Zooming in and out of ferroptosis in human disease

Abstract

Ferroptosis is defined as an iron-dependent regulated form of cell death driven by lipid peroxidation. In the past decade, it has been implicated in the pathogenesis of various diseases that together involve almost every organ of the body, including various cancers, neurodegenerative diseases, cardiovascular diseases, lung diseases, liver diseases, kidney diseases, endocrine metabolic diseases, iron-overload-related diseases, orthopedic diseases and autoimmune diseases. Understanding the underlying molecular mechanisms of ferroptosis and its regulatory pathways could provide additional strategies for the management of these disease conditions. Indeed, there are an expanding number of studies suggesting that ferroptosis serves as a bona-fide target for the prevention and treatment of these diseases in relevant pre-clinical models. In this review, we summarize the progress in the research into ferroptosis and its regulatory mechanisms in human disease, while providing evidence in support of ferroptosis as a target for the treatment of these diseases. We also discuss our perspectives on the future directions in the targeting of ferroptosis in human disease.

Keywords

ferroptosis / human disease / iron metabolism / lipid peroxidation / antioxidation

References

[1] Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol 2021; 22(4): 266–282

[2] Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 2012; 149(5): 1060–1072

[3] Green DR. The coming decade of cell death research: five riddles. Cell 2019; 177(5): 1094–1107

[4] Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, Herbach N, Aichler M, Walch A, Eggenhofer E, Basavarajappa D, Rådmark O, Kobayashi S, Seibt T, Beck H, Neff F, Esposito I, Wanke R, Förster H, Yefremova O, Heinrichmeyer M, Bornkamm GW, Geissler EK, Thomas SB, Stockwell BR, O’Donnell VB, Kagan VE, Schick JA, Conrad M. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol 2014; 16(12): 1180–1191

[5] Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X, Kang R, Tang D. Ferroptosis: process and function. Cell Death Differ 2016; 23(3): 369–379

[6] Kim SE, Zhang L, Ma K, Riegman M, Chen F, Ingold I, Conrad M, Turker MZ, Gao M, Jiang X, Monette S, Pauliah M, Gonen M, Zanzonico P, Quinn T, Wiesner U, Bradbury MS, Overholtzer M. Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth. Nat Nanotechnol 2016; 11(11): 977–985

[7] Kagan VE, Mao G, Qu F, Angeli JP, Doll S, Croix CS, Dar HH, Liu B, Tyurin VA, Ritov VB, Kapralov AA, Amoscato AA, Jiang J, Anthonymuthu T, Mohammadyani D, Yang Q, Proneth B, Klein-Seetharaman J, Watkins S, Bahar I, Greenberger J, Mallampalli RK, Stockwell BR, Tyurina YY, Conrad M, Bayır H. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol 2017; 13(1): 81–90

[8] Magtanong L, Ko PJ, To M, Cao JY, Forcina GC, Tarangelo A, Ward CC, Cho K, Patti GJ, Nomura DK, Olzmann JA, Dixon SJ. Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state. Cell Chem Biol 2019; 26(3): 420–432.e9

[9] Zou Y, Henry WS, Ricq EL, Graham ET, Phadnis VV, Maretich P, Paradkar S, Boehnke N, Deik AA, Reinhardt F, Eaton JK, Ferguson B, Wang W, Fairman J, Keys HR, Dančík V, Clish CB, Clemons PA, Hammond PT, Boyer LA, Weinberg RA, Schreiber SL. Plasticity of ether lipids promotes ferroptosis susceptibility and evasion. Nature 2020; 585(7826): 603–608

[10] Perez MA, Magtanong L, Dixon SJ, Watts JL. Dietary lipids induce ferroptosis in Caenorhabditis elegans and human cancer cells. Dev Cell 2020; 54(4): 447–454.e4

[11] Cui W, Liu D, Gu W, Chu B. Peroxisome-driven ether-linked phospholipids biosynthesis is essential for ferroptosis. Cell Death Differ 2021; 28(8): 2536–2551

[12] Liu Y, He L, Liu B, Ying Y, Xu J, Yu M, Dang J, Liu K. Pharmacological inhibition of sphingolipid synthesis reduces ferroptosis by stimulating the HIF-1 pathway. iScience 2022; 25(7): 104533

[13] Thayyullathil F, Cheratta AR, Alakkal A, Subburayan K, Pallichankandy S, Hannun YA, Galadari S. Acid sphingomyelinase-dependent autophagic degradation of GPX4 is critical for the execution of ferroptosis. Cell Death Dis 2021; 12(1): 26

[14] Thomas JP, Geiger PG, Maiorino M, Ursini F, Girotti AW. Enzymatic reduction of phospholipid and cholesterol hydroperoxides in artificial bilayers and lipoproteins. Biochim Biophys Acta 1990; 1045(3): 252–260

[15] Garcia-Bermudez J, Baudrier L, Bayraktar EC, Shen Y, La K, Guarecuco R, Yucel B, Fiore D, Tavora B, Freinkman E, Chan SH, Lewis C, Min W, Inghirami G, Sabatini DM, Birsoy K. Squalene accumulation in cholesterol auxotrophic lymphomas prevents oxidative cell death. Nature 2019; 567(7746): 118–122

[16] Ma X, Xiao L, Liu L, Ye L, Su P, Bi E, Wang Q, Yang M, Qian J, Yi Q. CD36-mediated ferroptosis dampens intratumoral CD8⁺ T cell effector function and impairs their antitumor ability. Cell Metab 2021; 33(5): 1001–1012.e5

[17] Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, Irmler M, Beckers J, Aichler M, Walch A, Prokisch H, Trümbach D, Mao G, Qu F, Bayir H, Füllekrug J, Scheel CH, Wurst W, Schick JA, Kagan VE, Angeli JP, Conrad M. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol 2017; 13(1): 91–98

[18] Zhang HL, Hu BX, Li ZL, Du T, Shan JL, Ye ZP, Peng XD, Li X, Huang Y, Zhu XY, Chen YH, Feng GK, Yang D, Deng R, Zhu XF. PKCβII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis. Nat Cell Biol 2022; 24(1): 88–98

