Mitochondrial disease in superoxide dismutase 2 mutant mice

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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)846-851
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number3
DOIs
StatePublished - Feb 2 1999
Externally publishedYes

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Electron Transport Complex I
Mitochondrial Diseases
Reactive Oxygen Species
Mitochondrial Myopathies
Aconitate Hydratase
Friedreich Ataxia
Lyases
Mitochondrial Genes
Citric Acid Cycle
Succinate Dehydrogenase
Enzymes
Electron Transport
DNA Damage
Superoxide Dismutase
Mitochondria
Oxidative Stress
Urine
superoxide dismutase 2
3-hydroxy-3-methylglutaryl-coenzyme A
Metabolic Inactivation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Mitochondrial disease in superoxide dismutase 2 mutant mice. / Melov, Simon; Coskun, Pinar; Patel, Manisha; Tuinstra, Robbyn; Cottrell, Barbara; Jun, Albert; Zastawny, Tomsz H.; Dizdaroglu, Miral; Goodman, Stephen I.; Huang, Ting Ting; Miziorko, Henry; Epstein, Charles J.; Wallace, Douglas C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 3, 02.02.1999, p. 846-851.

Research output: Contribution to journalArticle

Melov, S, Coskun, P, Patel, M, Tuinstra, R, Cottrell, B, Jun, A, 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
Melov, Simon ; Coskun, Pinar ; Patel, Manisha ; Tuinstra, Robbyn ; Cottrell, Barbara ; Jun, Albert ; Zastawny, Tomsz H. ; Dizdaroglu, Miral ; Goodman, Stephen I. ; Huang, Ting Ting ; Miziorko, Henry ; Epstein, Charles J. ; Wallace, Douglas C. / Mitochondrial disease in superoxide dismutase 2 mutant mice. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 3. pp. 846-851.
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