{"id":"434872c4-0c7a-57fe-93fe-43835cfa611c","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-coa6-respiratory-loss","predicate":"loss_impairs","statement":"COA6 loss caused combined respiratory complex I and IV deficiency in human cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"8011e887-a584-5ae0-b3eb-e27865fd0c23","mechanism_event_label":"A failure in copper-enzyme assembly can affect more than one respiratory complex.","subject":{"id":"7ff2c8cb-50e2-5ac1-82d2-50a914b38a14","slug":"coa6","display_name":"Human cytochrome c oxidase assembly factor COA6","entity_type_key":"protein"},"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":"8011e887-a584-5ae0-b3eb-e27865fd0c23","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-coa6-respiratory-loss-event","event_type":"biochemical_relationship","label":"A failure in copper-enzyme assembly can affect more than one respiratory complex.","description":"COA6 loss caused combined respiratory complex I and IV deficiency in human cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f67ac698-de2e-55f5-8975-305eaadbb751","slug":"respiratory-complex-i","display_name":"Mitochondrial respiratory complex I","entity_type_key":"protein_complex"},"role":"additional affected complex","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7ff2c8cb-50e2-5ac1-82d2-50a914b38a14","slug":"coa6","display_name":"Human cytochrome c oxidase assembly factor COA6","entity_type_key":"protein"},"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/32061935.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a\", \"start_char\": 0, \"end_char\": 1043, \"text_sha256\": \"7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"COA6 knockout HEK293T cells and biochemical protein interaction experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"COA6 loss; SCO1/SCO2 disulfide reduction assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"COA6 machinery failure is not dietary copper depletion. 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Protein import effects were selective rather than universal loss of all mitochondrial import.\nexposure: COA6 loss; SCO1/SCO2 disulfide reduction assays\nevidence_span: {\"source_cache\": \"artifacts/copper-research/32061935.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a\", \"start_char\": 0, \"end_char\": 1043, \"text_sha256\": \"7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a\"}\n[copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. 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