Cited by 581Mitochondrial Function and PathologyMetabolism and Genetic DisordersRedox biology and oxidative stress

Mitochondrial disease in superoxide dismutase 2 mutant mice

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Melov, Simon, Coskun, Pinar, Patel, Manisha, Tuinstra, Robbyn, Cottrell, Barbara, Jun, Albert S., Zastawny, Tomsz H., Dizdaroglu, Miral +5 more·1999·Proceedings of the National Academy of Sciences

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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Crossref · 10.1073/pnas.96.3.846

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  • Mice whose hematopoietic system was reconstituted with HSCs lacking Sod2 show oxidative stress-mediated hematopoietic abnormalities.

    “Mice whose hematopoietic system was reconstituted with HSCs lacking the gene encoding superoxide dismutase 2 (Sod2), a mitochondrial antioxidant enzyme regulated by FoxO3, showed oxidative stress–mediated hematopoietic abnormalities22.”

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Authors
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.
Affiliations
  • National Institute of Standards and Technology (US)
  • Center for Molecular Medicine, Emory University, Atlanta, GA 30322; National Jewish Medical and Research Center, Denver, CO 80206; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226; National Institute of Standards and Technology, Gaithersburg, MD 20899; Department of Pediatrics, University of Colorado School of Medicine, Denver, CO 80262; and Division of Medical Genetics, University of California at San Francisco, San Francisco, CA 94143-0748
Venue
Proceedings of the National Academy of Sciences
Published
1999-02-02
Volume
96
Issue
3
Pages
846-851
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2042138106
Cited by
581
References
75
Citations by year
2026: 1 · 2025: 7 · 2024: 12 · 2023: 14 · 2022: 10 · 2021: 11 · 2020: 16 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 11 · 2015: 17 · 2014: 23 · 2013: 20 · 2012: 16
FWCI
15.04
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl045572-08, HD-04024)
  • National Institute of Standards and Technology
  • National Institute on Aging (AG-13154, R01AG013154)
  • National Heart, Lung, and Blood Institute (HL45572)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R37DK021491, R01DK021491)
  • National Institute of Neurological Disorders and Stroke (NS-21328, R01NS021328)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD004024)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
mitochondrial superoxide dismutase, oxidative stress, reactive oxygen species, mitochondrial disease, NADH dehydrogenase complex I, aconitase, organic aciduria, HMG-CoA lyase deficiency, oxidative DNA damage, Friedreich's ataxia, mitochondrial myopathy, TCA cycle
MeSH terms
Aconitate Hydratase, Animals, Brain, Carboxylic Acids, Crosses, Genetic, DNA Damage, Female, Fumarate Hydratase, Oxo-Acid-Lyases, Male, Mice, Mutant Strains, Mitochondria, Mitochondria, Heart, Mitochondria, Muscle, Oxidative Phosphorylation, Superoxide Dismutase, Mitochondrial Myopathies, Reactive Oxygen Species, Mice

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