{"id":"ff543f85-ba38-572b-b1dc-75abd7243cc9","stable_key":"6a5c5b4f-d859-5f43-ab2f-45c594a570ae:hri-loss-dfo-atf4","predicate":"has_contextual_experimental_effect","statement":"HRI knockdown suppressed iron-chelator-induced ISR activation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"098205e9-97eb-5b93-9364-744f951d10b7","mechanism_event_label":"hri loss dfo atf4","subject":{"id":"46de5cb6-4446-5560-803f-5b763d1d0186","slug":"human-hri-knockdown","display_name":"HRI knockdown in human cultured cells","entity_type_key":"protein_state"},"object":{"id":"1a9dd2b3-2552-5387-a086-66bea9f56058","slug":"atf4","display_name":"Human activating transcription factor 4 / ATF4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"098205e9-97eb-5b93-9364-744f951d10b7","stable_key":"6a5c5b4f-d859-5f43-ab2f-45c594a570ae:hri-loss-dfo-atf4","event_type":"experimental_result","label":"hri loss dfo atf4","description":"HRI knockdown suppressed iron-chelator-induced ISR activation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"46de5cb6-4446-5560-803f-5b763d1d0186","slug":"human-hri-knockdown","display_name":"HRI knockdown in human cultured cells","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1a9dd2b3-2552-5387-a086-66bea9f56058","slug":"atf4","display_name":"Human activating transcription factor 4 / ATF4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"279d00c2-a6a3-5943-8d5d-a7eed68e1041","slug":"deferoxamine","display_name":"Deferoxamine","entity_type_key":"drug"},"role":"exposure","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"access_level","value_text":"selected_indexed_full_text_passages","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_cache","value_text":"artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"HeLa","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"DFO/DFP; final 16 hours after 72-hour siRNA experiment","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human cultured cells; mouse xenograft host only for colonization endpoint","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"HRI knockdown suppressed iron-chelator-induced ISR activation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_locator","value_text":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 4G; S3C/D","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"https://doi.org/10.1016/j.molcel.2023.05.031","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"4ebc1e2f-c9f6-5f7b-ab48-942799c09188","evidence_kind":"source_excerpt","locator":"Lines 79-88","start_line":79,"end_line":88,"excerpt":"HRI knockdown suppressed iron-chelator-induced ISR activation.\nprimary_references: https://doi.org/10.1016/j.molcel.2023.05.031\nprimary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 4G; S3C/D\nevidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3\naccess_level: selected_indexed_full_text_passages\nexperimental_model: HeLa\norganism: Human cultured cells; mouse xenograft host only for colonization endpoint\nexposure: DFO/DFP; final 16 hours after 72-hour siRNA experiment\nlimitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.\nplain_language: HRI knockdown suppressed iron-chelator-induced ISR activation.","model_system":"HeLa","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Authored paraphrase; primary location and access limits retained.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"046f00ee-97ea-559c-b25f-7f73427fd72d","stable_key":"import-6a5c5b4f-d859-5f43-ab2f-45c594a570ae","title":"DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling","document_type":"imported_text","citation_label":"Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20.","file_path":"","sha256":"dbf79243751a179cadaaa833295cc4bdd0e617117e657c11eed25d7877267503","revision_id":"0218c622-6d40-5429-b03f-e5d2e1e67684","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}