Mitochondrial disease in superoxide dismutase 2 mutant mice

TLDR

Oxidative stress, largely generated by mitochondrial reactive oxygen species, is implicated in many diseases. Inactivation of the mitochondrial superoxide dismutase gene in mice causes tissue‑specific inhibition of respiratory chain complexes I and II, loss of aconitase activity, organic aciduria with a partial HMG‑CoA lyase defect, and oxidative DNA damage, mimicking features of mitochondrial myopathy, Friedreich ataxia, and HMG‑CoA lyase deficiency.

Abstract

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.