosphorylation through complex III and IV in elderly (24 months) compared to adult controls (6 months). In contrast, subsarcolemmal mitochondria (SSM) located beneath the plasma membrane remained unchanged. The activity of electron transport complex III decreased only in the IFM with aging. Complex III and IV require an inner mitochondrial membrane lipid, cardiolipin for maximal activity. However, the content and composition of cardiolipin was unchanged in the IFM from aging hearts. We observed electron leakage in complex III at the myxothiazol site in the aging IFM accompanied by increased superoxide production. The aging heart sustains greater injury during ischemia and reperfusion compared to adult hearts. We propose that ischemic damage combines with aging defects in complex III to increase oxidative injury in aging hearts. Ischemia damaged complex III in both SSM and IFM from adult and aging hearts via impairment of the iron-sulfur subunit without the loss of the apoprotein. Thus, at the onset of reperfusion, complex III in IFM contains two defects in electron flow, which are likely to prime complex III for enhanced oxidant production during reperfusion, leading to increased damage in aging hearts.
我们使用Fischer 344大鼠作为研究衰老对心脏影响的模型。位于肌原纤维之间的心肌纤维间线粒体（IFM），与成年对照组（6个月）相比，老年（24个月）大鼠的IFM通过复合体III和IV的蛋白质产量及氧化磷酸化降低。相比之下，位于质膜下方的肌膜下线粒体（SSM）则保持不变。电子传递复合体III的活性仅在IFM中随衰老而降低。复合体III和IV需要线粒体内膜脂质心磷脂才能发挥最大活性。然而，衰老心脏的IFM中心磷脂的含量和组成并未改变。我们观察到衰老的IFM中在抗霉素A位点的复合体III存在电子泄漏，并伴有超氧化物生成增加。与成年心脏相比，衰老心脏在缺血和再灌注期间承受更大的损伤。我们提出，缺血损伤与复合体III中的衰老缺陷相结合，会增加衰老心脏的氧化损伤。缺血通过铁硫亚基的损伤使成年和衰老心脏的SSM和IFM中的复合体III受损，但脱辅基蛋白并未丢失。因此，在再灌注开始时，IFM中的复合体III在电子流方面存在两个缺陷，这可能会使复合体III在再灌注期间产生更多氧化剂，导致衰老心脏损伤增加。
