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Cited by 228Redox biology and oxidative stressSelenium in Biological SystemsMitochondrial Function and Pathology

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

Mitochondrial oxidative stress in mice lacking the glutathione peroxidase-1 gene

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Esposito, Luke A., Kokoszka, Jason E., Waymire, Katrina G., Cottrell, Barbara, MacGregor, Grant R., Wallace, Douglas C.·2000·Free Radical Biology and Medicine
DOI 10.1016/s0891-5849(00)00161-1PMC PMC3049813
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Abstract

Oxidative stress resulting from mitochondrially derived reactive oxygen species (ROS) has been hypothesized to damage mitochondrial oxidative phosphorylation (OXPHOS) and to be a factor in aging and degenerative disease. If this hypothesis is correct, then genetically inactivating potential mitochondrial antioxidant enzymes such as glutathione peroxidase-1 (Gpx1; EC 1.11.1.9) should increase mitochondrial ROS production and decrease OXPHOS function. To determine the expression pattern of Gpx1, isoform-specific antibodies were generated and mutant mice were prepared in which the Gpx1 protein was substituted for by beta-galactosidase, driven by the Gpx1 promoter. These experiments revealed that Gpx1 is highly expressed in both the mitochondria and the cytosol of the liver and kidney, but poorly expressed in heart and muscle. To determine the physiological importance of Gpx1, mice lacking Gpx1 were generated by targeted mutagenesis in mouse ES cells. Homozygous mutant Gpx1(tm1Mgr) mice have 20% less body weight than normal animals and increased levels of lipid peroxides in the liver. Moreover, the liver mitochondria were found to release markedly increased hydrogen peroxide, a Gpx1 substrate, and have decreased mitochondrial respiratory control ratio and power output index. Hence, genetic inactivation of Gpx1 resulted in growth retardation, presumably due in part to reduced mitochondrial energy production as a product of increased oxidative stress.

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  1. Esworthy, 1998, Selenium-dependent glutathione peroxidase-GI is a major glutathione peroxidase activity in the mucosal epithelium of rodent intestine, Biochim. Biophys. Acta, 1381, 213, 10.1016/S0304-4165(98)00032-4 · DOI

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Metadata

Authors
Esposito, L. A., Kokoszka, J. E., Waymire, K. G., Cottrell, B., MacGregor, G. R., & Wallace, D. C.
Affiliations
Emory University (US)
Corresponding author
Wallace, Douglas C.
ORCID
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2000-03
Volume
28
Issue
5
Pages
754-766
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/s0891-5849(00)00161-1
PMC
PMC3049813
OpenAlex
W2002860741
Cited by
228
References
47
Citations by year
2026: 5 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 9 · 2019: 5 · 2018: 11 · 2017: 7 · 2016: 5 · 2015: 3 · 2014: 8 · 2013: 10 · 2012: 6
FWCI
5.43
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (AG-13154, R01AG013154)
  • National Institute of General Medical Sciences (T32GM008490)
  • National Institute of Neurological Disorders and Stroke (NS-21328, R01NS021328)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-36437, R01HD036437)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
glutathione peroxidase 1, mitochondrial oxidative stress, reactive oxygen species, oxidative phosphorylation, hydrogen peroxide, lipid peroxidation, growth retardation, liver mitochondria, respiratory control ratio, mitochondrial energy production, tissue-specific gene expression
MeSH terms
Glutathione Peroxidase GPX1, Animals, Base Sequence, Female, Free Radicals, Glutathione Peroxidase, Hydrogen Peroxide, Male, Mice, Inbred C57BL, Mitochondria, Mitochondria, Heart, Mitochondria, Liver, Oxygen Consumption, Pregnancy, DNA Primers, Mice, Knockout, Oxidative Stress, Mice, In Vitro Techniques

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