[19] Wu J, Minikes AM, Gao M, Bian H, Li Y, Stockwell BR, Chen ZN, Jiang X. Intercellular interaction dictates cancer cell ferroptosis via NF2-YAP signalling. Nature 2019; 572(7769): 402–406

[20] Beatty A, Singh T, Tyurina YY, Tyurin VA, Samovich S, Nicolas E, Maslar K, Zhou Y, Cai KQ, Tan Y, Doll S, Conrad M, Subramanian A, Bayır H, Kagan VE, Rennefahrt U, Peterson JR. Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1. Nat Commun 2021; 12(1): 2244

[21] Hashidate-Yoshida T, Harayama T, Hishikawa D, Morimoto R, Hamano F, Tokuoka SM, Eto M, Tamura-Nakano M, Yanobu-Takanashi R, Mukumoto Y, Kiyonari H, Okamura T, Kita Y, Shindou H, Shimizu T. Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport. Elife 2015; 4: e06328

[22] Venkatesh D, O’Brien NA, Zandkarimi F, Tong DR, Stokes ME, Dunn DE, Kengmana ES, Aron AT, Klein AM, Csuka JM, Moon SH, Conrad M, Chang CJ, Lo DC, D’Alessandro A, Prives C, Stockwell BR. MDM2 and MDMX promote ferroptosis by PPARα-mediated lipid remodeling. Genes Dev 2020; 34(7–8): 526–543

[23] Kaller M, Liffers ST, Oeljeklaus S, Kuhlmann K, Röh S, Hoffmann R, Warscheid B, Hermeking H. Genome-wide characterization of miR-34a induced changes in protein and mRNA expression by a combined pulsed SILAC and microarray analysis. Mol Cell Proteomics 2011; 10(8): M111.010462

[24] Bai C, Gao Y, Zhang X, Yang W, Guan W. MicroRNA-34c acts as a bidirectional switch in the maturation of insulin-producing cells derived from mesenchymal stem cells. Oncotarget 2017; 8(63): 106844–106857

[25] Dong LH, Huang JJ, Zu P, Liu J, Gao X, Du JW, Li YF. CircKDM4C upregulates P53 by sponging hsa-let-7b-5p to induce ferroptosis in acute myeloid leukemia. Environ Toxicol 2021; 36(7): 1288–1302

[26] Ye S, Xu M, Zhu T, Chen J, Shi S, Jiang H, Zheng Q, Liao Q, Ding X, Xi Y. Cytoglobin promotes sensitivity to ferroptosis by regulating p53-YAP1 axis in colon cancer cells. J Cell Mol Med 2021; 25(7): 3300–3311

[27] Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H, Baer R, Gu W. Ferroptosis as a p53-mediated activity during tumour suppression. Nature 2015; 520(7545): 57–62

[28] Chen D, Chu B, Yang X, Liu Z, Jin Y, Kon N, Rabadan R, Jiang X, Stockwell BR, Gu W. iPLA2β-mediated lipid detoxification controls p53-driven ferroptosis independent of GPX4. Nat Commun 2021; 12(1): 3644

[29] Lee H, Zandkarimi F, Zhang Y, Meena JK, Kim J, Zhuang L, Tyagi S, Ma L, Westbrook TF, Steinberg GR, Nakada D, Stockwell BR, Gan B. Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat Cell Biol 2020; 22(2): 225–234

[30] Gaschler MM, Hu F, Feng H, Linkermann A, Min W, Stockwell BR. Determination of the subcellular localization and mechanism of action of ferrostatins in suppressing ferroptosis. ACS Chem Biol 2018; 13(4): 1013–1020

[31] Hao L, Zhong YM, Tan CP, Mao ZW. Quantitative tracking of endoplasmic reticulum viscosity during ferroptosis by an iridium complex via TPPLM. Chem Commun (Camb) 2021; 57(41): 5040–5042

[32] Agmon E, Solon J, Bassereau P, Stockwell BR. Modeling the effects of lipid peroxidation during ferroptosis on membrane properties. Sci Rep 2018; 8(1): 5155

[33] Pedrera L, Espiritu RA, Ros U, Weber J, Schmitt A, Stroh J, Hailfinger S, von Karstedt S, García-Sáez AJ. Ferroptotic pores induce Ca²⁺ fluxes and ESCRT-III activation to modulate cell death kinetics. Cell Death Differ 2021; 28(5): 1644–1657

[34] Bannai S. Exchange of cystine and glutamate across plasma membrane of human fibroblasts. J Biol Chem 1986; 261(5): 2256–2263

[35] Wang L, Liu Y, Du T, Yang H, Lei L, Guo M, Ding HF, Zhang J, Wang H, Chen X, Yan C. ATF3 promotes erastin-induced ferroptosis by suppressing system Xc^–. Cell Death Differ 2020; 27(2): 662–675

[36] Rojo de la Vega M, Chapman E, Zhang DD. NRF2 and the hallmarks of cancer. Cancer Cell 2018; 34(1): 21–43

[37] Fan Z, Wirth AK, Chen D, Wruck CJ, Rauh M, Buchfelder M, Savaskan N. Nrf2-Keap1 pathway promotes cell proliferation and diminishes ferroptosis. Oncogenesis 2017; 6(8): e371

[38] Cao JY, Poddar A, Magtanong L, Lumb JH, Mileur TR, Reid MA, Dovey CM, Wang J, Locasale JW, Stone E, Cole SPC, Carette JE, Dixon SJ. A genome-wide haploid genetic screen identifies regulators of glutathione abundance and ferroptosis sensitivity. Cell Rep 2019; 26(6): 1544–1556.e8

[39] Hao S, Yu J, He W, Huang Q, Zhao Y, Liang B, Zhang S, Wen Z, Dong S, Rao J, Liao W, Shi M. Cysteine dioxygenase 1 mediates erastin-induced ferroptosis in human gastric cancer cells. Neoplasia 2017; 19(12): 1022–1032

