{"doi":"10.1089/ars.2005.7.1140","title":"Production of Reactive Oxygen Species in Brain Mitochondria: Contribution by Electron Transport Chain and Non–Electron Transport Chain Sources","abstract":null,"journal":"Antioxidants & Redox Signaling","year":2005,"id":688824,"datarank":0.9130162090368461,"base_score":6.0867747269123065,"endowment":6.0867747269123065,"self_citation_contribution":0.9130162090368461,"citation_network_contribution":0.0,"self_endowment_contribution":0.9130162090368461,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":439,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1799549,"name":"Vera Adam-Vizi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Production of Reactive Oxygen Species in Brain Mitochondria: Contribution by Electron Transport Chain and Non–Electron Transport Chain Sources","abstract":"Overwhelming evidence has accumulated indicating that oxidative stress is a crucial factor in the pathogenesis of neurodegenerative diseases. The major site of production of superoxide, the primary reactive oxygen species (ROS), is considered to be the respiratory chain in the mitochondria, but the exact mechanism and the precise location of the physiologically relevant ROS generation within the respiratory chain have not been disclosed as yet. Studies performed with isolated mitochondria have located ROS generation on complex I and complex III, respectively, depending on the substrates or inhibitors used to fuel or inhibit respiration. A more \"physiological\" approach is to address ROS generation of in situ mitochondria, which are present in their normal cytosolic environment. Hydrogen peroxide formation in mitochondria in situ in isolated nerve terminals is enhanced when complex I, complex III, or complex IV is inhibited. However, to induce a significant increase in ROS production, complex III and complex IV have to be inhibited by >70%, which raises doubts as to the physiological importance of ROS generation by these complexes. In contrast, complex I inhibition to a small degree is sufficient to enhance ROS generation, indicating that inhibition of complex I by approximately 25-30% observed in postmortem samples of substantia nigra from patients suffering from Parkinson's disease could be important in inducing oxidative stress. Recently, it has been described that a key Krebs cycle enzyme, alpha-ketoglutarate dehydrogenase (alpha-KGDH), is also able to produce ROS. ROS formation by alpha-KGDH is regulated by the NADH/NAD+ ratio, suggesting that this enzyme could substantially contribute to generation of oxidative stress due to inhibition of complex I. As alpha-KGDH is not only a generator but also a target of ROS, it is proposed that alpha-KGDH is a key factor in a vicious cycle by which oxidative stress is induced and promoted in nerve terminals.","is_dataset_classified":null,"base_score":6.0867747269123065,"endowment":6.0867747269123065,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16115017","pmcid":null,"openalex_id":"https://openalex.org/W1986790448","authors":[],"funders":[],"total_grants":0,"fwci":6.7693,"citation_percentile":0.97816805,"influential_citations":0,"citation_trend":[{"year":2012,"count":34},{"year":2013,"count":26},{"year":2014,"count":28},{"year":2015,"count":27},{"year":2016,"count":25},{"year":2017,"count":23},{"year":2018,"count":25},{"year":2019,"count":27},{"year":2020,"count":24},{"year":2021,"count":13},{"year":2022,"count":19},{"year":2023,"count":10},{"year":2024,"count":14},{"year":2025,"count":5},{"year":2026,"count":7}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://www.liebertpub.com/doi/pdf/10.1089/ars.2005.7.1140","host_type":"publisher"},{"url":"https://doi.org/10.1089/ars.2005.7.1140","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16115017","host_type":"repository"}],"fields_of_study":["Mitochondrial Function and Pathology","Parkinson's Disease Mechanisms and Treatments","Alzheimer's disease research and treatments","Animals","Brain","Electron Transport","Electron Transport Chain Complex Proteins","Gene Expression Regulation, Enzymologic","Humans","Hydrogen Peroxide","Ketoglutarate Dehydrogenase Complex","Membrane Potentials","Mitochondria","Models, Biological","N-Methylaspartate","Oxidative Stress","Rats","Reactive Oxygen Species","Superoxide Dismutase","Superoxides"],"mesh_terms":["Animals","Brain","Electron Transport","Humans","Hydrogen Peroxide","Ketoglutarate Dehydrogenase Complex","Membrane Potentials","Mitochondria","Models, Biological","Superoxides","Superoxide Dismutase","Gene Expression Regulation, Enzymologic","N-Methylaspartate","Reactive Oxygen Species","Oxidative Stress","Electron Transport Chain Complex Proteins","Rats"],"keywords":["Mitochondrion","Reactive oxygen species","Respiratory chain","Oxidative stress","Mitochondrial ROS","Mitochondrial respiratory chain","Electron Transport Complex I","Superoxide","Cell biology","Biochemistry","Electron transport chain","NAD+ kinase","Oxidative phosphorylation","Biology","Coenzyme Q – cytochrome c reductase","Dehydrogenase","Chemistry","Enzyme","Cytochrome c"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.20222605.v1","title":"Additional file 1 of Protective role of VEGF/VEGFR2 signaling against high fatality associated with hepatic encephalopathy via sustaining mitochondrial bioenergetics functions","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20222605","title":"Additional file 1 of Protective role of VEGF/VEGFR2 signaling against high fatality associated with hepatic encephalopathy via sustaining mitochondrial bioenergetics functions","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-19T19:31:09.404305Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}