Fannin S W, Lesnefsky E J, Slabe T J, Hassan M O, Hoppel C L
Department of Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
Arch Biochem Biophys. 1999 Dec 15;372(2):399-407. doi: 10.1006/abbi.1999.1508.
Mitochondrial-derived oxidative injury contributes to cellular aging as well as to reperfusion-induced tissue damage. While the aging-heart suffers greater tissue damage following ischemia and reperfusion than the adult heart, the occurrence of aging-related alterations in mitochondrial oxidative metabolism in the elderly heart has remained uncertain. We determined if aging altered oxidative metabolism in either of the two populations of cardiac mitochondria, subsarcolemmal mitochondria (SSM) that reside beneath the plasma membrane or interfibrillar mitochondria (IFM) located between the myofibrils. SSM and IFM were isolated from 6-month adult and 24- and 28-month elderly Fischer 344 rat hearts. Aging-related alterations were limited to IFM, while SSM remained unaffected. Aging decreased the rate of oxidative phosphorylation in IFM, including when stimulated by electron donors specific for cytochrome oxidase. Cytochrome oxidase enzyme activity was decreased in IFM from aging hearts, while activity in SSM remained similar to adult controls. These findings allow future studies of aging-related decrements in oxidative function to focus upon IFM, while SSM provide an inherent control group of mitochondria that are free of aging-related alterations in oxidative function. The selective alteration of IFM during aging raises the possibility that the consequences of aging-induced mitochondrial dysfunction will be enhanced in specific subcellular regions of the senescent myocyte.
线粒体衍生的氧化损伤会导致细胞衰老以及再灌注诱导的组织损伤。虽然衰老心脏在缺血和再灌注后比成年心脏遭受更大的组织损伤，但老年心脏中线粒体氧化代谢中与衰老相关的改变是否存在仍不确定。我们确定衰老是否改变了心脏线粒体的两个亚群中的任何一个的氧化代谢，即位于质膜下方的肌膜下线粒体（SSM）或位于肌原纤维之间的肌原纤维间线粒体（IFM）。从6个月大的成年和24个月及28个月大的老年Fischer 344大鼠心脏中分离出SSM和IFM。与衰老相关的改变仅限于IFM，而SSM未受影响。衰老降低了IFM中的氧化磷酸化速率，包括在由细胞色素氧化酶特异性电子供体刺激时。衰老心脏的IFM中细胞色素氧化酶的酶活性降低，而SSM中的活性与成年对照组相似。这些发现使得未来关于氧化功能与衰老相关下降的研究能够专注于IFM，而SSM则提供了一组内在的线粒体对照组，其氧化功能没有与衰老相关的改变。衰老过程中IFM的选择性改变增加了衰老诱导的线粒体功能障碍的后果将在衰老心肌细胞的特定亚细胞区域中增强的可能性。
