ArticleFree radical biology & medicine2012
Protein thiyl radical mediates S-glutathionylation of complex I.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
- Targeting macro- and micro-nutrient regulation of HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Glutathione and Glutaredoxin-Key Players in Cellular Redox Homeostasis and Signaling.Antioxidants (Basel, Switzerland) · 2023Review
- S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Mitochondrial redox regulation and myocardial ischemia-reperfusion injury.American journal of physiology. Cell physiology · 2022Review
- Chaperone-Mediated Autophagy of eNOS in Myocardial Ischemia-Reperfusion Injury.Circulation research · 2021Article
- Redox Regulation by Protein S-Glutathionylation: From Molecular Mechanisms to Implications in Health and Disease.International journal of molecular sciences · 2020Review
- Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing.Antioxidants (Basel, Switzerland) · 2020Review
- Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage.International journal of molecular sciences · 2020Article
- Immunological Techniques to Assess Protein Thiol Redox State: Opportunities, Challenges and Solutions.Antioxidants (Basel, Switzerland) · 2020Review
- Review
- Dysregulation of the glutaredoxin/American journal of physiology. Cell physiology · 2020Article
- Mitochondrial complex I in the post-ischemic heart: reperfusion-mediated oxidative injury and protein cysteine sulfonation.Journal of molecular and cellular cardiology · 2018Article
- Differential protein acetylation assists import of excess SOD2 into mitochondria and mediates SOD2 aggregation associated with cardiac hypertrophy in the murine SOD2-tg heart.Free radical biology & medicine · 2017Article
- Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System: A Scientific Statement From the American Heart Association.Circulation research · 2016Review
- 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
- Impaired coronary metabolic dilation in the metabolic syndrome is linked to mitochondrial dysfunction and mitochondrial DNA damage.Basic research in cardiology · 2016Article
- Activation of mitochondrial calpain and increased cardiac injury: beyond AIF release.American journal of physiology. Heart and circulatory physiology · 2016Article
- The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies.Oxidative medicine and cellular longevity · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Complex I is a critical site of O(2)(•-) production and the major host of reactive protein thiols in mitochondria. In response to oxidative stress, complex I protein thiols at the 51- and 75-kDa subunits are reversibly S-glutathionylated. The mechanism of complex I S-glutathionylation is mainly obtained from insight into GSSG-mediated thiol-disulfide exchange, which would require a dramatic decline in the GSH/GSSG ratio. Intrinsic complex I S-glutathionylation can be detected in the rat heart at a relatively high GSH/GSSG ratio (J. Chen et al., J. Biol. Chem. 285:3168-3180, 2010). Thus, we hypothesized that reactive thiyl radical is more likely to mediate protein S-glutathionylation of complex I. Here we employed immuno-spin trapping and tandem mass spectrometry (LC/MS/MS) to test the hypothesis in the 75-kDa subunit from S-glutathionylated complex I. Under the conditions of O(2)(•-) production in the presence of GSH, we detected complex I S-glutathionylation at Cys-226, Cys-367, and Cys-727 of the 75-kDa subunit. Addition of a radical trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), significantly decreased complex I S-glutathionylation and subsequently increased the protein radical adduct of complex I-DMPO as detected by immunoblotting using an anti-DMPO antibody. LC/MS/MS analysis indicated that Cys-226, Cys-554, and Cys-727 were involved in DMPO binding, confirming that formation of the complex I thiyl radical mediates S-glutathionylation. LC/MS/MS analysis also showed that Cys-554 and Cys-727 were S-sulfonated under conditions of O(2)(•-) generation in the absence of DMPO. In myocytes (HL-1 cell line) treated with menadione to trigger mitochondrial O(2)(•-) generation, complex I protein radical and S-glutathionylation were increased. Thus mediation of complex I S-glutathionylation by the protein thiyl radical provides a unique pathway for the redox regulation of mitochondrial function.
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Registered trials
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