{"id":"9c493806-7356-57ce-832c-42528b84c0f6","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-complex-ii-inactivation","predicate":"decreases-assayed-activity","statement":"The same pharmacological ascorbate exposure reduced NSCLC respiratory-complex II activity, extending the observed impairment to a second Fe-S-containing respiratory complex; complex IV activity was retained.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"27237100-2d34-5b3c-afc1-3e9a3fe9ffcd","mechanism_event_label":"The exposure also impaired respiratory complex II, which participates in respiration and the citric acid cycle.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"4dc2faa3-f38c-5813-b7f2-fe19a0ab7bfa","slug":"respiratory-complex-ii","display_name":"Respiratory complex II","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"27237100-2d34-5b3c-afc1-3e9a3fe9ffcd","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-complex-ii-inactivation-event","event_type":"biochemical_relationship","label":"The exposure also impaired respiratory complex II, which participates in respiration and the citric acid cycle.","description":"The same pharmacological ascorbate exposure reduced NSCLC respiratory-complex II activity, extending the observed impairment to a second Fe-S-containing respiratory complex; complex IV activity was retained.","status":"provisional","compartment":{"slug":"mitochondria","display_name":"Mitochondria"},"participants":[{"entity":{"id":"da1a7137-08f2-5a36-8bb6-377fbd32e327","slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"},"role":"nutrient context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8058ae47-b091-5004-ba65-1e50ad91f70b","slug":"iron-sulfur-4fe4s","display_name":"[4Fe-4S] iron-sulfur cluster","entity_type_key":"chemical_species"},"role":"relevant cofactor class","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"da9d64bc-69d4-5d97-90a4-8f0ed03e0ac8","slug":"hydrogen-peroxide","display_name":"Hydrogen peroxide","entity_type_key":"small_molecule"},"role":"proposed injury mediator","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"4dc2faa3-f38c-5813-b7f2-fe19a0ab7bfa","slug":"respiratory-complex-ii","display_name":"Respiratory complex II","entity_type_key":"protein_complex"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Figure 6D","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"15 pmol/cell (approximately 8 mM) ascorbate for 1 h before activity assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. This pattern supports but does not by itself prove direct cluster oxidation; no organism-level mitochondrial benefit or harm claimed.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin C research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The exposure also impaired respiratory complex II, which participates in respiration and the citric acid cycle.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"NSCLC cell cultures","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f6db39d5-7d67-57ee-bbe3-66ffd3298778","evidence_kind":"source_excerpt","locator":"Lines 1383-1395","start_line":1383,"end_line":1395,"excerpt":"### c-reg-complex-ii-inactivation\nThe same pharmacological ascorbate exposure reduced NSCLC respiratory-complex II activity, extending the observed impairment to a second Fe-S-containing respiratory complex; complex IV activity was retained.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The exposure also impaired respiratory complex II, which participates in respiration and the citric acid cycle.\norganism: Homo sapiens\ntissue_or_cell_type: NSCLC cell cultures\nexperimental_model: Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays\nlimitations: Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. This pattern supports but does not by itself prove direct cluster oxidation; no organism-level mitochondrial benefit or harm claimed.\nexposure: 15 pmol/cell (approximately 8 mM) ascorbate for 1 h before activity assays.\ncross_nutrient: true\nevidence_location: Figure 6D\n[c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018","model_system":"Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"fa811221-13bd-5c10-adc1-eaf097c7703c","stable_key":"import-cb568d28-484a-5c2e-9fcc-2d780358e514","title":"Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"b7fd83f956abb81855f2ea23199ba14e465cd91f4a2ac560277ec21ddafd7bfc","revision_id":"6cde9bbb-d712-5746-82a6-85b144253efa","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}