Mitochondrial free radical production and aging in mammals and birds
Mitochondrial free radical production and aging in mammals and birds
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DOI：
10.1111/j.1749-6632.1998.tb09905.x
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Barja, G
中科院分区：
文献类型：
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作者：
Barja, G
在哺乳动物中，线粒体产生氧自由基(ROS)的速率与最大寿命潜势(MLSP)呈负相关，遵循生存速率理论。为了知道这种关系是否不仅仅是间接的，必须研究具有MLSP的恒温脊椎动物，这些脊椎动物的MLSP不同于大多数哺乳动物(如鸟类和灵长类)的身体大小和代谢率预测的MLSP。鸟类是独一无二的，因为它们结合了高基础耗氧率和高MLSP。心脏、脑和肺线粒体ROS的产生和自由基漏出(现在指向ROS产生的总电子的百分比)在三种不同目的鸟类中低于身体大小和代谢率相似的哺乳动物。这表明，表现出低ROS生成率的能力是鸟类的一个普遍特征。使用针对呼吸链不同片段的底物和抑制剂，状态4的主要ROS产生部位(负责这些鸟类与哺乳动物的差异)已定位于心脏线粒体的复合体I和III，仅位于非突触脑线粒体的复合体I，在状态3，复合体I是这两个组织中唯一的生成物。结果还表明，铁-硫中心是络合物I的ROS生成器。允许鸽子线粒体显示低ROS生成率的一般机制是维持ROS生成器位置的低程度还原的能力。在心脏线粒体中，这与相对较大的心脏大小在生理上补偿的低耗氧速率、接近DNA的低自由基产生速率以及高DNA修复速率相结合，可以导致DNA损伤的缓慢积累速度，从而导致长寿动物的缓慢衰老。
The mitochondrial rate of oxygen radical (ROS) production is negatively correlated with maximum life span potential (MLSP) in mammals following the rate of living theory. In order to know if this relationship is more than circumstantial, homeothermic vertebrates with MLSP different from that predicted by the body size and metabolic rate of the majority of mammals (like birds and primates) must he studied. Birds are unique because they combine a high rate of basal oxygen consumption with a high MLSP. Heart, brain, and lung mitochondrial ROS production and free radical leak (percent of total electron now directed to ROS production) are lower in three species of birds of different orders than in mammals of similar body size and metabolic rate. This suggests that the capacity to show a low rate of ROS production is a general characteristic of birds. Using substrates and inhibitors specific for different segments of the respiratory chain, the main ROS generator site (responsible for those bird-mammalian differences) In state 4 has been localized at complexes I and III in heart mitochondria and only at complex I in nonsynaptic brain mitochondria, In state 3, complex I is the only generator in both tissues. The results also suggest that the iron-sulphur centers are the ROS generators of complex I. A general mechanism that allows pigeon mitochondria to show a low rate of ROS production ran be the capacity to maintain a low degree of reduction of the ROS generator site. In heart mitochondria, this is supplemented with a low rate of oxygen consumption physiologically compensated with a comparatively higher heart size, A low rate of free radical production near DNA, together with a high rate of DNA repair, can be responsible for the slow rate of accumulation of DNA damage and thus the slow aging rate of longevous animals.