{"id":"f67c4012-7bb4-5c2a-a074-0133f122818c","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-coa6-protein-import","predicate":"loss_impairs","statement":"COA6 loss reduced membrane potential and impaired potential-dependent protein import across the inner mitochondrial membrane.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"29692356-f402-5431-a23f-1aa4ecfe7da9","mechanism_event_label":"The energy deficit can interfere with importing other mitochondrial proteins.","subject":{"id":"7ff2c8cb-50e2-5ac1-82d2-50a914b38a14","slug":"coa6","display_name":"Human cytochrome c oxidase assembly factor COA6","entity_type_key":"protein"},"object":{"id":"435c3ff4-c8c2-56f9-b388-4f97e0525efc","slug":"membrane-potential-dependent-mitochondrial-import","display_name":"Membrane-potential-dependent mitochondrial protein import","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"29692356-f402-5431-a23f-1aa4ecfe7da9","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-coa6-protein-import-event","event_type":"biochemical_relationship","label":"The energy deficit can interfere with importing other mitochondrial proteins.","description":"COA6 loss reduced membrane potential and impaired potential-dependent protein import across the inner mitochondrial membrane.","status":"provisional","compartment":null,"participants":[{"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":0,"notes":""},{"entity":{"id":"435c3ff4-c8c2-56f9-b388-4f97e0525efc","slug":"membrane-potential-dependent-mitochondrial-import","display_name":"Membrane-potential-dependent mitochondrial protein import","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"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. Protein import effects were selective rather than universal loss of all mitochondrial import.","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":"Human cells and proteins","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The energy deficit can interfere with importing other mitochondrial proteins.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Mitochondrial intermembrane space","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":"de477e33-ad42-500c-a7c9-f934fab7498d","evidence_kind":"source_excerpt","locator":"Lines 689-700","start_line":689,"end_line":700,"excerpt":"### copper-coa6-protein-import\nCOA6 loss reduced membrane potential and impaired potential-dependent protein import across the inner mitochondrial membrane.\nCondition category: machinery_impairment\nnutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The energy deficit can interfere with importing other mitochondrial proteins.\norganism: Human cells and proteins\ntissue_or_cell_type: Mitochondrial intermembrane space\nexperimental_model: COA6 knockout HEK293T cells and biochemical protein interaction experiments\nlimitations: COA6 machinery failure is not dietary copper depletion. 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. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036","model_system":"COA6 knockout HEK293T cells and biochemical protein interaction experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036","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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