Petrosillo G, Matera M, Casanova G, Ruggiero F M, Paradies G
Department of Biochemistry and Molecular Biology, C.N.R. Institute of Biomembranes and Bioenergetics, University of Bari, Via E. Orabona 4, 70126 Bari, Italy.
Neurochem Int. 2008 Nov;53(5):126-31. doi: 10.1016/j.neuint.2008.07.001. Epub 2008 Jul 9.
Reactive oxygen species (ROS) are considered a key factor in brain aging process. Mitochondrial respiration is an important site of ROS production and hence a potential contributor to brain functional changes with aging. In this study we examined the effect of aging on complex I activity, oxygen consumption, ROS production and phospholipid composition in rat brain mitochondria. The activity of complex I was reduced by 30% in brain mitochondria from 24 months aged rats relative to young animals. These changes in complex I activity were associated with parallel changes in state 3 respiration. H(2)O(2) generation was significantly increased in mitochondria isolated from aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, decreased by 31% as function of aging, while there was a significant increase in the level of peroxidized cardiolipin. The age-related decrease in complex I activity in brain mitochondria could be reversed by exogenously added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids. It is proposed that aging causes brain mitochondrial complex I dysfunction which can be attributed to ROS-induced cardiolipin oxidation. These findings may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with brain aging.
活性氧（ROS）被认为是大脑衰老过程中的一个关键因素。线粒体呼吸是ROS产生的重要场所，因此可能是导致大脑功能随衰老而变化的一个因素。在本研究中，我们检测了衰老对大鼠脑线粒体中复合物I活性、氧气消耗、ROS产生和磷脂组成的影响。与年轻动物相比，24月龄大鼠脑线粒体中复合物I的活性降低了30%。复合物I活性的这些变化与状态3呼吸的平行变化相关。从老年大鼠分离的线粒体中H(2)O(2)的生成显著增加。作为衰老的一个作用，复合物I最佳活性所需的磷脂心磷脂的线粒体含量下降了31%，而过氧化心磷脂的水平则显著增加。外源性添加心磷脂可逆转脑线粒体中与年龄相关的复合物I活性下降。心磷脂的这种作用不能被其他磷脂替代。有人提出，衰老会导致脑线粒体复合物I功能障碍，这可能归因于ROS诱导的心磷脂氧化。这些发现可能有助于阐明与脑衰老相关的线粒体功能障碍的潜在机制。
