{"id":"7bc65c8a-e30e-503a-b153-a68d698b6a8f","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:transport-slc25a32-folate-uptake-preserved","predicate":"not-required-in-tested-assay-for","statement":"Slc25a32 mutant and knockout mitochondrial preparations retained folate-substrate uptake in the 2022 mouse study.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"479000ef-d77d-5b63-bec1-6be704fe4e72","mechanism_event_label":"The mouse experiments attributed the primary import defect to FAD, with folate uptake preserved.","subject":{"id":"62f38e8e-01cb-5e3e-b806-8c5aa333694f","slug":"mouse-slc25a32","display_name":"Mouse Slc25a32 mitochondrial carrier","entity_type_key":"protein"},"object":{"id":"8c8b4582-9980-54e3-a9ef-b07b16d97f94","slug":"mitochondrial-folate-uptake","display_name":"Mitochondrial folate uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"479000ef-d77d-5b63-bec1-6be704fe4e72","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:transport-slc25a32-folate-uptake-preserved-event","event_type":"biochemical_relationship","label":"The mouse experiments attributed the primary import defect to FAD, with folate uptake preserved.","description":"Slc25a32 mutant and knockout mitochondrial preparations retained folate-substrate uptake in the 2022 mouse study.","status":"provisional","compartment":{"slug":"mitochondria","display_name":"Mitochondria"},"participants":[{"entity":{"id":"62f38e8e-01cb-5e3e-b806-8c5aa333694f","slug":"mouse-slc25a32","display_name":"Mouse Slc25a32 mitochondrial carrier","entity_type_key":"protein"},"role":"affected-carrier","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d322bfef-5135-599f-82e6-0aa58748dc8b","slug":"folic-acid","display_name":"Folic acid","entity_type_key":"small_molecule"},"role":"tested-folate-substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8c8b4582-9980-54e3-a9ef-b07b16d97f94","slug":"mitochondrial-folate-uptake","display_name":"Mitochondrial folate uptake","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":"Separates primary flavin import from secondary folate-pool changes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Abstract and folate-uptake experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Folate uptake in genetically altered isolated mitochondria","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Labeled folic acid or 5-formyltetrahydrofolate in mitochondrial uptake assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Preserved uptake in this model does not fully resolve older human-cDNA complementation results.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Riboflavin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The mouse experiments attributed the primary import defect to FAD, with folate uptake preserved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Muscle and embryonic mitochondria","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":"617c6d5f-6fdd-58d6-beb1-5694a7fda48c","evidence_kind":"source_excerpt","locator":"Lines 516-528","start_line":516,"end_line":528,"excerpt":"### transport-slc25a32-folate-uptake-preserved\nSlc25a32 mutant and knockout mitochondrial preparations retained folate-substrate uptake in the 2022 mouse study.\nCondition category: machinery_impairment\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The mouse experiments attributed the primary import defect to FAD, with folate uptake preserved.\norganism: Mus musculus\ntissue_or_cell_type: Muscle and embryonic mitochondria\nexperimental_model: Folate uptake in genetically altered isolated mitochondria\nlimitations: Preserved uptake in this model does not fully resolve older human-cDNA complementation results.\nexposure: Labeled folic acid or 5-formyltetrahydrofolate in mitochondrial uptake assays.\ncross_nutrient: Separates primary flavin import from secondary folate-pool changes.\nevidence_location: Abstract and folate-uptake experiments\n[transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0","model_system":"Folate uptake in genetically altered isolated mitochondria","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f7c9578-82bf-5e2d-b5c4-72a79fb4f6af","stable_key":"import-548ab9d6-3a9b-5bed-879c-17d03813b636","title":"Riboflavin: mechanisms, deficiency 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. Not publisher full text.","file_path":"","sha256":"680cb6bc8249877f2410f551807f10d390fdd719014137d7414ba3420e29228d","revision_id":"7a61e299-908d-5372-860b-99ed190f9d7a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"e78de986-3c6e-58b9-a88c-626323c30589","title":"Does SLC25A32 directly import folate or support folate pools through FAD supply?","kind":"contradiction","status":"open","why":"The original human-cDNA complementation study interpreted SLC25A32 as a mitochondrial folate carrier; the later mouse study reported preserved folate uptake despite impaired FAD uptake and interpreted it primarily as an FAD carrier.","resolution":"Keep both observations and distinguish metabolic complementation from organelle substrate uptake. Purified human-carrier reconstitution, counter-substrate and stoichiometry remain unresolved by these two studies.","created_at":"2026-09-17 10:23:30","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/e78de986-3c6e-58b9-a88c-626323c30589","sides":[{"conflict_id":"e78de986-3c6e-58b9-a88c-626323c30589","ordinal":0,"label":"Folate accumulation rescued by human cDNA","revision_id":"7a61e299-908d-5372-860b-99ed190f9d7a","start_line":530,"end_line":542,"quote":"### transport-slc25a32-historical-folate-rescue\nHuman SLC25A32 cDNA restored mitochondrial folate accumulation and complemented glycine auxotrophy in CHO glyB cells, supporting the original folate-carrier interpretation.\nCondition category: machinery_impairment\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Early rescue experiments linked this carrier to mitochondrial folate availability.\norganism: Human cDNA in Cricetulus griseus cells\ntissue_or_cell_type: Cultured CHO glyB cells\nexperimental_model: Human placental cDNA complementation of CHO glyB cells\nlimitations: Steady-state accumulation and growth rescue do not distinguish direct folate transport from indirect metabolic rescue.\nexposure: Retroviral human cDNA and subcloned cDNA expression.\ncross_nutrient: Historical vitamin B9 interpretation of a carrier now implicated in vitamin B2 cofactor supply.\nevidence_location: Abstract; complementation and mitochondrial folate accumulation\n[transport-slc25a32-2000] Retrovirally mediated complementation of the glyB phenotype. Cloning of a human gene encoding the carrier for entry of folates into mitochondria. (2000). https://pubmed.ncbi.nlm.nih.gov/10978331/ DOI: 10.1074/jbc.M005163200","source_key":"import-548ab9d6-3a9b-5bed-879c-17d03813b636","source_title":"Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)","claim_ids":["36617b65-4c71-52ff-b4d1-d5d65a1178b9"]},{"conflict_id":"e78de986-3c6e-58b9-a88c-626323c30589","ordinal":1,"label":"Mouse folate uptake preserved while FAD uptake fails","revision_id":"7a61e299-908d-5372-860b-99ed190f9d7a","start_line":516,"end_line":528,"quote":"### transport-slc25a32-folate-uptake-preserved\nSlc25a32 mutant and knockout mitochondrial preparations retained folate-substrate uptake in the 2022 mouse study.\nCondition category: machinery_impairment\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The mouse experiments attributed the primary import defect to FAD, with folate uptake preserved.\norganism: Mus musculus\ntissue_or_cell_type: Muscle and embryonic mitochondria\nexperimental_model: Folate uptake in genetically altered isolated mitochondria\nlimitations: Preserved uptake in this model does not fully resolve older human-cDNA complementation results.\nexposure: Labeled folic acid or 5-formyltetrahydrofolate in mitochondrial uptake assays.\ncross_nutrient: Separates primary flavin import from secondary folate-pool changes.\nevidence_location: Abstract and folate-uptake experiments\n[transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0","source_key":"import-548ab9d6-3a9b-5bed-879c-17d03813b636","source_title":"Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)","claim_ids":["7bc65c8a-e30e-503a-b153-a68d698b6a8f"]}]}],"corrections":[],"research":null}