ArticleThe Journal of biological chemistry2012
Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Regulation of PDH via cysteine oxidation on DLAT.Nature communications · 2026Article
- Regulating Glucose Metabolism Enzymes for Osteoporosis Therapy: Current and Future Approaches.International journal of molecular sciences · 2026Review
- Protein oxidation in crowded environments.The Biochemical journal · 2026Review
- Mitochondrial Iron Handling and Lipid Peroxidation as Drivers of Ferroptosis.International journal of molecular sciences · 2026Review
- The flexible chain: regulation of structure and activity of ETC complexes defines rate of ATP synthesis and sites of superoxide generation.Biophysical reviews · 2025Review
- Metabolic Responses to Redox Stress in Vascular Cells.Antioxidants & redox signaling · 2024Review
- Cysteine induces mitochondrial reductive stress in glioblastoma through hydrogen peroxide production.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
- Gut microbes involvement in gastrointestinal cancers through redox regulation.Gut pathogens · 2023Review
- Redox regulation of the immune response.Cellular & molecular immunology · 2022Review
- Reactive Oxygen Species and Metabolism in Leukemia: A Dangerous Liaison.Frontiers in immunology · 2022Review
- The Dawn of Mitophagy: What Do We Know by Now?Current neuropharmacology · 2021Review
- [A Review of the Redox Regulation of Tumor Metabolism].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Review
- Electrophile Modulation of Inflammation: A Two-Hit Approach.Metabolites · 2020Review
- The interplay between oxidative stress and bioenergetic failure in neuropsychiatric illnesses: can we explain it and can we treat it?Molecular biology reports · 2020Review
- Immunological Techniques to Assess Protein Thiol Redox State: Opportunities, Challenges and Solutions.Antioxidants (Basel, Switzerland) · 2020Review
- Article
- The Impact of Oxidative Stress on Adipose Tissue Energy Balance.Frontiers in physiology · 2019Review
- Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer.Antioxidants & redox signaling · 2018Review
- Pyruvate dehydrogenase complex stimulation promotes immunometabolic homeostasis and sepsis survival.JCI insight · 2018Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Reactive oxygen species are byproducts of mitochondrial respiration and thus potential regulators of mitochondrial function. Pyruvate dehydrogenase kinase 2 (PDHK2) inhibits the pyruvate dehydrogenase complex, thereby regulating entry of carbohydrates into the tricarboxylic acid (TCA) cycle. Here we show that PDHK2 activity is inhibited by low levels of hydrogen peroxide (H(2)O(2)) generated by the respiratory chain. This occurs via reversible oxidation of cysteine residues 45 and 392 on PDHK2 and results in increased pyruvate dehydrogenase complex activity. H(2)O(2) derives from superoxide (O(2)(.)), and we show that conditions that inhibit PDHK2 also inactivate the TCA cycle enzyme, aconitase. These findings suggest that under conditions of high mitochondrial O(2)(.) production, such as may occur under nutrient excess and low ATP demand, the increase in O(2)() and H(2)O(2) may provide feedback signals to modulate mitochondrial 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.