ArticleThe Journal of biological chemistry2013
Glutaredoxin-2 is required to control proton leak through uncoupling protein-3.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 65 citations in OpenAlex.
- S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
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- The Uncoupling Proteins: A Systematic Review on the Mechanism Used in the Prevention of Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Review
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- Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells.Frontiers in oncology · 2021Article
- An investigation into the impact of deleting one copy of theRedox report : communications in free radical research · 2020Article
- Role of Glutathione in Cancer: From Mechanisms to Therapies.Biomolecules · 2020Review
- Changes in Northern Elephant Seal Skeletal Muscle Following Thirty Days of Fasting and Reduced Activity.Frontiers in physiology · 2020Article
- Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion forAntioxidants (Basel, Switzerland) · 2019Article
- Age-related loss of mitochondrial glutathione exacerbates menadione-induced inhibition of Complex I.Redox biology · 2019Article
- Characterization of the impact of glutaredoxin-2 (GRX2) deficiency on superoxide/hydrogen peroxide release from cardiac and liver mitochondria.Redox biology · 2018Article
- Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies.Redox biology · 2018Article
- Article
- A novel amino acid and metabolomics signature in mice overexpressing muscle uncoupling protein 3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Induction of mitochondrial reactive oxygen species production by GSH mediated S-glutathionylation of 2-oxoglutarate dehydrogenase.Redox biology · 2016Article
- Protein S-glutathionlyation links energy metabolism to redox signaling in mitochondria.Redox biology · 2016Review
- Detailed Biochemical and Bioenergetic Characterization of FBXL4-Related Encephalomyopathic Mitochondrial DNA Depletion.JIMD reports · 2016Article
- Paradoxical Roles of Antioxidant Enzymes: Basic Mechanisms and Health Implications.Physiological reviews · 2016Review
- Modulation of the matrix redox signaling by mitochondrial Ca(2.).World journal of biological chemistry · 2015Review
- Glutaredoxin 2a overexpression in macrophages promotes mitochondrial dysfunction but has little or no effect on atherogenesis in LDL-receptor null mice.Atherosclerosis · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Glutathionylation has emerged as a key modification required for controlling protein function in response to changes in cell redox status. Recently, we showed that the glutathionylation state of uncoupling protein-3 (UCP3) modulates the leak of protons back into the mitochondrial matrix, thus controlling reactive oxygen species production. However, whether or not UCP3 glutathionylation is mediated enzymatically has remained unknown because previous work relied on the use of pharmacological agents, such as diamide, to alter the UCP3 glutathionylation state. Here, we demonstrate that glutaredoxin-2 (Grx2), a matrix oxidoreductase, is required to glutathionylate and inhibit UCP3. Analysis of bioenergetics in skeletal muscle mitochondria revealed that knock-out of Grx2 (Grx2(-/-)) increased proton leak in a UCP3-dependent manner. These effects were reversed using diamide, a glutathionylation catalyst. Importantly, the increased leak did not compromise coupled respiration. Knockdown of Grx2 augmented proton leak-dependent respiration in primary myotubes from wild type mice, an effect that was absent in UCP3(-/-) cells. These results confirm that Grx2 deactivates UCP3 by glutathionylation. To our knowledge, this is the first enzyme identified to regulate UCP3 by glutathionylation and is the first study on the role of Grx2 in the regulation of energy metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.