ArticleMolecular genetics and metabolism2011
Increased superoxide accumulation in pyruvate dehydrogenase complex deficient fibroblasts.
Article in Molecular genetics and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Endothelial mitochondrial homeostasis in the development and progression of atherosclerosis.Frontiers in cardiovascular medicine · 2026Review
- Impacts of mitochondrial dysfunction on axonal microtubule bundles as a potential mechanism of neurodegeneration.Frontiers in neuroscience · 2025Review
- Review
- Cardiovascular Disease and miRNAs: Possible Oxidative Stress-Regulating Roles of miRNAs.Antioxidants (Basel, Switzerland) · 2024Review
- Pyruvate Dehydrogenase Complex in Neonatal Hypoxic-Ischemic Brain Injury.ACS pharmacology & translational science · 2024Review
- Sex-specific alteration in human muscle transcriptome with age.GeroScience · 2023Article
- The Key Role of Mitochondrial Function in Health and Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon Japanese encephalitis virus infection.IBRO neuroscience reports · 2022Article
- Thiamine and selected thiamine antivitamins - biological activity and methods of synthesis.Bioscience reports · 2018Review
- Drosophila as a Model to Study the Link between Metabolism and Cancer.Journal of developmental biology · 2017Review
- Mitochondrial dysfunction and its impact on diabetic heart.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
- Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions.Cancer discovery · 2016Review
- Article
- Severe encephalopathy associated to pyruvate dehydrogenase mutations and unbalanced coenzyme Q10 content.European journal of human genetics : EJHG · 2016Article
- Altered Protein Expression in the Ileum of Mice Associated with the Development of Chronic Infections with Echinostoma caproni (Trematoda).PLoS neglected tropical diseases · 2015Article
- Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets.Diabetes · 2014Article
- Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors.Investigational new drugs · 2014Article
- Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The pyruvate dehydrogenase complex (PDC) oxidizes pyruvate to acetyl CoA and is critically important in maintaining normal cellular energy homeostasis. Loss-of-function mutations in PDC give rise to congenital lactic acidosis and to progressive cellular energy failure. However, the subsequent biochemical consequences of PDC deficiency that may contribute to the clinical manifestations of the disorder are poorly understood. We postulated that altered flux through PDC would disrupt mitochondrial electron transport, resulting in oxidative stress. Compared to cells from 4 healthy subjects, primary cultures of skin fibroblasts from 9 patients with variable mutations in the gene encoding the alpha subunit (E1α) of pyruvate dehydrogenase (PDA1) demonstrated reduced growth and viability. Superoxide (O(2)(.-)) from the Qo site of complex III of the electron transport chain accumulated in these cells and was associated with decreased activity of manganese superoxide dismutase. The expression of uncoupling protein 2 was also decreased in patient cells, but there were no significant changes in the expression of cellular markers of protein or DNA oxidative damage. The expression of hypoxia transcription factor 1 alpha (HIF1α) also increased in PDC deficient fibroblasts. We conclude that PDC deficiency is associated with an increase in O(2)(.-) accumulation coupled to a decrease in mechanisms responsible for its removal. Increased HIF1α expression may contribute to the increase in glycolytic flux and lactate production in PDC deficiency and, by trans-activating pyruvate dehydrogenase kinase, may further suppress residual PDC activity through phosphorylation of the E1α subunit.
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What OpenQuestion holds
Registered trials
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