[40] Kang YP, Mockabee-Macias A, Jiang C, Falzone A, Prieto-Farigua N, Stone E, Harris IS, DeNicola GM. Non-canonical glutamate-cysteine ligase activity protects against ferroptosis. Cell Metab 2021; 33(1): 174–189.e7

[41] FangXZhang JLiYSongYYuY CaiZLianF YangJMin JWangF. Malic enzyme 1 as a novel anti-ferroptotic regulator in hepatic ischemia/reperfusion injury. Adv Sci (Weinh) 2023; [Epub ahead of print]

[42] Shimada K, Skouta R, Kaplan A, Yang WS, Hayano M, Dixon SJ, Brown LM, Valenzuela CA, Wolpaw AJ, Stockwell BR. Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat Chem Biol 2016; 12(7): 497–503

[43] Wu Z, Geng Y, Lu X, Shi Y, Wu G, Zhang M, Shan B, Pan H, Yuan J. Chaperone-mediated autophagy is involved in the execution of ferroptosis. Proc Natl Acad Sci U S A 2019; 116(8): 2996–3005

[44] Mishima E, Ito J, Wu Z, Nakamura T, Wahida A, Doll S, Tonnus W, Nepachalovich P, Eggenhofer E, Aldrovandi M, Henkelmann B, Yamada KI, Wanninger J, Zilka O, Sato E, Feederle R, Hass D, Maida A, Mourão ASD, Linkermann A, Geissler EK, Nakagawa K, Abe T, Fedorova M, Proneth B, Pratt DA, Conrad M. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature 2022; 608(7924): 778–783

[45] Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, Roberts MA, Tong B, Maimone TJ, Zoncu R, Bassik MC, Nomura DK, Dixon SJ, Olzmann JA. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 2019; 575(7784): 688–692

[46] Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, Goya Grocin A, Xavier da Silva TN, Panzilius E, Scheel CH, Mourão A, Buday K, Sato M, Wanninger J, Vignane T, Mohana V, Rehberg M, Flatley A, Schepers A, Kurz A, White D, Sauer M, Sattler M, Tate EW, Schmitz W, Schulze A, O’Donnell V, Proneth B, Popowicz GM, Pratt DA, Angeli JPF, Conrad M. FSP1 is a glutathione-independent ferroptosis suppressor. Nature 2019; 575(7784): 693–698

[47] Mao C, Liu X, Zhang Y, Lei G, Yan Y, Lee H, Koppula P, Wu S, Zhuang L, Fang B, Poyurovsky MV, Olszewski K, Gan B. DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. Nature 2021; 593(7860): 586–590

[48] Werner ER, Blau N, Thöny B. Tetrahydrobiopterin: biochemistry and pathophysiology. Biochem J 2011; 438(3): 397–414

[49] Kraft VAN, Bezjian CT, Pfeiffer S, Ringelstetter L, Müller C, Zandkarimi F, Merl-Pham J, Bao X, Anastasov N, Kössl J, Brandner S, Daniels JD, Schmitt-Kopplin P, Hauck SM, Stockwell BR, Hadian K, Schick JA. GTP cyclohydrolase 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling. ACS Cent Sci 2020; 6(1): 41–53

[50] Soula M, Weber RA, Zilka O, Alwaseem H, La K, Yen F, Molina H, Garcia-Bermudez J, Pratt DA, Birsoy K. Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers. Nat Chem Biol 2020; 16(12): 1351–1360

[51] Zeitler L, Fiore A, Meyer C, Russier M, Zanella G, Suppmann S, Gargaro M, Sidhu SS, Seshagiri S, Ohnmacht C, Köcher T, Fallarino F, Linkermann A, Murray PJ. Anti-ferroptotic mechanism of IL4i1-mediated amino acid metabolism. Elife 2021; 10: e64806

[52] Yu Y, Jiang L, Wang H, Shen Z, Cheng Q, Zhang P, Wang J, Wu Q, Fang X, Duan L, Wang S, Wang K, An P, Shao T, Chung RT, Zheng S, Min J, Wang F. Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis. Blood 2020; 136(6): 726–739

[53] Muckenthaler MU, Rivella S, Hentze MW, Galy B. A red carpet for iron metabolism. Cell 2017; 168(3): 344–361

[54] Zhang F, Tao Y, Zhang Z, Guo X, An P, Shen Y, Wu Q, Yu Y, Wang F. Metalloreductase Steap3 coordinates the regulation of iron homeostasis and inflammatory responses. Haematologica 2012; 97(12): 1826–1835

[55] Protchenko O, Baratz E, Jadhav S, Li F, Shakoury-Elizeh M, Gavrilova O, Ghosh MC, Cox JE, Maschek JA, Tyurin VA, Tyurina YY, Bayir H, Aron AT, Chang CJ, Kagan VE, Philpott CC. Iron chaperone poly rC binding protein 1 protects mouse liver from lipid peroxidation and steatosis. Hepatology 2021; 73(3): 1176–1193

[56] Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab 2005; 1(3): 191–200

[57] Jiang L, Wang J, Wang K, Wang H, Wu Q, Yang C, Yu Y, Ni P, Zhong Y, Song Z, Xie E, Hu R, Min J, Wang F. RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity by modulating ferroportin degradation. Blood 2021; 138(8): 689–705

[58] Zhang Z, Zhang F, An P, Guo X, Shen Y, Tao Y, Wu Q, Zhang Y, Yu Y, Ning B, Nie G, Knutson MD, Anderson GJ, Wang F. Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses. Blood 2011; 118(7): 1912–1922

[59] Tian R, Abarientos A, Hong J, Hashemi SH, Yan R, Dräger N, Leng K, Nalls MA, Singleton AB, Xu K, Faghri F, Kampmann M. Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis. Nat Neurosci 2021; 24(7): 1020–1034

[60] Feng H, Schorpp K, Jin J, Yozwiak CE, Hoffstrom BG, Decker AM, Rajbhandari P, Stokes ME, Bender HG, Csuka JM, Upadhyayula PS, Canoll P, Uchida K, Soni RK, Hadian K, Stockwell BR. Transferrin receptor is a specific ferroptosis marker. Cell Rep 2020; 30(10): 3411–3423.e7

