Dixon, S. J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060–1072 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yuan, J. & Ofengeim, D. A guide to cell death pathways. Nat. Rev. Mol. Cell Biol. 25, 379–395 (2023).

Article  PubMed  Google Scholar 

Dolma, S., Lessnick, S. L., Hahn, W. C. & Stockwell, B. R. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3, 285–296 (2003).

Article  CAS  PubMed  Google Scholar 

Yang, W. S. & Stockwell, B. R. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem. Biol. 15, 234–245 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Seiler, A. et al. Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab. 8, 237–248 (2008).

Article  CAS  PubMed  Google Scholar 

Doll, S. et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575, 693–698 (2019).

Article  CAS  PubMed  Google Scholar 

Shah, R., Shchepinov, M. S. & Pratt, D. A. Resolving the role of lipoxygenases in the initiation and execution of ferroptosis. ACS Cent. Sci. 4, 387–396 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang, W. S. et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 156, 317–331 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nakamura, T. et al. A tangible method to assess native ferroptosis suppressor activity. Cell Rep. Methods 4, 100710 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xia, C. et al. Cysteine and homocysteine can be exploited by GPX4 in ferroptosis inhibition independent of GSH synthesis. Redox Biol. 69, 102999 (2024).

Article  CAS  PubMed  Google Scholar 

Harris, I. S. et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell 27, 211–222 (2015).

Article  CAS  PubMed  Google Scholar 

Nakamura, T. et al. Phase separation of FSP1 promotes ferroptosis. Nature 619, 371–377 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dixon, S. J. et al. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. eLife 3, e02523 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Barayeu, U. et al. Hydropersulfides inhibit lipid peroxidation and ferroptosis by scavenging radicals. Nat. Chem. Biol. 19, 28–37 (2023).

Article  CAS  PubMed  Google Scholar 

Wu, Z. et al. Hydropersulfides inhibit lipid peroxidation and protect cells from ferroptosis. J. Am. Chem. Soc. 144, 15825–15837 (2022).

Article  CAS  PubMed  Google Scholar 

Zhang, H. F., Klein Geltink, R. I., Parker, S. J. & Sorensen, P. H. Transsulfuration, minor player or crucial for cysteine homeostasis in cancer. Trends Cell Biol. 32, 800–814 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Hayano, M., Yang, W. S., Corn, C. K., Pagano, N. C. & Stockwell, B. R. Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation. Cell Death Differ. 23, 270–278 (2016).

Article  CAS  PubMed  Google Scholar 

Banjac, A. et al. The cystine/cysteine cycle: a redox cycle regulating susceptibility versus resistance to cell death. Oncogene 27, 1618–1628 (2008).

Article  CAS  PubMed  Google Scholar 

Bersuker, K. et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575, 688–692 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mishima, E. et al. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature 608, 778–783 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Deshwal, S. et al. Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7. Nat. Cell Biol. 25, 246–257 (2023).

CAS  PubMed  PubMed Central  Google Scholar 

Kraft, V. A. N. et al. GTP cyclohydrolase 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling. ACS Cent. Sci. 6, 41–53 (2020).

Article  CAS  PubMed  Google Scholar 

Soula, M. et al. Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers. Nat. Chem. Biol. 16, 1351–1360 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Phadnis, V. V. et al. MMD collaborates with ACSL4 and MBOAT7 to promote polyunsaturated phosphatidylinositol remodeling and susceptibility to ferroptosis. Cell Rep. 42, 113023 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Doll, S. et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat. Chem. Biol. 13, 91–98 (2017).

Article  CAS  PubMed  Google Scholar 

Beatty, A. et al. Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1. Nat. Commun. 12, 2244 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang, H. L. et al. PKCβII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis. Nat. Cell Biol. 24, 88–98 (2022).

Article  CAS  PubMed  Google Scholar 

Zou, Y. et al. Plasticity of ether lipids promotes ferroptosis susceptibility and evasion. Nature 585, 603–608 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Reed, A., Ware, T., Li, H., Fernando Bazan, J. & Cravatt, B. F. TMEM164 is an acyltransferase that forms ferroptotic C20:4 ether phospholipids. Nat. Chem. Biol. 19, 378–388 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Magtanong, L. et al. Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state. Cell Chem. Biol. 26, 420–432.e429 (2019).

Article  CAS  PubMed  PubMed Centra