ArticleNature structural & molecular biology2023
Integrated chemical and genetic screens unveil FSP1 mechanisms of ferroptosis regulation.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 67 citations in OpenAlex.
- Disulfidptosis-based cancer therapy: Opportunity and challenge.Genes & diseases · 2027Review
- AI-enhanced adaptive virtual screening of large libraries for ligand discovery.Nature biotechnology · 2026Article
- Review
- Review
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- CoQExperimental & molecular medicine · 2026Review
- Tipping the balance: NRF2's dual role in ferroptotic fate.Oncogenesis · 2026Review
- Metabolic rewiring driven by phosphoglycolate phosphatase deletion inhibits ferroptosis.Science advances · 2026Article
- Cell death pathways and targeting therapeutics in cancer therapy.Acta pharmacologica Sinica · 2026Review
- Metabolic and transcriptional plasticity supports CD8Immunity · 2026Article
- Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.Molecules (Basel, Switzerland) · 2026Review
- Riboflavin metabolism shapes FSP1-driven ferroptosis resistance.Nature cell biology · 2026Article
- AI-Enhanced Adaptive Virtual Screening Platform Enabling Exploration of 69 Billion Molecules Discovers Structurally Validated FSP1 Inhibitors.bioRxiv : the preprint server for biology · 2026Article
- Lipids grease the chain of cancer progression.Trends in cancer · 2026Review
- Vitamin B2 metabolism promotes FSP1 stability to prevent ferroptosis.Nature structural & molecular biology · 2026Article
- A missense mutation in acyl-CoA synthetase ACSL4 reveals essential residues for catalytic activity in ferroptosis.The Journal of biological chemistry · 2026Article
- The Interaction of Structural Analogues of Phenothiazines in p53-Dependent Cellular Signaling Pathways.ACS omega · 2026Article
- Targeting FSP1 triggers ferroptosis in lung cancer.Nature · 2026Article
- Article
- Ferroptosis surveillance: Insights fromFerroptosis and oxidative stress · 2026Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis, marked by iron-dependent lipid peroxidation, may present an Achilles heel for the treatment of cancers. Ferroptosis suppressor protein-1 (FSP1), as the second ferroptosis mainstay, efficiently prevents lipid peroxidation via NAD(P)H-dependent reduction of quinones. Because its molecular mechanisms have remained obscure, we studied numerous FSP1 mutations present in cancer or identified by untargeted random mutagenesis. This mutational analysis elucidates the FAD/NAD(P)H-binding site and proton-transfer function of FSP1, which emerged to be evolutionarily conserved among different NADH quinone reductases. Using random mutagenesis screens, we uncover the mechanism of action of next-generation FSP1 inhibitors. Our studies identify the binding pocket of the first FSP1 inhibitor, iFSP1, and introduce the first species-independent FSP1 inhibitor, targeting the NAD(P)H-binding pocket. Conclusively, our study provides new insights into the molecular functions of FSP1 and enables the rational design of FSP1 inhibitors targeting cancer cells.
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