Mitochondrial disease in superoxide dismutase 2 mutant mice

Oxidative stress has been implicated in many diseases. The chief source of reactive oxygen species within the cell is the mitochondrion. We have chara cterized a variety of the biochemical and metabolic effects of inactivation of the mouse gene for the mitochondrial superoxide dismutase (CD1-Sod2(tm1 Cje)). The Sod2 mutant mice exhibit a tissue-specific inhibition of the res piratory chain enzymes NADH-dehydrogenase (complex I) and succinate dehydro genase (complex II), inactivation of the tricarboxylic acid cycle enzyme ac onitase, development of a urine organic aciduria in conjunction with a part ial defect in 3-hydroxy-3 -methylglutaryl-CoA lyase, and accumulation of ox idative DNA damage. These results indicate that the increase in mitochondri al reactive oxygen species can result in biochemical aberrations with featu res reminiscent of mitochondrial myopathy, Friedreich ataxia, and 3-hydroxy -3-methylglutaryl-CoA lyase deficiency.