ArticleNature communications2023
A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 65 citations in OpenAlex.
- MK-4 Ameliorates Post-Ovulatory Aging of Mouse Oocytes by Alleviating Iron Metabolism Disorder-Induced Oxidative Stress.Molecular reproduction and development · 2026Article
- Molecular mechanisms of FSP1-regulated ferroptosis and therapeutic implications in various cancers.Cellular & molecular biology letters · 2026Review
- CoQExperimental & molecular medicine · 2026Review
- Decoding the functional network of circular RNAs encoding proteins in hepatocellular carcinoma: from carcinogenesis to clinical transformation.Journal of advanced research · 2026Review
- The role of estrogen and its receptors in the regulation of ferroptosis and autophagy.Molecular biology reports · 2026Review
- Small-molecule inhibition of γ-glutamyl carboxylase reveals a novel anticoagulant strategy.Blood advances · 2026Article
- The Role of Ferroptosis in Diabetes Pathogenesis: Therapeutic Implications of Hydrogen Sulfide and Its Reactive Metabolites.Antioxidants (Basel, Switzerland) · 2026Review
- Vitamin B2 metabolism promotes FSP1 stability to prevent ferroptosis.Nature structural & molecular biology · 2026Article
- Selective disruption of lipid peroxide homeostasis in intratumoral regulatory T cells by targeting FSP1 enhances cancer immunity.Science advances · 2026Article
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Ferroptosis: a promising therapeutic target for periodontitis.Frontiers in immunology · 2026Review
- The therapeutic potential of vitamins as nutrients in food for anti-inflammatory and anti-oxidative stress in liver fibrosis diseases.Frontiers in nutrition · 2026Review
- Ferroptosis suppressor protein 1-mediated ferroptosis suppression in sepsis: non-canonical antioxidant pathways, inflammatory regulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Loss of ACSL1 fuels ferroptosis resistance in clear cell renal carcinoma.Cancer biology & therapy · 2025Article
- Decoding ferroptosis for cancer therapy.Nature reviews. Cancer · 2025Review
- Review
- Targeting Ferroptosis in Nasopharyngeal Carcinoma: Mechanisms, Resistance, and Precision Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- FSP1-mediated lipid droplet quality control prevents neutral lipid peroxidation and ferroptosis.Nature cell biology · 2025Article
- Cocrystal structure reveals the mechanism of FSP1 inhibition by FSEN1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Chinese patient with cardiogenic stroke and warfarin resistance: a case report.BMC neurology · 2025Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Vitamin K is a vital micronutrient implicated in a variety of human diseases. Warfarin, a vitamin K antagonist, is the most commonly prescribed oral anticoagulant. Patients overdosed on warfarin can be rescued by administering high doses of vitamin K because of the existence of a warfarin-resistant vitamin K reductase. Despite the functional discovery of vitamin K reductase over eight decades ago, its identity remained elusive. Here, we report the identification of warfarin-resistant vitamin K reductase using a genome-wide CRISPR-Cas9 knockout screen with a vitamin K-dependent apoptotic reporter cell line. We find that ferroptosis suppressor protein 1 (FSP1), a ubiquinone oxidoreductase, is the enzyme responsible for vitamin K reduction in a warfarin-resistant manner, consistent with a recent discovery by Mishima et al. FSP1 inhibitor that inhibited ubiquinone reduction and thus triggered cancer cell ferroptosis, displays strong inhibition of vitamin K-dependent carboxylation. Intriguingly, dihydroorotate dehydrogenase, another ubiquinone-associated ferroptosis suppressor protein parallel to the function of FSP1, does not support vitamin K-dependent carboxylation. These findings provide new insights into selectively controlling the physiological and pathological processes involving electron transfers mediated by vitamin K and ubiquinone.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.