[61] Paradkar PN, Zumbrennen KB, Paw BH, Ward DM, Kaplan J. Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2. Mol Cell Biol 2009; 29(4): 1007–1016

[62] Shaw GC, Cope JJ, Li L, Corson K, Hersey C, Ackermann GE, Gwynn B, Lambert AJ, Wingert RA, Traver D, Trede NS, Barut BA, Zhou Y, Minet E, Donovan A, Brownlie A, Balzan R, Weiss MJ, Peters LL, Kaplan J, Zon LI, Paw BH. Mitoferrin is essential for erythroid iron assimilation. Nature 2006; 440(7080): 96–100

[63] Zhang Z, Guo M, Shen M, Kong D, Zhang F, Shao J, Tan S, Wang S, Chen A, Cao P, Zheng S. The BRD7-P53-SLC25A28 axis regulates ferroptosis in hepatic stellate cells. Redox Biol 2020; 36: 101619

[64] Kwon MY, Park E, Lee SJ, Chung SW. Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death. Oncotarget 2015; 6(27): 24393–24403

[65] Chang LC, Chiang SK, Chen SE, Yu YL, Chou RH, Chang WC. Heme oxygenase-1 mediates BAY 11-7085 induced ferroptosis. Cancer Lett 2018; 416: 124–137

[66] Fang X, Wang H, Han D, Xie E, Yang X, Wei J, Gu S, Gao F, Zhu N, Yin X, Cheng Q, Zhang P, Dai W, Chen J, Yang F, Yang HT, Linkermann A, Gu W, Min J, Wang F. Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci U S A 2019; 116(7): 2672–2680

[67] Adedoyin O, Boddu R, Traylor A, Lever JM, Bolisetty S, George JF, Agarwal A. Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells. Am J Physiol Renal Physiol 2018; 314(5): F702–F714

[68] Wang YQ, Chang SY, Wu Q, Gou YJ, Jia L, Cui YM, Yu P, Shi ZH, Wu WS, Gao G, Chang YZ. The protective role of mitochondrial ferritin on erastin-induced ferroptosis. Front Aging Neurosci 2016; 8: 308

[69] Alvarez SW, Sviderskiy VO, Terzi EM, Papagiannakopoulos T, Moreira AL, Adams S, Sabatini DM, Birsoy K, Possemato R. NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature 2017; 551(7682): 639–643

[70] Yuan H, Li X, Zhang X, Kang R, Tang D. CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation. Biochem Biophys Res Commun 2016; 478(2): 838–844

[71] Kim EH, Shin D, Lee J, Jung AR, Roh JL. CISD2 inhibition overcomes resistance to sulfasalazine-induced ferroptotic cell death in head and neck cancer. Cancer Lett 2018; 432: 180–190

[72] Shah R, Shchepinov MS, Pratt DA. Resolving the role of lipoxygenases in the initiation and execution of ferroptosis. ACS Cent Sci 2018; 4(3): 387–396

[73] Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci U S A 2016; 113(34): E4966–E4975

[74] Wenzel SE, Tyurina YY, Zhao J, St Croix CM, Dar HH, Mao G, Tyurin VA, Anthonymuthu TS, Kapralov AA, Amoscato AA, Mikulska-Ruminska K, Shrivastava IH, Kenny EM, Yang Q, Rosenbaum JC, Sparvero LJ, Emlet DR, Wen X, Minami Y, Qu F, Watkins SC, Holman TR, VanDemark AP, Kellum JA, Bahar I, Bayır H, Kagan VE. PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell 2017; 171(3): 628–641.e26

[75] Chu B, Kon N, Chen D, Li T, Liu T, Jiang L, Song S, Tavana O, Gu W. ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway. Nat Cell Biol 2019; 21(5): 579–591

[76] Zou Y, Li H, Graham ET, Deik AA, Eaton JK, Wang W, Sandoval-Gomez G, Clish CB, Doench JG, Schreiber SL. Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis. Nat Chem Biol 2020; 16(3): 302–309

[77] Lei G, Zhuang L, Gan B. Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer 2022; 22(7): 381–396

[78] Tan SK, Mahmud I, Fontanesi F, Puchowicz M, Neumann CKA, Griswold AJ, Patel R, Dispagna M, Ahmed HH, Gonzalgo ML, Brown JM, Garrett TJ, Welford SM. Obesity-dependent adipokine chemerin suppresses fatty acid oxidation to confer ferroptosis resistance. Cancer Discov 2021; 11(8): 2072–2093

[79] Sun WY, Tyurin VA, Mikulska-Ruminska K, Shrivastava IH, Anthonymuthu TS, Zhai YJ, Pan MH, Gong HB, Lu DH, Sun J, Duan WJ, Korolev S, Abramov AY, Angelova PR, Miller I, Beharier O, Mao GW, Dar HH, Kapralov AA, Amoscato AA, Hastings TG, Greenamyre TJ, Chu CT, Sadovsky Y, Bahar I, Bayır H, Tyurina YY, He RR, Kagan VE. Phospholipase iPLA₂β averts ferroptosis by eliminating a redox lipid death signal. Nat Chem Biol 2021; 17(4): 465–476

[80] Liu W, Chakraborty B, Safi R, Kazmin D, Chang CY, McDonnell DP. Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer. Nat Commun 2021; 12(1): 5103

[81] Koppula P, Zhang Y, Zhuang L, Gan B. Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer. Cancer Commun (Lond) 2018; 38(1): 12

[82] Koppula P, Zhuang L, Gan B. Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy. Protein Cell 2021; 12(8): 599–620

[83] Dodson M, Castro-Portuguez R, Zhang DD. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol 2019; 23: 101107

[84] Anandhan A, Dodson M, Schmidlin CJ, Liu P, Zhang DD. Breakdown of an ironclad defense system: the critical role of NRF2 in mediating ferroptosis. Cell Chem Biol 2020; 27(4): 436–447

