Mitochondrial disease in superoxide dismutase 2 mutant mice

Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):846-51. doi: 10.1073/pnas.96.3.846.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aconitate Hydratase / deficiency
  • Aconitate Hydratase / metabolism
  • Animals
  • Brain / metabolism
  • Carboxylic Acids / metabolism
  • Carboxylic Acids / urine
  • Crosses, Genetic
  • DNA Damage
  • Female
  • Fumarate Hydratase / metabolism
  • Male
  • Mice
  • Mice, Mutant Strains
  • Mitochondria / metabolism
  • Mitochondria, Heart / metabolism*
  • Mitochondria, Muscle / metabolism*
  • Mitochondrial Myopathies / enzymology
  • Mitochondrial Myopathies / genetics*
  • Oxidative Phosphorylation*
  • Oxo-Acid-Lyases / deficiency
  • Oxo-Acid-Lyases / metabolism
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / deficiency*
  • Superoxide Dismutase / genetics*


  • Carboxylic Acids
  • Reactive Oxygen Species
  • Superoxide Dismutase
  • Oxo-Acid-Lyases
  • 3-hydroxy-3-methylglutaryl-coenzyme A lyase
  • Fumarate Hydratase
  • Aconitate Hydratase