{"id":"737522c6-81ad-51ba-8126-50cfc716af51","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-slc25a3-es-dlat","predicate":"increases_after_carrier_loss","statement":"Slc25a3-null rat cells exposed to elesclomol-copper showed increased DLAT oligomerization and loss of lipoylated DLAT and DLST.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2d7307f3-a349-55a2-8192-ad338855488c","mechanism_event_label":"Misplaced copper damaged proteins that normally carry lipoamide.","subject":{"id":"8ddc930e-bb4c-585e-b8bc-1e649853d76b","slug":"elesclomol-copper","display_name":"Elesclomol-copper complex","entity_type_key":"chemical_species"},"object":{"id":"6cc876a5-01a7-5e83-9db3-baac6a5b9939","slug":"rat-dlat-oligomerization","display_name":"Rat lipoylated Dlat oligomerization","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2d7307f3-a349-55a2-8192-ad338855488c","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-slc25a3-es-dlat-event","event_type":"biochemical_relationship","label":"Misplaced copper damaged proteins that normally carry lipoamide.","description":"Slc25a3-null rat cells exposed to elesclomol-copper showed increased DLAT oligomerization and loss of lipoylated DLAT and DLST.","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":"3c9a688d-6143-5a41-a63d-385ac8037ab0","slug":"rat-dlat","display_name":"Rat dihydrolipoamide S-acetyltransferase Dlat","entity_type_key":"protein"},"role":"affected lipoylated enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"10fdbc6a-8124-529e-813e-0923bc7b09a9","slug":"rat-dlst","display_name":"Rat dihydrolipoamide S-succinyltransferase Dlst","entity_type_key":"protein"},"role":"affected lipoylated enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"fd2197c3-5a63-55f4-8bb1-bfc1e91a0e1e","slug":"protein-bound-lipoamide","display_name":"Protein-bound oxidized lipoyl-lysine","entity_type_key":"chemical_species"},"role":"shared cofactor system","stoichiometry":null,"state_label":"","sequence_order":3,"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":4,"notes":""},{"entity":{"id":"6cc876a5-01a7-5e83-9db3-baac6a5b9939","slug":"rat-dlat-oligomerization","display_name":"Rat lipoylated Dlat oligomerization","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"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.fulltext.txt\", \"locator\": \"Exact primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0c19d3c109f1df88791ad51c22e6acf85b7d5ffe5c26c74aaaf5e3222a75c054\", \"start_char\": 5507, \"end_char\": 5866, \"text_sha256\": \"77f0d121a0aed5bdcd3c4898c369533a29208ebd8a9450a3a37ceff5d783c3af\"}","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":"Misplaced copper damaged proteins that normally carry lipoamide.","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. 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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.fulltext.txt\", \"locator\": \"Exact primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0c19d3c109f1df88791ad51c22e6acf85b7d5ffe5c26c74aaaf5e3222a75c054\", \"start_char\": 5507, \"end_char\": 5866, \"text_sha256\": \"77f0d121a0aed5bdcd3c4898c369533a29208ebd8a9450a3a37ceff5d783c3af\"}\n[copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. 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