Mitochondrial disease in superoxide dismutase 2 mutant mice
Open accessAbstract
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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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.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [22]
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The physiological regulation of uncoupling proteins
Nicholls, D. G. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.02.005 · Cited by 183 · see citing works
Mitochondrial Oxidative Stress: Physiologic Consequences and Potential for a Role in Aging
MELOV, S. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06649.x · Cited by 161 · see citing works
Self-citationMitochondrial oxidative stress causes chromosomal instability of mouse embryonic fibroblasts
Samper, E., Nicholls, D. G., & Melov, S. (2003) · Aging Cell · doi:10.1046/j.1474-9728.2003.00062.x · Cited by 108 · see citing works
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Liang, R., & Ghaffari, S. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5300 · Cited by 106 · see citing works
Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells
Velarde, M. C., Demaria, M., Melov, S., & Campisi, J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1505675112 · Cited by 77 · see citing works
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Ganini, D., Santos, J. H., Bonini, M. G., & Mason, R. P. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2018.01.007 · Cited by 59 · see citing works
Long chain fatty acyl-CoA modulation of H2O2 release at mitochondrial complex I
Bortolami, S., Comelato, E., Zoccarato, F., Alexandre, A., & Cavallini, L. (2008) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-008-9126-1 · Cited by 13 · see citing works
- 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
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-02-02
- Volume
- 96
- Issue
- 3
- Pages
- 846-851
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC15313
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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