{"id":"61b744ff-3943-52b4-90f6-14343f125d8c","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-ncoa4-ferritin","predicate":"mediates","statement":"NCOA4 associated with ferritin heavy/light chains and was required for their delivery to lysosomes.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ab651bcf-a156-5bfa-8ed0-101e9ec1dc7a","mechanism_event_label":"A selective cargo receptor sends stored iron for release when cells need it.","subject":{"id":"8e4066eb-71c5-5408-974a-0d2451590487","slug":"ncoa4","display_name":"Human nuclear receptor coactivator 4 / NCOA4","entity_type_key":"protein"},"object":{"id":"028fd59a-f1e7-5d5f-b601-3eed3523d3c4","slug":"ferritin-lysosomal-delivery","display_name":"Lysosomal delivery and degradation of ferritin","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ab651bcf-a156-5bfa-8ed0-101e9ec1dc7a","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-ncoa4-ferritin-event","event_type":"biochemical_relationship","label":"A selective cargo receptor sends stored iron for release when cells need it.","description":"NCOA4 associated with ferritin heavy/light chains and was required for their delivery to lysosomes.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"05e98c8a-c341-5856-971a-5a7001db7fed","slug":"fth1","display_name":"Ferritin heavy chain","entity_type_key":"protein"},"role":"cargo_component","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"49a7bb74-d48a-5ab8-969d-785c2a2e9655","slug":"ftl","display_name":"Human ferritin light chain / FTL","entity_type_key":"protein"},"role":"cargo_component","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"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":2,"notes":""},{"entity":{"id":"028fd59a-f1e7-5d5f-b601-3eed3523d3c4","slug":"ferritin-lysosomal-delivery","display_name":"Lysosomal delivery and degradation of ferritin","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"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":"A selective cargo receptor sends stored iron for release when cells need it.","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}],"evidence":[{"id":"2f64bccd-4141-5a6a-ace5-148f24fec75d","evidence_kind":"source_excerpt","locator":"Lines 641-652","start_line":641,"end_line":652,"excerpt":"### iron-ncoa4-ferritin\nNCOA4 associated with ferritin heavy/light chains and was required for their delivery to lysosomes.\nCondition category: normal\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A selective cargo receptor sends stored iron for release when cells need it.\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. (2014). https://pubmed.ncbi.nlm.nih.gov/24695223/ DOI: 10.1038/nature13148","model_system":"Quantitative proteomics and selective-autophagy experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [iron-p24695223] Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. (2014). https://pubmed.ncbi.nlm.nih.gov/24695223/ DOI: 10.1038/nature13148","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"1560864c-91d1-58dc-90c4-49bf61aba3de","stable_key":"import-e13b03e1-a614-543a-ac1b-97df18cfe30d","title":"Iron: absorption, trafficking, iron-dependent enzymes 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":"f9dab767a21c9bbfef3227707fe3c82953536bb1335599dd4ef93b5ea2dbf03f","revision_id":"77700d7f-2902-54b9-adae-8cbc77b24682","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}