[85] Zhang Y, Shi J, Liu X, Feng L, Gong Z, Koppula P, Sirohi K, Li X, Wei Y, Lee H, Zhuang L, Chen G, Xiao ZD, Hung MC, Chen J, Huang P, Li W, Gan B. BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat Cell Biol 2018; 20(10): 1181–1192

[86] Hu K, Li K, Lv J, Feng J, Chen J, Wu H, Cheng F, Jiang W, Wang J, Pei H, Chiao PJ, Cai Z, Chen Y, Liu M, Pang X. Suppression of the SLC7A11/glutathione axis causes synthetic lethality in KRAS-mutant lung adenocarcinoma. J Clin Invest 2020; 130(4): 1752–1766

[87] Lim JKM, Delaidelli A, Minaker SW, Zhang HF, Colovic M, Yang H, Negri GL, von Karstedt S, Lockwood WW, Schaffer P, Leprivier G, Sorensen PH. Cystine/glutamate antiporter xCT (SLC7A11) facilitates oncogenic RAS transformation by preserving intracellular redox balance. Proc Natl Acad Sci U S A 2019; 116(19): 9433–9442

[88] Manz DH, Blanchette NL, Paul BT, Torti FM, Torti SV. Iron and cancer: recent insights. Ann N Y Acad Sci 2016; 1368(1): 149–161

[89] Du J, Zhou Y, Li Y, Xia J, Chen Y, Chen S, Wang X, Sun W, Wang T, Ren X, Wang X, An Y, Lu K, Hu W, Huang S, Li J, Tong X, Wang Y. Identification of frataxin as a regulator of ferroptosis. Redox Biol 2020; 32: 101483

[90] Zhang C, Liu X, Jin S, Chen Y, Guo R. Ferroptosis in cancer therapy: a novel approach to reversing drug resistance. Mol Cancer 2022; 21(1): 47

[91] Tang X, Ding H, Liang M, Chen X, Yan Y, Wan N, Chen Q, Zhang J, Cao J. Curcumin induces ferroptosis in non-small-cell lung cancer via activating autophagy. Thorac Cancer 2021; 12(8): 1219–1230

[92] Tian X, Li S, Ge G. Apatinib promotes ferroptosis in colorectal cancer cells by targeting ELOVL6/ACSL4 signaling. Cancer Manag Res 2021; 13: 1333–1342

[93] Ndiaye H, Liu JY, Hall A, Minogue S, Morgan MY, Waugh MG. Immunohistochemical staining reveals differential expression of ACSL3 and ACSL4 in hepatocellular carcinoma and hepatic gastrointestinal metastases. Biosci Rep 2020; 40(4): BSR20200219

[94] Yuan H, Li X, Zhang X, Kang R, Tang D. Identification of ACSL4 as a biomarker and contributor of ferroptosis. Biochem Biophys Res Commun 2016; 478(3): 1338–1343

[95] Ye Z, Hu Q, Zhuo Q, Zhu Y, Fan G, Liu M, Sun Q, Zhang Z, Liu W, Xu W, Ji S, Yu X, Xu X, Qin Y. Abrogation of ARF6 promotes RSL3-induced ferroptosis and mitigates gemcitabine resistance in pancreatic cancer cells. Am J Cancer Res 2020; 10(4): 1182–1193

[96] Zhang H, Deng T, Liu R, Ning T, Yang H, Liu D, Zhang Q, Lin D, Ge S, Bai M, Wang X, Zhang L, Li H, Yang Y, Ji Z, Wang H, Ying G, Ba Y. CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer 2020; 19(1): 43

[97] Kuang F, Liu J, Xie Y, Tang D, Kang R. MGST1 is a redox-sensitive repressor of ferroptosis in pancreatic cancer cells. Cell Chem Biol 2021; 28(6): 765–775.e5

[98] Zhou W, Zhang J, Yan M, Wu J, Lian S, Sun K, Li B, Ma J, Xia J, Lian C. Orlistat induces ferroptosis-like cell death of lung cancer cells. Front Med 2021; 15(6): 922–932

[99] Yang C, Zhang Y, Lin S, Liu Y, Li W. Suppressing the KIF20A/NUAK1/Nrf2/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin. Aging (Albany NY) 2021; 13(10): 13515–13534

[100] Huang W, Chen K, Lu Y, Zhang D, Cheng Y, Li L, Huang W, He G, Liao H, Cai L, Tang Y, Zhao L, Pan M. ABCC5 facilitates the acquired resistance of sorafenib through the inhibition of SLC7A11-induced ferroptosis in hepatocellular carcinoma. Neoplasia 2021; 23(12): 1227–1239

[101] Fu D, Wang C, Yu L, Yu R. Induction of ferroptosis by ATF3 elevation alleviates cisplatin resistance in gastric cancer by restraining Nrf2/Keap1/xCT signaling. Cell Mol Biol Lett 2021; 26(1): 26

[102] Cai S, Fu S, Zhang W, Yuan X, Cheng Y, Fang J. SIRT6 silencing overcomes resistance to sorafenib by promoting ferroptosis in gastric cancer. Biochem Biophys Res Commun 2021; 577: 158–164

[103] FengCZLi NZHuXBXieYYHuangQH ZhangJChen ZChenSJWangFSunXJ. The LIFR-targeting small molecules EC330/EC359 are potent ferroptosis inducers. Genes Dis 2022; [Epub ahead of print] doi:10.1016/j.gendis.2022.10.016

[104] Wang K, Zhang Z, Tsai HI, Liu Y, Gao J, Wang M, Song L, Cao X, Xu Z, Chen H, Gong A, Wang D, Cheng F, Zhu H. Branched-chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells. Cell Death Differ 2021; 28(4): 1222–1236

[105] Chaudhary N, Choudhary BS, Shah SG, Khapare N, Dwivedi N, Gaikwad A, Joshi N, Raichanna J, Basu S, Gurjar M, P K S, Saklani A, Gera P, Ramadwar M, Patil P, Thorat R, Gota V, Dhar SK, Gupta S, Das M, Dalal SN. Lipocalin 2 expression promotes tumor progression and therapy resistance by inhibiting ferroptosis in colorectal cancer. Int J Cancer 2021; 149(7): 1495–1511

