{"id":"8d610f82-a18f-5439-a116-f13b025edb23","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:mut0-kidney-parkin-recruitment","predicate":"loss-of-function-reduces","statement":"MMUT-deficient human kidney cells showed reduced Parkin recruitment after 5 micromolar rotenone for four hours.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"aedbd851-d39f-529d-87ae-587a828036dc","mechanism_event_label":"In this damage assay, patient kidney cells marked fewer mitochondria with Parkin.","subject":{"id":"7c1e45c3-bb73-5e63-8b3d-4bb3c96ed819","slug":"mmut-human-gene","display_name":"MMUT gene (Homo sapiens)","entity_type_key":"gene"},"object":{"id":"d3182857-c805-55ce-9607-7eae906fa66d","slug":"parkin-mitochondrial-recruitment","display_name":"Parkin recruitment to mitochondria","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"aedbd851-d39f-529d-87ae-587a828036dc","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:mut0-kidney-parkin-recruitment-event","event_type":"biochemical_relationship","label":"In this damage assay, patient kidney cells marked fewer mitochondria with Parkin.","description":"MMUT-deficient human kidney cells showed reduced Parkin recruitment after 5 micromolar rotenone for four hours.","status":"provisional","compartment":{"slug":"mitochondria","display_name":"Mitochondria"},"participants":[{"entity":{"id":"942dac3c-2e10-5d9b-a460-f048356936f4","slug":"prkn","display_name":"Human Parkin / PRKN","entity_type_key":"protein"},"role":"recruited-protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"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":1,"notes":""},{"entity":{"id":"d3182857-c805-55ce-9607-7eae906fa66d","slug":"parkin-mitochondrial-recruitment","display_name":"Parkin recruitment to mitochondria","entity_type_key":"cellular_process"},"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":"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 four 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. Endogenous PINK1 was not directly quantified.","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":"In this damage assay, patient kidney cells marked fewer mitochondria with Parkin.","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. (2020). https://pubmed.ncbi.nlm.nih.gov/32080200/ DOI: 10.1038/s41467-020-14729-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Kidney tubular cells","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":"9f242a0b-184c-52b0-a2e7-878b71739918","evidence_kind":"source_excerpt","locator":"Lines 1356-1368","start_line":1356,"end_line":1368,"excerpt":"### mut0-kidney-parkin-recruitment\nMMUT-deficient human kidney cells showed reduced Parkin recruitment after 5 micromolar rotenone for four hours.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: In this damage assay, patient kidney cells marked fewer mitochondria with Parkin.\norganism: Homo sapiens\ntissue_or_cell_type: Kidney tubular cells\nexperimental_model: Urine-derived human mut0 MMA kidney tubular cells\nlimitations: Inherited MMUT machinery defect; cannot be generalized to nutritional B12 deficiency or neurons. Endogenous PINK1 was not directly quantified.\nexposure: MMUT-inactivating genotypes plus 5 micromolar rotenone for four hours\ncross_nutrient: false\nevidence_location: Full text Results; Figures 2f,5c-f,6c-d\n[luciani-2020-mmut-mitophagy] Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency. (2020). https://pubmed.ncbi.nlm.nih.gov/32080200/ DOI: 10.1038/s41467-020-14729-8","model_system":"Urine-derived human mut0 MMA kidney tubular cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [luciani-2020-mmut-mitophagy] Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency. 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