{"id":"e9974418-eccd-5336-9206-741b2cdc4873","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:mut0-kidney-impaired-mito-delivery","predicate":"loss-of-function-reduces","statement":"MMUT-deficient human kidney cells failed to show the control mt-Keima lysosomal shift after 24 hours of 5 micromolar rotenone.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ca6bbcb5-194e-5a80-a986-2cc7c9af29a9","mechanism_event_label":"After experimental mitochondrial damage, these patient kidney cells delivered fewer mitochondria to lysosomes.","subject":{"id":"7c1e45c3-bb73-5e63-8b3d-4bb3c96ed819","slug":"mmut-human-gene","display_name":"MMUT gene (Homo sapiens)","entity_type_key":"gene"},"object":{"id":"5bca5011-4ac9-5414-a394-b0314165a221","slug":"mitochondrial-lysosomal-delivery","display_name":"Mitochondrial delivery to lysosomes","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ca6bbcb5-194e-5a80-a986-2cc7c9af29a9","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:mut0-kidney-impaired-mito-delivery-event","event_type":"biochemical_relationship","label":"After experimental mitochondrial damage, these patient kidney cells delivered fewer mitochondria to lysosomes.","description":"MMUT-deficient human kidney cells failed to show the control mt-Keima lysosomal shift after 24 hours of 5 micromolar rotenone.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7c1e45c3-bb73-5e63-8b3d-4bb3c96ed819","slug":"mmut-human-gene","display_name":"MMUT gene (Homo sapiens)","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5bca5011-4ac9-5414-a394-b0314165a221","slug":"mitochondrial-lysosomal-delivery","display_name":"Mitochondrial delivery to lysosomes","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":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Full text Results; Figures 2f,5c-f,6c-d","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Urine-derived human mut0 MMA kidney tubular cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"MMUT-inactivating genotypes plus 5 micromolar rotenone for 24 hours","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Inherited MMUT machinery defect; cannot be generalized to nutritional B12 deficiency or neurons. mt-Keima is a delivery reporter.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"After experimental mitochondrial damage, these patient kidney cells delivered fewer mitochondria to lysosomes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[luciani-2020-mmut-mitophagy] Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency. 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