[106] Shang Y, Luo M, Yao F, Wang S, Yuan Z, Yang Y. Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. Cell Signal 2020; 72: 109633

[107] Bai T, Wang S, Zhao Y, Zhu R, Wang W, Sun Y. Haloperidol, a sigma receptor 1 antagonist, promotes ferroptosis in hepatocellular carcinoma cells. Biochem Biophys Res Commun 2017; 491(4): 919–925

[108] Turcu AL, Versini A, Khene N, Gaillet C, Cañeque T, Müller S, Rodriguez R. DMT1 inhibitors kill cancer stem cells by blocking lysosomal iron translocation. Chemistry 2020; 26(33): 7369–7373

[109] Cao X, Li Y, Wang Y, Yu T, Zhu C, Zhang X, Guan J. Curcumin suppresses tumorigenesis by ferroptosis in breast cancer. PLoS One 2022; 17(1): e0261370

[110] Du J, Wang X, Li Y, Ren X, Zhou Y, Hu W, Zhou C, Jing Q, Yang C, Wang L, Li H, Fang L, Zhou Y, Tong X, Wang Y. DHA exhibits synergistic therapeutic efficacy with cisplatin to induce ferroptosis in pancreatic ductal adenocarcinoma via modulation of iron metabolism. Cell Death Dis 2021; 12(7): 705

[111] Song Z, Xiang X, Li J, Deng J, Fang Z, Zhang L, Xiong J. Ruscogenin induces ferroptosis in pancreatic cancer cells. Oncol Rep 2020; 43(2): 516–524

[112] Wang HT, Ju J, Wang SC, Zhang YH, Liu CY, Wang T, Yu X, Wang F, Cheng XR, Wang K, Chen ZY. Insights into ferroptosis, a novel target for the therapy of cancer. Front Oncol 2022; 12: 812534

[113] Lei G, Mao C, Yan Y, Zhuang L, Gan B. Ferroptosis, radiotherapy, and combination therapeutic strategies. Protein Cell 2021; 12(11): 836–857

[114] Xu S, Min J, Wang F. Ferroptosis: an emerging player in immune cells. Sci Bull (Beijing) 2021; 66(22): 2257–2260

[115] Mu Q, Chen L, Gao X, Shen S, Sheng W, Min J, Wang F. The role of iron homeostasis in remodeling immune function and regulating inflammatory disease. Sci Bull (Beijing) 2021; 66(17): 1806–1816

[116] Hambright WS, Fonseca RS, Chen L, Na R, Ran Q. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox Biol 2017; 12: 8–17

[117] Park MW, Cha HW, Kim J, Kim JH, Yang H, Yoon S, Boonpraman N, Yi SS, Yoo ID, Moon JS. NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer’s diseases. Redox Biol 2021; 41: 101947

[118] Huang L, McClatchy DB, Maher P, Liang Z, Diedrich JK, Soriano-Castell D, Goldberg J, Shokhirev M, Yates JR 3rd, Schubert D, Currais A. Intracellular amyloid toxicity induces oxytosis/ferroptosis regulated cell death. Cell Death Dis 2020; 11(10): 828

[119] Ayton S, Portbury S, Kalinowski P, Agarwal P, Diouf I, Schneider JA, Morris MC, Bush AI. Regional brain iron associated with deterioration in Alzheimer’s disease: a large cohort study and theoretical significance. Alzheimers Dement 2021; 17(7): 1244–1256

[120] Bao WD, Pang P, Zhou XT, Hu F, Xiong W, Chen K, Wang J, Wang F, Xie D, Hu YZ, Han ZT, Zhang HH, Wang WX, Nelson PT, Chen JG, Lu Y, Man HY, Liu D, Zhu LQ. Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease. Cell Death Differ 2021; 28(5): 1548–1562

[121] Zhu ZY, Liu YD, Gong Y, Jin W, Topchiy E, Turdi S, Gao YF, Culver B, Wang SY, Ge W, Zha WL, Ren J, Pei ZH, Qin X. Mitochondrial aldehyde dehydrogenase (ALDH2) rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer’s disease via inhibition of ACSL4-dependent ferroptosis. Acta Pharmacol Sin 2022; 43(1): 39–49

[122] Gao Y, Li J, Wu Q, Wang S, Yang S, Li X, Chen N, Li L, Zhang L. Tetrahydroxy stilbene glycoside ameliorates Alzheimer’s disease in APP/PS1 mice via glutathione peroxidase related ferroptosis. Int Immunopharmacol 2021; 99: 108002

[123] Wang C, Chen S, Guo H, Jiang H, Liu H, Fu H, Wang D. Forsythoside A mitigates Alzheimer’s-like pathology by inhibiting ferroptosis-mediated neuroinflammation via Nrf2/GPX4 axis activation. Int J Biol Sci 2022; 18(5): 2075–2090

[124] Li L, Li WJ, Zheng XR, Liu QL, Du Q, Lai YJ, Liu SQ. Eriodictyol ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via vitamin D receptor-mediated Nrf2 activation. Mol Med 2022; 28(1): 11

[125] BelaidiAAMasaldan SSouthonAKalinowskiPAcevedoK AppukuttanATPortburySLeiP AgarwalPLeurgans SESchneiderJConradMBushAI AytonS. Apolipoprotein E potently inhibits ferroptosis by blocking ferritinophagy. Mol Psychiatry 2022; [Epub ahead of print] doi:10.1038/s41380-022-01568-w

[126] Zhang YH, Wang DW, Xu SF, Zhang S, Fan YG, Yang YY, Guo SQ, Wang S, Guo T, Wang ZY, Guo C. α-Lipoic acid improves abnormal behavior by mitigation of oxidative stress, inflammation, ferroptosis, and tauopathy in P301S Tau transgenic mice. Redox Biol 2018; 14: 535–548

[127] Mahoney-Sánchez L, Bouchaoui H, Ayton S, Devos D, Duce JA, Devedjian JC. Ferroptosis and its potential role in the physiopathology of Parkinson’s disease. Prog Neurobiol 2021; 196: 101890

