{"id":"ef572bc2-e774-5775-96df-72a5f3065202","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-mito-gshf-rescue","predicate":"improves","statement":"Targeted bacterial GshF enabled mitochondrial GSH synthesis and ameliorated proliferative defects.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"57fa914e-1406-5445-b04e-d3708cd6e13f","mechanism_event_label":"Producing glutathione inside mitochondria bypassed the import problem experimentally.","subject":{"id":"e2c0f70e-225d-5615-a8ab-64b145ad27af","slug":"mito-gshf-engineered","display_name":"Engineered mitochondrially targeted bacterial GshF in mammalian cells","entity_type_key":"protein"},"object":{"id":"727ab3c2-ec4d-573f-9bf3-c258b1275600","slug":"a39-cell-proliferation","display_name":"Proliferation of mitochondrial-GSH-depleted mammalian cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"57fa914e-1406-5445-b04e-d3708cd6e13f","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-mito-gshf-rescue-event","event_type":"biochemical_relationship","label":"Producing glutathione inside mitochondria bypassed the import problem experimentally.","description":"Targeted bacterial GshF enabled mitochondrial GSH synthesis and ameliorated proliferative defects.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e2c0f70e-225d-5615-a8ab-64b145ad27af","slug":"mito-gshf-engineered","display_name":"Engineered mitochondrially targeted bacterial GshF in mammalian cells","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"727ab3c2-ec4d-573f-9bf3-c258b1275600","slug":"a39-cell-proliferation","display_name":"Proliferation of mitochondrial-GSH-depleted mammalian cells","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":"evidence_span","value_text":"{\"source_cache\": \"artifacts/glutathione-research/34707288.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5\", \"start_char\": 0, \"end_char\": 1450, \"text_sha256\": \"7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Organelle metabolomics, genetics and targeted synthesis rescue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"SLC25A39 loss, A39/A40 double loss and targeted GshF","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation.","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":"Mammalian cells; separate mouse erythropoiesis experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Producing glutathione inside mitochondria bypassed the import problem experimentally.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. 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