Dixon, S. J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060–1072 (2012).
Madeo, F., Eisenberg, T., Pietrocola, F. & Kroemer, G. Spermidine in health and disease. Science 359, eaan2788 (2018).
Cañeque, T. et al. Activation of lysosomal iron triggers ferroptosis in cancer. Nature 642, 492–500 (2025).
Dai, E. et al. A guideline on the molecular ecosystem regulating ferroptosis. Nat. Cell Biol. 26, 1447–1457 (2024).
Chen, F., Kang, R., Tang, D. & Liu, J. Ferroptosis: principles and significance in health and disease. J. Hematol. Oncol. 17, 41 (2024).
Stockwell, B. R. et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171, 273–285 (2017).
Brown, A. R., Hirschhorn, T. & Stockwell, B. R. Ferroptosis-disease perils and therapeutic promise. Science 386, 848–849 (2024).
Yang, W. S. et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 156, 317–331 (2014).
Doll, S. et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575, 693–698 (2019).
Bersuker, K. et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575, 688–692 (2019).
Li, Y. et al. 7-Dehydrocholesterol dictates ferroptosis sensitivity. Nature 626, 411–418 (2024).
Freitas, F. P. et al. 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis. Nature 626, 401–410 (2024).
Fakler, B. et al. Strong voltage-dependent inward rectification of inward rectifier K+ channels is caused by intracellular spermine. Cell 80, 149–154 (1995).
Ficker, E., Taglialatela, M., Wible, B. A., Henley, C. M. & Brown, A. M. Spermine and spermidine as gating molecules for inward rectifier K+ channels. Science 266, 1068–1072 (1994).
Zabala-Letona, A. et al. Polyamine-dependent metabolic shielding regulates alternative splicing. Nature 651, 819–828 (2026).
Hofer, S. J. et al. Spermidine is essential for fasting-mediated autophagy and longevity. Nat. Cell Biol. 26, 1571–1584 (2024).
Eisenberg, T. et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat. Med. 22, 1428–1438 (2016).
Eisenberg, T. et al. Induction of autophagy by spermidine promotes longevity. Nat. Cell Biol. 11, 1305–1314 (2009).
Kang, R., Liu, J., Wang, J., Kroemer, G. & Tang, D. Translating ferroptosis into oncology: challenges, opportunities and future directions. Nat. Rev. Clin. Oncol. https://doi.org/10.1038/s41571-026-01128-z (2026).
Guri, Y. et al. mTORC2 promotes tumorigenesis via lipid synthesis. Cancer Cell 32, 807–823 (2017).
Dapito, D. H. et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 21, 504–516 (2012).
Li, X. et al. The immunological and metabolic landscape in primary and metastatic liver cancer. Nat. Rev. Cancer 21, 541–557 (2021).
Casero, R. A. Jr., Murray Stewart, T. & Pegg, A. E. Polyamine metabolism and cancer: treatments, challenges and opportunities. Nat. Rev. Cancer 18, 681–695 (2018).
Zabala-Letona, A. et al. mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer. Nature 547, 109–113 (2017).
Bi, G. et al. Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. Nat. Commun. 15, 2461 (2024).
Bae, H. et al. Ferroptosis-activating metabolite acrolein antagonizes necroptosis and anti-cancer therapeutics. Nat. Commun. 16, 4919 (2025).
Sava, I. G., Battaglia, V., Rossi, C. A., Salvi, M. & Toninello, A. Free radical scavenging action of the natural polyamine spermine in rat liver mitochondria. Free Radic. Biol. Med. 41, 1272–1281 (2006).
Mai, T. T. et al. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat. Chem. 9, 1025–1033 (2017).
Lee, M. S. et al. Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer. Nature 616, 339–347 (2023).
Wang, R. et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 35, 871–882 (2011).
Pérez-Arellano, I., Carmona-Alvarez, F., Martínez, A. I., Rodríguez-Díaz, J. & Cervera, J. Pyrroline-5-carboxylate synthase and proline biosynthesis: from osmotolerance to rare metabolic disease. Protein Sci. 19, 372–382 (2010).
Luan, X. et al. Ferroptosis in organ ischemia–reperfusion injuries: recent advancements and strategies. Mol. Cell. Biochem. 480, 19–41 (2025).
Omer, A. K., Mohammed, R. R., Ameen, P. S. M., Abas, Z. A. & Ekici, K. Presence of biogenic amines in food and their public health implications: a review. J. Food Prot. 84, 1539–1548 (2021).
Zhao, Y. J. et al. Role of polyamines in myocardial ischemia/reperfusion injury and their interactions with nitric oxide. Eur. J. Pharmacol. 562, 236–246 (2007).
