Mitochondrial disease in superoxide dismutase 2 mutant mice

Simon Melov(National Institute of Standards and Technology), Pınar Coşkun(National Institute of Standards and Technology), Manisha Patel(National Institute of Standards and Technology), Robbyn L. Tuinstra(National Institute of Standards and Technology), Barbara A. Cottrell(National Institute of Standards and Technology), Albert S. Jun(National Institute of Standards and Technology), Tomsz H. Zastawny(National Institute of Standards and Technology), Miral Dizdaroğlu(National Institute of Standards and Technology), Stephen I. Goodman(National Institute of Standards and Technology), Ting‐Ting Huang(National Institute of Standards and Technology), Henry M. Miziorko(National Institute of Standards and Technology), Charles J. Epstein(National Institute of Standards and Technology), Douglas C. Wallace(National Institute of Standards and Technology)
Proceedings of the National Academy of Sciences
February 2, 1999
10.1073/pnas.96.3.846
Cited by 581Open Access

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.

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