{"id":"43c2f5a4-1338-5265-9563-273328bc09ad","stable_key":"4fef8d72-f107-5eb5-b2fb-483ca85465e0:k2-fsp1-gpx4-parallel","predicate":"loss_with_gpx4_loss_increases_requirement_for","statement":"Cells lacking both GPX4 and FSP1 required higher K1/MK-4 concentrations to prevent ferroptosis than cells lacking GPX4 alone.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4a8f1bdb-daad-5af6-a37c-16bf51ff547b","mechanism_event_label":"The FSP1 pathway and selenium-dependent GPX4 defense are connected but not the same mechanism.","subject":{"id":"6c60c705-b3dc-548d-a2ad-e9f75249a642","slug":"aifm2","display_name":"FSP1 / AIFM2","entity_type_key":"protein"},"object":{"id":"5155b9d1-e835-54b4-9f61-4cf35b3e5227","slug":"menaquinone-4","display_name":"Menaquinone-4 / MK-4 / menatetrenone","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"4a8f1bdb-daad-5af6-a37c-16bf51ff547b","stable_key":"4fef8d72-f107-5eb5-b2fb-483ca85465e0:k2-fsp1-gpx4-parallel-event","event_type":"biochemical_relationship","label":"The FSP1 pathway and selenium-dependent GPX4 defense are connected but not the same mechanism.","description":"Cells lacking both GPX4 and FSP1 required higher K1/MK-4 concentrations to prevent ferroptosis than cells lacking GPX4 alone.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"role":"parallel_defense","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5f9fd13b-5428-5024-a855-9db526855890","slug":"phylloquinone","display_name":"Phylloquinone","entity_type_key":"small_molecule"},"role":"other_tested_form","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6c60c705-b3dc-548d-a2ad-e9f75249a642","slug":"aifm2","display_name":"FSP1 / AIFM2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5155b9d1-e835-54b4-9f61-4cf35b3e5227","slug":"menaquinone-4","display_name":"Menaquinone-4 / MK-4 / menatetrenone","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"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/k2-research/35922516.fulltext.txt\", \"locator\": \"Exact primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a75e4881732cbe87173197db393b42d49fc6e8110df919fed8d63b16c9877da6\", \"start_char\": 16083, \"end_char\": 16259, \"text_sha256\": \"942e81f7fca3a59aecc9d6cfcdc008e88931de54074e63eeb96c71af3d236eec\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"MK-4/K1, NAD(P)H, FSP1 loss and inhibitors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"k2","display_name":"Vitamin K2 / menaquinone family","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human recombinant FSP1, mammalian cells and mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The FSP1 pathway and selenium-dependent GPX4 defense are connected but not the same mechanism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Lipid peroxidation and vitamin K reduction","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":"76819d8d-becc-5ad0-ba64-d536d0b93ff0","evidence_kind":"source_excerpt","locator":"Lines 812-823","start_line":812,"end_line":823,"excerpt":"### k2-fsp1-gpx4-parallel\nCells lacking both GPX4 and FSP1 required higher K1/MK-4 concentrations to prevent ferroptosis than cells lacking GPX4 alone.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The FSP1 pathway and selenium-dependent GPX4 defense are connected but not the same mechanism.\norganism: Human recombinant FSP1, mammalian cells and mice\ntissue_or_cell_type: Lipid peroxidation and vitamin K reduction\nexperimental_model: Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice\nlimitations: Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning.\nexposure: MK-4/K1, NAD(P)H, FSP1 loss and inhibitors\nevidence_span: {\"source_cache\": \"artifacts/k2-research/35922516.fulltext.txt\", \"locator\": \"Exact primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a75e4881732cbe87173197db393b42d49fc6e8110df919fed8d63b16c9877da6\", \"start_char\": 16083, \"end_char\": 16259, \"text_sha256\": \"942e81f7fca3a59aecc9d6cfcdc008e88931de54074e63eeb96c71af3d236eec\"}\n[k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3","model_system":"Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dfeae572-af3d-5042-a10e-e67596f9ab28","stable_key":"import-4fef8d72-f107-5eb5-b2fb-483ca85465e0","title":"Vitamin K2: menaquinone forms, carboxylation, recycling 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":"dc31aff21110d09b025c177e03b4c5ca8349d52bf5f962285fdbfcf660c0e4f6","revision_id":"850887db-34f6-55aa-9d3e-b8fd3a4a5de3","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}