[128] Angelova PR, Choi ML, Berezhnov AV, Horrocks MH, Hughes CD, De S, Rodrigues M, Yapom R, Little D, Dolt KS, Kunath T, Devine MJ, Gissen P, Shchepinov MS, Sylantyev S, Pavlov EV, Klenerman D, Abramov AY, Gandhi S. Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation. Cell Death Differ 2020; 27(10): 2781–2796

[129] Vallerga CL, Zhang F, Fowdar J, McRae AF, Qi T, Nabais MF, Zhang Q, Kassam I, Henders AK, Wallace L, Montgomery G, Chuang YH, Horvath S, Ritz B, Halliday G, Hickie I, Kwok JB, Pearson J, Pitcher T, Kennedy M, Bentley SR, Silburn PA, Yang J, Wray NR, Lewis SJG, Anderson T, Dalrymple-Alford J, Mellick GD, Visscher PM, Gratten J. Analysis of DNA methylation associates the cystine-glutamate antiporter SLC7A11 with risk of Parkinson’s disease. Nat Commun 2020; 11(1): 1238

[130] Asanuma M, Miyazaki I. Glutathione and related molecules in Parkinsonism. Int J Mol Sci 2021; 22(16): 8689

[131] Tian Y, Lu J, Hao X, Li H, Zhang G, Liu X, Li X, Zhao C, Kuang W, Chen D, Zhu M. FTH1 inhibits ferroptosis through ferritinophagy in the 6-OHDA model of Parkinson’s disease. Neurotherapeutics 2020; 17(4): 1796–1812

[132] Bai L, Yan F, Deng R, Gu R, Zhang X, Bai J. Thioredoxin-1 rescues MPP⁺/MPTP-induced ferroptosis by increasing glutathione peroxidase 4. Mol Neurobiol 2021; 58(7): 3187–3197

[133] Devos D, Moreau C, Devedjian JC, Kluza J, Petrault M, Laloux C, Jonneaux A, Ryckewaert G, Garçon G, Rouaix N, Duhamel A, Jissendi P, Dujardin K, Auger F, Ravasi L, Hopes L, Grolez G, Firdaus W, Sablonnière B, Strubi-Vuillaume I, Zahr N, Destée A, Corvol JC, Pöltl D, Leist M, Rose C, Defebvre L, Marchetti P, Cabantchik ZI, Bordet R. Targeting chelatable iron as a therapeutic modality in Parkinson’s disease. Antioxid Redox Signal 2014; 21(2): 195–210

[134] Shi L, Huang C, Luo Q, Xia Y, Liu W, Zeng W, Cheng A, Shi R, Zhengli C. Clioquinol improves motor and non-motor deficits in MPTP-induced monkey model of Parkinson’s disease through AKT/mTOR pathway. Aging (Albany NY) 2020; 12(10): 9515–9533

[135] Huang Z, Si W, Li X, Ye S, Liu X, Ji Y, Hao X, Chen D, Zhu M. Moxibustion protects dopaminergic neurons in Parkinson’s disease through antiferroptosis. Evid Based Complement Alternat Med 2021; 2021: 6668249

[136] Lu J, Liu X, Tian Y, Li H, Ren Z, Liang S, Zhang G, Zhao C, Li X, Wang T, Chen D, Kuang W, Zhu M. Moxibustion exerts a neuroprotective effect through antiferroptosis in Parkinson’s disease. Evid Based Complement Alternat Med 2019; 2019: 2735492

[137] Brocardo PS, McGinnis E, Christie BR, Gil-Mohapel J. Time-course analysis of protein and lipid oxidation in the brains of Yac128 Huntington’s disease transgenic mice. Rejuvenation Res 2016; 19(2): 140–148

[138] Hatami A, Zhu C, Relaño-Gines A, Elias C, Galstyan A, Jun M, Milne G, Cantor CR, Chesselet MF, Shchepinov MS. Deuterium-reinforced linoleic acid lowers lipid peroxidation and mitigates cognitive impairment in the Q140 knock in mouse model of Huntington’s disease. FEBS J 2018; 285(16): 3002–3012

[139] Ribeiro M, Rosenstock TR, Cunha-Oliveira T, Ferreira IL, Oliveira CR, Rego AC. Glutathione redox cycle dysregulation in Huntington’s disease knock-in striatal cells. Free Radic Biol Med 2012; 53(10): 1857–1867

[140] Domínguez JF, Ng AC, Poudel G, Stout JC, Churchyard A, Chua P, Egan GF, Georgiou-Karistianis N. Iron accumulation in the basal ganglia in Huntington’s disease: cross-sectional data from the IMAGE-HD study. J Neurol Neurosurg Psychiatry 2016; 87(5): 545–549

[141] Tan Q, Fang Y, Gu Q. Mechanisms of modulation of ferroptosis and its role in central nervous system diseases. Front Pharmacol 2021; 12: 657033

[142] Chen J, Marks E, Lai B, Zhang Z, Duce JA, Lam LQ, Volitakis I, Bush AI, Hersch S, Fox JH. Iron accumulates in Huntington’s disease neurons: protection by deferoxamine. PLoS One 2013; 8(10): e77023

[143] Skouta R, Dixon SJ, Wang J, Dunn DE, Orman M, Shimada K, Rosenberg PA, Lo DC, Weinberg JM, Linkermann A, Stockwell BR. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J Am Chem Soc 2014; 136(12): 4551–4556

[144] Ou M, Jiang Y, Ji Y, Zhou Q, Du Z, Zhu H, Zhou Z. Role and mechanism of ferroptosis in neurological diseases. Mol Metab 2022; 61: 101502

[145] Tuo QZ, Lei P, Jackman KA, Li XL, Xiong H, Li XL, Liuyang ZY, Roisman L, Zhang ST, Ayton S, Wang Q, Crouch PJ, Ganio K, Wang XC, Pei L, Adlard PA, Lu YM, Cappai R, Wang JZ, Liu R, Bush AI. Tau-mediated iron export prevents ferroptotic damage after ischemic stroke. Mol Psychiatry 2017; 22(11): 1520–1530

