{"id":"51a8676a-ae3e-5470-a4fb-ac54e672c3ef","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-ncoa4-loss","predicate":"loss_reduced","statement":"NCOA4-deficient cells could not degrade ferritin normally and had decreased bioavailable intracellular iron.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"cca3d79a-e341-5666-801d-40ceb8cbba19","mechanism_event_label":"The cell could have iron in a storage cage while still lacking usable iron.","subject":{"id":"8e4066eb-71c5-5408-974a-0d2451590487","slug":"ncoa4","display_name":"Human nuclear receptor coactivator 4 / NCOA4","entity_type_key":"protein"},"object":{"id":"d1a76588-8d56-5ba9-9fd1-16a82dc52b94","slug":"labile-cellular-iron","display_name":"Cellular labile iron pool","entity_type_key":"chemical_species"},"evidence_count":1,"mechanism_event":{"id":"cca3d79a-e341-5666-801d-40ceb8cbba19","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-ncoa4-loss-event","event_type":"biochemical_relationship","label":"The cell could have iron in a storage cage while still lacking usable iron.","description":"NCOA4-deficient cells could not degrade ferritin normally and had decreased bioavailable intracellular iron.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8e4066eb-71c5-5408-974a-0d2451590487","slug":"ncoa4","display_name":"Human nuclear receptor coactivator 4 / NCOA4","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d1a76588-8d56-5ba9-9fd1-16a82dc52b94","slug":"labile-cellular-iron","display_name":"Cellular labile iron pool","entity_type_key":"chemical_species"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iron-research/24695223.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a\", \"start_char\": 0, \"end_char\": 1514, \"text_sha256\": \"ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Quantitative proteomics and selective-autophagy experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"NCOA4 association and loss experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Ferritinophagy supplies intracellular iron; it is not equivalent to serum ferritin concentration.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iron research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human cultured cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The cell could have iron in a storage cage while still lacking usable iron.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iron-p24695223] Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. (2014). https://pubmed.ncbi.nlm.nih.gov/24695223/ DOI: 10.1038/nature13148","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Autophagosomes and lysosomes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"fc924ea2-9be6-554c-bbc5-fedf26070ae1","evidence_kind":"source_excerpt","locator":"Lines 654-665","start_line":654,"end_line":665,"excerpt":"### iron-ncoa4-loss\nNCOA4-deficient cells could not degrade ferritin normally and had decreased bioavailable intracellular iron.\nCondition category: machinery_impairment\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The cell could have iron in a storage cage while still lacking usable iron.\norganism: Human cultured cells\ntissue_or_cell_type: Autophagosomes and lysosomes\nexperimental_model: Quantitative proteomics and selective-autophagy experiments\nlimitations: Ferritinophagy supplies intracellular iron; it is not equivalent to serum ferritin concentration.\nexposure: NCOA4 association and loss experiments\nevidence_span: {\"source_cache\": \"artifacts/iron-research/24695223.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a\", \"start_char\": 0, \"end_char\": 1514, \"text_sha256\": \"ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a\"}\n[iron-p24695223] Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. 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