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

Research output: Contribution to journalArticlepeer-review

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

ASJC Scopus subject areas

  • General

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