{"id":"6ff04b4b-fac4-55fd-9550-b7edaac73e9c","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-a39-iron-oxphos","predicate":"interacts_functionally_with","statement":"A39-mediated GSH homeostasis and A37-mediated iron uptake jointly supported OXPHOS in the genetic-interaction system.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"22542843-f0c1-51f9-bdb6-42f382a7cc7f","mechanism_event_label":"Iron delivery and glutathione delivery met at mitochondrial energy production.","subject":{"id":"2b210ef5-c77e-57a3-be04-7876c67b8d75","slug":"slc25a39","display_name":"Human mitochondrial glutathione carrier SLC25A39","entity_type_key":"protein"},"object":{"id":"cd0bacf3-ff7b-5c9f-a2f0-bd06542bfaea","slug":"slc25a37","display_name":"Human mitoferrin-1 / SLC25A37","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"22542843-f0c1-51f9-bdb6-42f382a7cc7f","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-a39-iron-oxphos-event","event_type":"biochemical_relationship","label":"Iron delivery and glutathione delivery met at mitochondrial energy production.","description":"A39-mediated GSH homeostasis and A37-mediated iron uptake jointly supported OXPHOS in the genetic-interaction system.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b0b79651-8ed3-5bd6-935b-d46680df3671","slug":"a39-a37-oxphos","display_name":"Oxidative phosphorylation in the SLC25A39/SLC25A37 genetic-interaction system","entity_type_key":"cellular_process"},"role":"measured_outcome","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2b210ef5-c77e-57a3-be04-7876c67b8d75","slug":"slc25a39","display_name":"Human mitochondrial glutathione carrier SLC25A39","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"cd0bacf3-ff7b-5c9f-a2f0-bd06542bfaea","slug":"slc25a37","display_name":"Human mitoferrin-1 / SLC25A37","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/glutathione-research/35513392.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7\", \"start_char\": 0, \"end_char\": 1457, \"text_sha256\": \"000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Paired CRISPR screen and mitochondrial transport assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"2016 single/pair perturbations across four metabolic states","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Genetic buffering depends on metabolic conditions; it is not evidence that iron supplementation corrects low GSH.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Glutathione research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human experimental cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Iron delivery and glutathione delivery met at mitochondrial energy production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[glutathione-p35513392] Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. (2022). https://pubmed.ncbi.nlm.nih.gov/35513392/ DOI: 10.1038/s41467-022-30126-9","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Mitochondrial transport and respiration","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ddc6c54e-283f-5a5d-983f-9f2c63d56841","evidence_kind":"source_excerpt","locator":"Lines 528-539","start_line":528,"end_line":539,"excerpt":"### glutathione-a39-iron-oxphos\nA39-mediated GSH homeostasis and A37-mediated iron uptake jointly supported OXPHOS in the genetic-interaction system.\nCondition category: normal\nnutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Iron delivery and glutathione delivery met at mitochondrial energy production.\norganism: Human experimental cells\ntissue_or_cell_type: Mitochondrial transport and respiration\nexperimental_model: Paired CRISPR screen and mitochondrial transport assays\nlimitations: Genetic buffering depends on metabolic conditions; it is not evidence that iron supplementation corrects low GSH.\nexposure: 2016 single/pair perturbations across four metabolic states\nevidence_span: {\"source_cache\": \"artifacts/glutathione-research/35513392.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7\", \"start_char\": 0, \"end_char\": 1457, \"text_sha256\": \"000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7\"}\n[glutathione-p35513392] Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. 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