ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 299 papers, 1 of them a synthesis that pooled it.
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Who cites it
299 citing papers in PubMed, 1 synthesis or guideline pooled it, 681 citations in OpenAlex.
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- Superoxide signals for the mitophagy of dysfunctional mitochondria to maintain quality control.Redox biology · 2026Review
- Animal models of pyruvate dehydrogenase complex deficiency: insight into mechanisms of cerebral abnormalities and tissue-specific role in metabolism.Frontiers in medicine · 2026Review
- Redox System Dysfunction as a Key Mechanism in Autism Spectrum Disorder Pathogenesis.International journal of molecular sciences · 2025Review
- Mitochondrial CaJournal of cellular physiology · 2025Review
- Thiamine (Vitamin B1)-An Essential Health Regulator.Nutrients · 2025Review
- Aerobic exercise-induced changes in fluid biomarkers in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Mitochondrial dysfunction in the regulation of aging and aging-related diseases.Cell communication and signaling : CCS · 2025Review
- Targeted Redox Regulation α-Ketoglutarate Dehydrogenase Complex for the Treatment of Human Diseases.Cells · 2025Review
- Ferroptosis: iron release mechanisms in the bioenergetic process.Cancer metastasis reviews · 2025Review
- Bioenergetic adaptations of small intestinal epithelial cells reduce cell differentiation enhancing intestinal permeability in obese mice.Molecular metabolism · 2025Article
- The Role of Cuproptosis in Hyperoxia-Induced Lung Injury and Its Potential for Treatment.Journal of inflammation research · 2025Article
- Enhanced ROS Production and Mitochondrial Metabolic Shifts in CD4International journal of molecular sciences · 2024Article
- Molecular architecture of the mammalian 2-oxoglutarate dehydrogenase complex.Nature communications · 2024Article
- Higher abundance of DLD protein in buffalo bull spermatozoa causes elevated ROS production leading to early sperm capacitation and reduction in fertilizing ability.Journal of animal science and biotechnology · 2024Article
239 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Mitochondria-produced reactive oxygen species (ROS) are thought to contribute to cell death caused by a multitude of pathological conditions. The molecular sites of mitochondrial ROS production are not well established but are generally thought to be located in complex I and complex III of the electron transport chain. We measured H(2)O(2) production, respiration, and NADPH reduction level in rat brain mitochondria oxidizing a variety of respiratory substrates. Under conditions of maximum respiration induced with either ADP or carbonyl cyanide p-trifluoromethoxyphenylhydrazone,alpha-ketoglutarate supported the highest rate of H(2)O(2) production. In the absence of ADP or in the presence of rotenone, H(2)O(2) production rates correlated with the reduction level of mitochondrial NADPH with various substrates, with the exception of alpha-ketoglutarate. Isolated mitochondrial alpha-ketoglutarate dehydrogenase (KGDHC) and pyruvate dehydrogenase (PDHC) complexes produced superoxide and H(2)O(2). NAD(+) inhibited ROS production by the isolated enzymes and by permeabilized mitochondria. We also measured H(2)O(2) production by brain mitochondria isolated from heterozygous knock-out mice deficient in dihydrolipoyl dehydrogenase (Dld). Although this enzyme is a part of both KGDHC and PDHC, there was greater impairment of KGDHC activity in Dld-deficient mitochondria. These mitochondria also produced significantly less H(2)O(2) than mitochondria isolated from their littermate wild-type mice. The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria.
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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.