{"id":"a647c3d5-c7cd-5fee-adfc-8780bb1cc65a","stable_key":"research:fsp1-parallel","predicate":"regenerates","statement":"FSP1 reduces CoQ and supplies a lipid-radical defense operating in parallel with GPX4.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"literature_reviewed:direct_experimental","direction":"positive","is_public":true,"mechanism_event_id":"f828e1e9-a8ae-5319-85e4-5af7ea1f63d2","mechanism_event_label":"Another defense changes how vulnerable cells are to GPX4 loss.","subject":{"id":"11b08385-45ff-564b-851f-e604582dcc8a","slug":"fsp1","display_name":"FSP1","entity_type_key":"protein"},"object":{"id":"64fbe9b3-bf24-5b66-9611-8b78262d6ffc","slug":"reduced-coq10","display_name":"Reduced CoQ10","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"f828e1e9-a8ae-5319-85e4-5af7ea1f63d2","stable_key":"research:fsp1-parallel","event_type":"redox_reaction","label":"Another defense changes how vulnerable cells are to GPX4 loss.","description":"FSP1 reduces CoQ and supplies a lipid-radical defense operating in parallel with GPX4.","status":"active","compartment":null,"participants":[{"entity":{"id":"11b08385-45ff-564b-851f-e604582dcc8a","slug":"fsp1","display_name":"FSP1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"64fbe9b3-bf24-5b66-9611-8b78262d6ffc","slug":"reduced-coq10","display_name":"Reduced CoQ10","entity_type_key":"small_molecule"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"cell_type","value_text":"Experimental cultured cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cell genetics and biochemical experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Capacity and dependence vary by cell; not a universal dietary threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human cell models","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9990f3bf-8ee3-54a1-b006-78863a75db1d","evidence_kind":"curated_literature_summary","locator":"lines 1492-1502","start_line":1492,"end_line":1502,"excerpt":"## fsp1-parallel\n\nAnother defense changes how vulnerable cells are to GPX4 loss.\n\nFSP1 reduces CoQ and supplies a lipid-radical defense operating in parallel with GPX4.\n\nOrganism: Human cell models\nCell type: Experimental cultured cells\nExperimental model: Cell genetics and biochemical experiments\nLimitations: Capacity and dependence vary by cell; not a universal dietary threshold.\nPrimary reference: [The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis](https://www.nature.com/articles/s41586-019-1705-2)","model_system":"Cell genetics and biochemical experiments","directness":"author_interpretation","verification_status":"secondary_verified","notes":"Curated summary; inspect the linked primary papers for original methods and results.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f892f13-06ea-5199-a33c-a703f35c80ae","stable_key":"selenium-research-2026-09-17","title":"Selenium: literature corrections and mechanism additions","document_type":"curated_literature_review","citation_label":"Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually","file_path":"","sha256":"0b818b10c1c7120e5caf7f4d4019d7bd025d745692e424f515d3ef903c9ab7f3","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","review_status":"secondary_verified","notes":"Secondary curated summaries of primary experiments, with explicit models and limitations. Not archived primary full text."}}],"relations":[],"conflicts":[],"corrections":[{"id":"37492085-76af-53f1-876b-6f036840dab5","title":"GPX4 impairment does not make ferroptosis unconditional","kind":"qualification","status":"qualified","why":"The earlier molecular passage gives a direct GPX4 loss or selenium starvation to membrane rupture cascade. The new reference adds parallel FSP1–CoQ10 defense and other contributors.","resolution":"Present GPX4 as central to phospholipid peroxide control while making the outcome conditional on the cell and its other defenses. The older correction draft also already describes parallel axes; this qualification targets the unconditional molecular wording.","created_at":"2026-09-17 05:59:32","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/37492085-76af-53f1-876b-6f036840dab5","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1591,"end_line":1596,"papers":[{"paper_key":"bersuker-2019","title":"The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis","url":"https://www.nature.com/articles/s41586-019-1705-2","doi":"10.1038/s41586-019-1705-2","year":2019,"model":"Cell genetics and biochemical experiments","summary":"FSP1/CoQ provides parallel lipid-radical defense."}]},"sides":[{"conflict_id":"37492085-76af-53f1-876b-6f036840dab5","ordinal":0,"label":"Earlier statement","revision_id":"1fa1ebde-141f-5d47-8a4f-ba87ff84a6c6","start_line":89,"end_line":91,"quote":"**Cascade into ferroptosis:**\n\nPUFA (arachidonoyl) → **ACSL4** → esterified into PE → **LPCAT3** → **ALOX15** or Fe²⁺-driven autoxidation → **PE-AA-OOH** in the membrane → GPX4 reduces it to PE-AA-OH. Knock out GPX4, drug it (RSL3, ML162 — which covalently alkylate the selenolate *because* it's the best nucleophile around), or starve it of Se → hydroperoxides propagate → membrane rupture → ferroptosis.","claim_id":null,"source_key":"molecular","source_title":"Selenium: the molecular cascade","claim_ids":[]},{"conflict_id":"37492085-76af-53f1-876b-6f036840dab5","ordinal":1,"label":"New reference qualification","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","start_line":119,"end_line":123,"quote":"Why GPX4 is especially important\n\nGPX4 directly reduces phospholipid hydroperoxides in membranes and is a central suppressor of ferroptosis. Severe loss of GPX4 function can therefore have consequences very different from loss of a more dispensable peroxide-removing enzyme.\n\nBut GPX4 is not the only barrier between a cell and ferroptosis. The FSP1–CoQ10 system provides a parallel, glutathione-independent defense by regenerating reduced CoQ, which can trap lipid radicals. Other systems also contribute. Evidence: cell and cancer-model experiments. [8,9]","claim_id":null,"source_key":"deficiency","source_title":"Selenium deficiency: a mechanism-first reference","claim_ids":[]}]}],"research":{"topic":"Selenium scientific audit","plain_language":"Another defense changes how vulnerable cells are to GPX4 loss.","evidence_scope":"direct_experimental","papers":[{"key":"bersuker-2019","title":"The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis","url":"https://www.nature.com/articles/s41586-019-1705-2","doi":"10.1038/s41586-019-1705-2","year":2019,"model":"Cell genetics and biochemical experiments","summary":"FSP1/CoQ provides parallel lipid-radical defense."}]}}