Mitochondrial disease in superoxide dismutase 2 mutant mice

Simon Melov; Pinar Coskun; Manisha Patel; Robbyn Tuinstra; Barbara Cottrell; Albert S. Jun; Tomsz H. Zastawny; Miral Dizdaroglu; Stephen I. Goodman; Ting Ting Huang; Henry Miziorko; Charles J. Epstein; Douglas C. Wallace

doi:10.1073/pnas.96.3.846

Mitochondrial disease in superoxide dismutase 2 mutant mice

Simon Melov, Pinar Coskun, Manisha Patel, Robbyn Tuinstra, Barbara Cottrell, Albert S. Jun, Tomsz H. Zastawny, Miral Dizdaroglu, Stephen I. Goodman, Ting Ting Huang, Henry Miziorko, Charles J. Epstein, Douglas C. Wallace

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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.

Original language	English (US)
Pages (from-to)	846-851
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	96
Issue number	3
DOIs	https://doi.org/10.1073/pnas.96.3.846
State	Published - Feb 2 1999
Externally published	Yes

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Melov, S., Coskun, P., Patel, M., Tuinstra, R., Cottrell, B., Jun, A. S., Zastawny, T. H., Dizdaroglu, M., Goodman, S. I., Huang, T. T., Miziorko, H., Epstein, C. J., & Wallace, D. C. (1999). Mitochondrial disease in superoxide dismutase 2 mutant mice. Proceedings of the National Academy of Sciences of the United States of America, 96(3), 846-851. https://doi.org/10.1073/pnas.96.3.846

Melov, S, Coskun, P, Patel, M, Tuinstra, R, Cottrell, B, Jun, AS, Zastawny, TH, Dizdaroglu, M, Goodman, SI, Huang, TT, Miziorko, H, Epstein, CJ & Wallace, DC 1999, 'Mitochondrial disease in superoxide dismutase 2 mutant mice', Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 3, pp. 846-851. https://doi.org/10.1073/pnas.96.3.846

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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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AU - Jun, Albert S.

AU - Zastawny, Tomsz H.

AU - Dizdaroglu, Miral

AU - Goodman, Stephen I.

AU - Huang, Ting Ting

AU - Miziorko, Henry

AU - Epstein, Charles J.

AU - Wallace, Douglas C.

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N2 - 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.

AB - 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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Mitochondrial disease in superoxide dismutase 2 mutant mice

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