{"id":"3007c190-fb7c-5527-a556-efe796dba011","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-slc25a3-es-no-cox-rescue","predicate":"fails_to_restore_after_carrier_loss","statement":"Elesclomol-copper increased mitochondrial copper but failed to restore COX1 abundance in rat Slc25a3-null cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"d388341b-e7d1-542f-b90c-c977cf49ce6c","mechanism_event_label":"Delivering more copper to the organelle did not ensure delivery to the enzyme.","subject":{"id":"8ddc930e-bb4c-585e-b8bc-1e649853d76b","slug":"elesclomol-copper","display_name":"Elesclomol-copper complex","entity_type_key":"chemical_species"},"object":{"id":"7a6f5c2d-cf51-5638-8d69-37355ca6f9d7","slug":"respiratory-complex-iv","display_name":"Mitochondrial cytochrome c oxidase / respiratory complex IV","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"d388341b-e7d1-542f-b90c-c977cf49ce6c","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-slc25a3-es-no-cox-rescue-event","event_type":"biochemical_relationship","label":"Delivering more copper to the organelle did not ensure delivery to the enzyme.","description":"Elesclomol-copper increased mitochondrial copper but failed to restore COX1 abundance in rat Slc25a3-null cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"55442aed-932d-595a-bbf9-a5006d0813e3","slug":"rat-slc25a3","display_name":"Rat mitochondrial phosphate/copper carrier Slc25a3","entity_type_key":"protein"},"role":"deleted carrier","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8ddc930e-bb4c-585e-b8bc-1e649853d76b","slug":"elesclomol-copper","display_name":"Elesclomol-copper complex","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7a6f5c2d-cf51-5638-8d69-37355ca6f9d7","slug":"respiratory-complex-iv","display_name":"Mitochondrial cytochrome c oxidase / respiratory complex IV","entity_type_key":"protein_complex"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"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/copper-research/42308035.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92\", \"start_char\": 0, \"end_char\": 1276, \"text_sha256\": \"a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Slc25a3 deletion and elesclomol-copper exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Copper research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Rat H9c2 cells; human SLC25A3 in Lactococcus lactis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Delivering more copper to the organelle did not ensure delivery to the enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Mitochondria; bacterial copper export assay","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":"17711e57-b5f0-5213-a36a-fc3da7b38a30","evidence_kind":"source_excerpt","locator":"Lines 559-570","start_line":559,"end_line":570,"excerpt":"### copper-slc25a3-es-no-cox-rescue\nElesclomol-copper increased mitochondrial copper but failed to restore COX1 abundance in rat Slc25a3-null cells.\nCondition category: machinery_impairment\nnutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Delivering more copper to the organelle did not ensure delivery to the enzyme.\norganism: Rat H9c2 cells; human SLC25A3 in Lactococcus lactis\ntissue_or_cell_type: Mitochondria; bacterial copper export assay\nexperimental_model: Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria\nlimitations: Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology.\nexposure: Slc25a3 deletion and elesclomol-copper exposure\nevidence_span: {\"source_cache\": \"artifacts/copper-research/42308035.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92\", \"start_char\": 0, \"end_char\": 1276, \"text_sha256\": \"a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92\"}\n[copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123","model_system":"Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"9afba495-cbdc-51aa-998e-70a930dba3be","stable_key":"import-0ad8610d-d575-5870-b7cd-763a9f750783","title":"Copper: transport, cuproenzymes, deficiency, excess 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. 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