Mitochondrial disease in superoxide dismutase 2 mutant mice
Mitochondrial disease in superoxide dismutase 2 mutant mice
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DOI：
10.1073/pnas.96.3.846
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发表时间：
1999-02-02
影响因子：
11.1
通讯作者：
Wallace, DC
中科院分区：
文献类型：
--
作者：
Melov, S;Coskun, P;Wallace, DC
氧化应激与许多疾病有关。细胞内活性氧的主要来源是线粒体。我们已经描述了小鼠线粒体超氧化物歧化酶（CD1-Sod2(tm1Cje)）基因失活的各种生化和代谢影响。Sod2突变小鼠表现出呼吸链酶nadh脱氢酶（复合体I）和琥珀酸脱氢酶（复合体II）的组织特异性抑制，三羧酸循环酶乌头酸酶失活，尿有机酸尿并伴有3-羟基-3 -甲基戊二酰辅酶a分解酶的部分缺陷，以及氧化性DNA损伤的积累。这些结果表明，线粒体活性氧的增加可导致生化畸变，其特征与线粒体肌病、弗里德赖希共济失调和3-羟基-3-甲基戊二酰辅酶a裂解酶缺乏症相似。
Oxidative stress has been implicated in many diseases. The chief source of reactive oxygen species within the cell is the mitochondrion. We have characterized a variety of the biochemical and metabolic effects of inactivation of the mouse gene for the mitochondrial superoxide dismutase (CD1-Sod2(tm1Cje)). The Sod2 mutant mice exhibit a tissue-specific inhibition of the respiratory chain enzymes NADH-dehydrogenase (complex I) and succinate dehydrogenase (complex II), inactivation of the tricarboxylic acid cycle enzyme aconitase, development of a urine organic aciduria in conjunction with a partial defect in 3-hydroxy-3 -methylglutaryl-CoA lyase, and accumulation of oxidative DNA damage. These results indicate that the increase in mitochondrial reactive oxygen species can result in biochemical aberrations with features reminiscent of mitochondrial myopathy, Friedreich ataxia, and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.