Hino, K., Yanatori, I., Hara, Y. & Nishina, S. Iron and liver cancer: an inseparable connection. FEBS J. 289, 7810–7829 (2022).
Sun, J. et al. Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring. Nat. Metab. 6, 741–763 (2024).
Yang, M. et al. S100P is a ferroptosis suppressor to facilitate hepatocellular carcinoma development by rewiring lipid metabolism. Nat. Commun. 16, 509 (2025).
Chen, X. et al. A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis. Nat. Commun. 13, 6318 (2022).
Yang, J. S. et al. ALDH7A1 protects against ferroptosis by generating membrane NADH and regulating FSP1. Cell 188, 2569–2585 (2025).
Tang, D., Kroemer, G. & Kang, R. Targeting cuproplasia and cuproptosis in cancer. Nat. Rev. Clin. Oncol. 21, 370–388 (2024).
Sharma, P. et al. Polyamines buffer labile iron to suppress ferroptosis. Preprint at bioRxiv https://doi.org/10.1101/2025.06.30.662349 (2025).
Liu, J. et al. Extracellular GPX4 impairs antitumor immunity via dendritic ZP3 receptors. Cell 189, 1056–1073 (2026).
Jiang, S. et al. Generic Diagramming Platform (GDP): a comprehensive database of high-quality biomedical graphics. Nucleic Acids Res. 53, D1670–D1676 (2025).
Gu, Y. et al. Circular RNA circIPO11 drives self-renewal of liver cancer initiating cells via Hedgehog signaling. Mol. Cancer 20, 132 (2021).
Takami, Y. et al. Systemic aldehyde storm induced by allyl alcohol exposure results in extensive hepatic ferroptosis in Aldh2*2 knock-in mice. Free Radic. Biol. Med. 239, 177–188 (2025).
Domijan, A. M., Ralic, J., Radic Brkanac, S., Rumora, L. & Zanic-Grubisic, T. Quantification of malondialdehyde by HPLC-FL—application to various biological samples. Biomed. Chromatogr. 29, 41–46 (2015).
Shah, R., Farmer, L. A., Zilka, O., Van Kessel, A. T. M. & Pratt, D. A. Beyond DPPH: use of fluorescence-enabled inhibited autoxidation to predict oxidative cell death rescue. Cell Chem. Biol. 26, 1594–1607 (2019).
Poulin, R., Coward, J. K., Lakanen, J. R. & Pegg, A. E. Enhancement of the spermidine uptake system and lethal effects of spermidine overaccumulation in ornithine decarboxylase-overproducing L1210 cells under hyposmotic stress. J. Biol. Chem. 268, 4690–4698 (1993).
Pall, A. E. et al. ATH434, a promising iron-targeting compound for treating iron regulation disorders. Metallomics 16, mfae044 (2024).
Sztula, A., Antal, P., Nemec, I., Kubala, M. & Herchel, R. A novel type of heteroleptic Cu(I) complexes featuring nitrogen-rich tetrazine ligands: syntheses, crystal structures, spectral properties, cyclic voltammetry, and theoretical calculations. Dalton Trans. 54, 5944–5952 (2025).
Li, Z. et al. LPCAT1-mediated membrane phospholipid remodelling promotes ferroptosis evasion and tumour growth. Nat. Cell Biol. 26, 811–824 (2024).
Li, H. et al. YAP/TAZ drives cell proliferation and tumour growth via a polyamine–eIF5A hypusination–LSD1 axis. Nat. Cell Biol. 24, 373–383 (2022).
Horie, Y. et al. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J. Clin. Invest. 113, 1774–1783 (2004).
Fang, X. et al. Malic enzyme 1 as a novel anti-ferroptotic regulator in hepatic ischemia/reperfusion injury. Adv. Sci. 10, e2205436 (2023).
Deng, F. et al. The gut microbiota metabolite capsiate promotes Gpx4 expression by activating TRPV1 to inhibit intestinal ischemia reperfusion-induced ferroptosis. Gut Microbes 13, 1–21 (2021).
Li, X. et al. Small extracellular vesicles delivering lncRNA WAC-AS1 aggravate renal allograft ischemia–reperfusion injury by inducing ferroptosis propagation. Cell Death Differ. 30, 2167–2186 (2023).
Li, R. et al. FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC. Nat. Commun. 15, 4760 (2024).
Zhang, W. et al. Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating Gprc5a signaling. Nat. Commun. 14, 5437 (2023).
Minami, K. et al. Targeting of intragraft reactive oxygen species by APP-103, a novel polymer product, mitigates ischemia/reperfusion injury and promotes the survival of renal transplants. Am. J. Transplant. 20, 1527–1537 (2020).
Vaidya, V. S. et al. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat. Biotechnol. 28, 478–485 (2010).

