{"id":"9eb3db50-9f07-53c1-80b4-d3c8eab51298","stable_key":"066fc1e8-fefc-5be0-9905-938b10b89691:hmox2-k68r-mito-iron","predicate":"has_contextual_experimental_effect","statement":"K68R HMOX2 re-expression failed to restore mitochondrial iron as wild-type HMOX2 did in HMOX2-knockout HeLa cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"8e2e7c7b-0c01-535e-812a-a444e9f89f4a","mechanism_event_label":"hmox2 k68r mito iron","subject":{"id":"98e5c0b8-3037-5b89-80c8-fe9f86d4b91d","slug":"human-hmox2-k68r-rescue-hela","display_name":"K68R HMOX2 re-expression in HMOX2-null HeLa cells","entity_type_key":"protein_state"},"object":{"id":"e2084fd0-e763-5b6a-bf64-f4010a8442d4","slug":"human-mitochondrial-total-iron","display_name":"Total iron in isolated human-cell mitochondria","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"8e2e7c7b-0c01-535e-812a-a444e9f89f4a","stable_key":"066fc1e8-fefc-5be0-9905-938b10b89691:hmox2-k68r-mito-iron","event_type":"experimental_result","label":"hmox2 k68r mito iron","description":"K68R HMOX2 re-expression failed to restore mitochondrial iron as wild-type HMOX2 did in HMOX2-knockout HeLa cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"98e5c0b8-3037-5b89-80c8-fe9f86d4b91d","slug":"human-hmox2-k68r-rescue-hela","display_name":"K68R HMOX2 re-expression in HMOX2-null HeLa cells","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e2084fd0-e763-5b6a-bf64-f4010a8442d4","slug":"human-mitochondrial-total-iron","display_name":"Total iron in isolated human-cell mitochondria","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"role":"measured element","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d1b04cde-2e03-5ec6-ae2c-f90889cf4561","slug":"human-hmox2-knockout-hela","display_name":"HMOX2 knockout in HeLa cells","entity_type_key":"protein_state"},"role":"experimental background","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"access_level","value_text":"selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_cache","value_text":"artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"HeLa; MERBiT reporter derivative where stated","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Stable re-expression in HMOX2 KO clone 1; ICP-MS total iron; comparison with wild-type re-expression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_locator","value_text":"Figure 4f","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"https://doi.org/10.1038/s41556-026-01974-0","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d9732696-8a35-51ea-96ac-27c262e5196c","evidence_kind":"source_excerpt","locator":"Lines 72-80","start_line":72,"end_line":80,"excerpt":"K68R HMOX2 re-expression failed to restore mitochondrial iron as wild-type HMOX2 did in HMOX2-knockout HeLa cells.\nprimary_references: https://doi.org/10.1038/s41556-026-01974-0\nprimary_locator: Figure 4f\nevidence_cache: artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a\naccess_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review\norganism: Human\nexperimental_model: HeLa; MERBiT reporter derivative where stated\nexposure: Stable re-expression in HMOX2 KO clone 1; ICP-MS total iron; comparison with wild-type re-expression\nlimitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.","model_system":"Human HeLa cells","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Authored paraphrase with primary location; not a publisher quotation.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"e52836df-b22a-51c4-9ab4-6b258a554969","stable_key":"import-066fc1e8-fefc-5be0-9905-938b10b89691","title":"Glutathione, ER-mitochondria contacts, and iron: observed components","document_type":"imported_text","citation_label":"Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0.","file_path":"","sha256":"381747aa54ebbd40dfc3d830264e0231a09c3e417ad896a591dffc10dcdc64f4","revision_id":"d679b06d-a889-5aba-b69b-f5c07d393c24","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}