Enhanced catabolism of mitochondrial superoxide/hydrogen peroxide and aging in transgenic Drosophila
Enhanced catabolism of mitochondrial superoxide/hydrogen peroxide and aging in transgenic Drosophila
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DOI：
10.1042/bj20041872
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发表时间：
2005-10-15
影响因子：
4.1
通讯作者：
Sohal, RS
中科院分区：
文献类型：
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作者：
Bayne, ACV;Mockett, RJ;Sohal, RS
线粒体呼吸过程中产生的超氧阴离子自由基（O-2）和过氧化氢（H2O2）被广泛认为与衰老过程有因果关系。通过同时过表达锰超氧化物歧化酶（MnSOD）和过氧化氢酶（过氧化氢酶），特异靶向转基因黑腹果蝇线粒体基质，验证了线粒体O-2（中心点-）/H2O2分解代谢特异性增强可延缓年龄相关生理变化并延长寿命的假设。这些抗氧化酶活性的增加导致线粒体H2O2释放减少，游离蛋氨酸含量增加。MnSOD/线粒体过氧化氢酶转基因果蝇在饮食中添加H2O2或暴露于100%环境氧诱导的实验氧化应激中表现出增强的抗性。然而，果蝇的寿命减少了43%，这种影响与(i)身体健康的整体下降（通过步行速度来衡量）和（ii）线粒体状态3 （adp刺激）呼吸的年龄相关减少相吻合。这些发现支持了线粒体O-2（中心点-）/H2O2在生理水平上的产生对于正常生物过程至关重要，从而实现正常寿命。
The generation of superoxide anion radicals (O-2(center dot-)) and hydrogen peroxide (H2O2) during mitochondrial respiration has been widely postulated to be causally linked to the aging process. The hypothesis that a specific enhancement of mitochondrial O-2(center dot-)/H2O2 catabolism would delay age-associated physiological changes and extend the lifespan was tested by simultaneous overexpression of MnSOD (manganese superoxide dismutase) and catalase, ectopically targeted to the mitochondrial matrix of transgenic Drosophila melanogaster. The increased activities of these antioxidative enzymes resulted in a decrease of mitochondrial H2O2 release and enhancement of free methionine content. The MnSOD/mitochondrial catalase transgenic flies displayed an enhanced resistance to experimental oxidative stress, induced by dietary H2O2 administration or by exposure to 100% ambient oxygen. However, the lifespan of the flies was decreased, by up to 43 %, and this effect coincided with (i) an overall decrease in physical fitness, as measured by the speed of walking, and (ii) an age-related decrease in mitochondrial state 3 (ADP-stimulated) respiration. These findings support the notion that mitochondrial O-2(center dot-)/H2O2 production at physiological levels is essential for normal biological processes leading to the attainment of a normal lifespan.