{"id":"40828c20-3a67-54be-b92f-1485d29487ad","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:coa-import-joint","predicate":"decreases_in_recorded_comparison","statement":"Combined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"e3f8b3f8-b51b-502f-aa92-3553169539e2","mechanism_event_label":"Combined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells.","subject":{"id":"010f4333-18ae-50cb-8066-e42cf790b60e","slug":"human-slc25a16","display_name":"Human mitochondrial CoA transporter SLC25A16","entity_type_key":"protein"},"object":{"id":"94a217a9-2acb-5ce1-ae73-e7e7f024debd","slug":"human-mitochondrial-coash-pool","display_name":"Human-cell mitochondrial free CoASH pool","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e3f8b3f8-b51b-502f-aa92-3553169539e2","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:coa-import-joint-event","event_type":"experimental_observation","label":"Combined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells.","description":"### coa-import-joint\n\nCombined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells.\nLoss of both transporters also depleted several matrix-enriched short-chain acyl-CoAs. Stable-isotope CoASH uptake was reduced. Do not split this double-knockout result into two independent single-gene effects.\nModel and exposure: Human K562/HeLa double-knockout cells; mitochondrial isolation and LC-MS; Figs 4–7.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | 2025 | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"010f4333-18ae-50cb-8066-e42cf790b60e","slug":"human-slc25a16","display_name":"Human mitochondrial CoA transporter SLC25A16","entity_type_key":"protein"},"role":"tested factor","stoichiometry":null,"state_label":"SLC25A16 and SLC25A42 double knockout","sequence_order":0,"notes":""},{"entity":{"id":"94a217a9-2acb-5ce1-ae73-e7e7f024debd","slug":"human-mitochondrial-coash-pool","display_name":"Human-cell mitochondrial free CoASH pool","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""},{"entity":{"id":"14124a14-1eb8-5e7b-89d2-ad6ed3409238","slug":"slc25a42","display_name":"Human mitochondrial coenzyme A transporter SLC25A42","entity_type_key":"protein"},"role":"jointly deleted carrier","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"4faa6456-aff8-59eb-9e3f-3326a436e401","slug":"coenzyme-a","display_name":"Coenzyme A","entity_type_key":"small_molecule"},"role":"transported substrate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"deleted","comparator":"Matched control cells","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"human-slc25a16","display_name":"Human mitochondrial CoA transporter SLC25A16","entity_type_key":"protein"}},{"dimension":"experimental_condition","value_text":"deleted","comparator":"Matched control cells","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"slc25a42","display_name":"Human mitochondrial coenzyme A transporter SLC25A42","entity_type_key":"protein"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"SLC25A16 and SLC25A42 double knockout\", \"comparator\": \"Matched control cells\", \"endpoint\": \"Combined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells.\", \"effect_direction\": \"decrease\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"human-slc25a16\", \"state\": \"deleted\"}, {\"entity_slug\": \"slc25a42\", \"state\": \"deleted\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Human K562/HeLa double-knockout cells; mitochondrial isolation and LC-MS; Figs 4–7.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived curation with stated access limits; ungraded, not independent replication.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Combined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference coa-import-joint; Loss of both transporters also depleted several matrix-enriched short-chain acyl-CoAs. Stable-isotope CoASH uptake was reduced. Do not split this double-knockout result into two independent single-gene effects.","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":"aad2fa51-e5b5-57ec-a2a3-48baa68df29d","evidence_kind":"source_excerpt","locator":"Lines 60-66","start_line":60,"end_line":66,"excerpt":"### coa-import-joint\n\nCombined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells.\nLoss of both transporters also depleted several matrix-enriched short-chain acyl-CoAs. Stable-isotope CoASH uptake was reduced. Do not split this double-knockout result into two independent single-gene effects.\nModel and exposure: Human K562/HeLa double-knockout cells; mitochondrial isolation and LC-MS; Figs 4–7.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | 2025 | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","model_system":"Human K562/HeLa double-knockout cells; mitochondrial isolation and LC-MS; Figs 4–7.","directness":"reported_statement","verification_status":"source_recorded","notes":"Original paraphrase in the retained reviewed reference, not a verbatim primary-paper quotation. Access level is explicit.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"2588f904-245a-597a-8a12-65118013fb90","stable_key":"import-e3f6ce02-0bd7-5103-acc1-68503ab6751b","title":"Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026)","document_type":"imported_text","citation_label":"AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed.","file_path":"","sha256":"84cc82d6fbb0fd5d73c4ce779e9f88e7f0184ba2d29b18ad0f153815380f2975","revision_id":"dac7a950-dbe5-5c7a-9c70-2ea711d5c71a","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}