{"doi":"10.1038/s41467-024-48151-1","title":"Structural basis for the intracellular regulation of ferritin degradation","abstract":"The interaction between nuclear receptor coactivator 4 (NCOA4) and the iron storage protein ferritin is a crucial component of cellular iron homeostasis. The binding of NCOA4 to the FTH1 subunits of ferritin initiates ferritinophagy-a ferritin-specific autophagic pathway leading to the release of the iron stored inside ferritin. The dysregulation of NCOA4 is associated with several diseases, including neurodegenerative disorders and cancer, highlighting the NCOA4-ferritin interface as a prime target for drug development. Here, we present the cryo-EM structure of the NCOA4-FTH1 interface, resolving 16 amino acids of NCOA4 that are crucial for the interaction. The characterization of mutants, designed to modulate the NCOA4-FTH1 interaction, is used to validate the significance of the different features of the binding site. Our results explain the role of the large solvent-exposed hydrophobic patch found on the surface of FTH1 and pave the way for the rational development of ferritinophagy modulators.","journal":"Nature Communications","year":2024,"id":417901,"datarank":0.6141516843333151,"base_score":4.0943445622221,"endowment":4.0943445622221,"self_citation_contribution":0.6141516843333151,"citation_network_contribution":0.0,"self_endowment_contribution":0.6141516843333151,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1204522,"name":"Thuy T. P. Nguyen","orcid":"0000-0002-3507-2309","position":1,"is_corresponding":false},{"id":1205146,"name":"Elina Klukin","orcid":null,"position":2,"is_corresponding":false},{"id":1204523,"name":"Mohamed Boumaiza","orcid":"0000-0001-7686-6722","position":3,"is_corresponding":false},{"id":676696,"name":"Ayush Srivastava","orcid":"0000-0003-1713-8893","position":4,"is_corresponding":false},{"id":1204524,"name":"Elizabeth Y. Kim","orcid":"0009-0000-2292-9302","position":5,"is_corresponding":false},{"id":736184,"name":"Ran Zalk","orcid":"0000-0003-4251-6497","position":6,"is_corresponding":false},{"id":1204525,"name":"Anat Shahar","orcid":"0000-0002-7287-2559","position":7,"is_corresponding":false},{"id":1204526,"name":"Sagit Cohen-Schwartz","orcid":"0000-0001-6251-0389","position":8,"is_corresponding":false},{"id":1174339,"name":"Esther G. Meyron‐Holtz","orcid":"0000-0003-4569-7975","position":9,"is_corresponding":false},{"id":500685,"name":"Fadi Bou‐Abdallah","orcid":"0000-0002-8557-1827","position":10,"is_corresponding":false},{"id":237057,"name":"Joseph D. Mancias","orcid":"0000-0002-0692-3717","position":11,"is_corresponding":false},{"id":1204527,"name":"Gabriel A. Frank","orcid":"0000-0001-8379-5133","position":12,"is_corresponding":false},{"id":1205145,"name":"Fabian Hoelzgen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:56:56.807779Z","pmid":"38714719","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":[]}