[146] Tuo QZ, Masaldan S, Southon A, Mawal C, Ayton S, Bush AI, Lei P, Belaidi AA. Characterization of selenium compounds for anti-ferroptotic activity in neuronal cells and after cerebral ischemia-reperfusion injury. Neurotherapeutics 2021; 18(4): 2682–2691

[147] Tuo QZ, Liu Y, Xiang Z, Yan HF, Zou T, Shu Y, Ding XL, Zou JJ, Xu S, Tang F, Gong YQ, Li XL, Guo YJ, Zheng ZY, Deng AP, Yang ZZ, Li WJ, Zhang ST, Ayton S, Bush AI, Xu H, Dai L, Dong B, Lei P. Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion. Signal Transduct Target Ther 2022; 7(1): 59

[148] Eltzschig HK, Eckle T. Ischemia and reperfusion—from mechanism to translation. Nat Med 2011; 17(11): 1391–1401

[149] Tang LJ, Luo XJ, Tu H, Chen H, Xiong XM, Li NS, Peng J. Ferroptosis occurs in phase of reperfusion but not ischemia in rat heart following ischemia or ischemia/reperfusion. Naunyn Schmiedebergs Arch Pharmacol 2021; 394(2): 401–410

[150] Lucas DT, Szweda LI. Cardiac reperfusion injury: aging, lipid peroxidation, and mitochondrial dysfunction. Proc Natl Acad Sci U S A 1998; 95(2): 510–514

[151] Ganguly R, Hasanally D, Stamenkovic A, Maddaford TG, Chaudhary R, Pierce GN, Ravandi A. Alpha linolenic acid decreases apoptosis and oxidized phospholipids in cardiomyocytes during ischemia/reperfusion. Mol Cell Biochem 2018; 437(1–2): 163–175

[152] Yeang C, Hasanally D, Que X, Hung MY, Stamenkovic A, Chan D, Chaudhary R, Margulets V, Edel AL, Hoshijima M, Gu Y, Bradford W, Dalton N, Miu P, Cheung DY, Jassal DS, Pierce GN, Peterson KL, Kirshenbaum LA, Witztum JL, Tsimikas S, Ravandi A. Reduction of myocardial ischaemia-reperfusion injury by inactivating oxidized phospholipids. Cardiovasc Res 2019; 115(1): 179–189

[153] Stamenkovic A, O’Hara KA, Nelson DC, Maddaford TG, Edel AL, Maddaford G, Dibrov E, Aghanoori M, Kirshenbaum LA, Fernyhough P, Aliani M, Pierce GN, Ravandi A. Oxidized phosphatidylcholines trigger ferroptosis in cardiomyocytes during ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2021; 320(3): H1170–H1184

[154] Park E, Chung SW. ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation. Cell Death Dis 2019; 10(11): 822

[155] Liu H, Mo H, Yang C, Mei X, Song X, Lu W, Xiao H, Yan J, Wang X, Yan J, Luo T, Lin Y, Wen D, Chen G, Chen A, Ling Y. A novel function of ATF3 in suppression of ferroptosis in mouse heart suffered ischemia/reperfusion. Free Radic Biol Med 2022; 189: 122–135

[156] Tang LJ, Zhou YJ, Xiong XM, Li NS, Zhang JJ, Luo XJ, Peng J. Ubiquitin-specific protease 7 promotes ferroptosis via activation of the p53/TfR1 pathway in the rat hearts after ischemia/reperfusion. Free Radic Biol Med 2021; 162: 339–352

[157] Miyamoto HD, Ikeda M, Ide T, Tadokoro T, Furusawa S, Abe K, Ishimaru K, Enzan N, Sada M, Yamamoto T, Matsushima S, Koumura T, Yamada KI, Imai H, Tsutsui H. Iron overload via heme degradation in the endoplasmic reticulum triggers ferroptosis in myocardial ischemia-reperfusion injury. JACC Basic Transl Sci 2022; 7(8): 800–819

[158] Feng Y, Madungwe NB, Imam Aliagan AD, Tombo N, Bopassa JC. Liproxstatin-1 protects the mouse myocardium against ischemia/reperfusion injury by decreasing VDAC1 levels and restoring GPX4 levels. Biochem Biophys Res Commun 2019; 520(3): 606–611

[159] Wang Z, Yao M, Jiang L, Wang L, Yang Y, Wang Q, Qian X, Zhao Y, Qian J. Dexmedetomidine attenuates myocardial ischemia/reperfusion-induced ferroptosis via AMPK/GSK-3β/Nrf2 axis. Biomed Pharmacother 2022; 154: 113572

[160] Ma S, Sun L, Wu W, Wu J, Sun Z, Ren J. USP22 protects against myocardial ischemia-reperfusion injury via the SIRT1-p53/SLC7A11-dependent inhibition of ferroptosis-induced cardiomyocyte death. Front Physiol 2020; 11: 551318

[161] Gao M, Monian P, Quadri N, Ramasamy R, Jiang X. Glutaminolysis and transferrin regulate ferroptosis. Mol Cell 2015; 59(2): 298–308

[162] Chang HC, Wu R, Shang M, Sato T, Chen C, Shapiro JS, Liu T, Thakur A, Sawicki KT, Prasad SV, Ardehali H. Reduction in mitochondrial iron alleviates cardiac damage during injury. EMBO Mol Med 2016; 8(3): 247–267

[163] Aoyagi T, Kusakari Y, Xiao CY, Inouye BT, Takahashi M, Scherrer-Crosbie M, Rosenzweig A, Hara K, Matsui T. Cardiac mTOR protects the heart against ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2012; 303(1): H75–H85

[164] Baba Y, Higa JK, Shimada BK, Horiuchi KM, Suhara T, Kobayashi M, Woo JD, Aoyagi H, Marh KS, Kitaoka H, Matsui T. Protective effects of the mechanistic target of rapamycin against excess iron and ferroptosis in cardiomyocytes. Am J Physiol Heart Circ Physiol 2018; 314(3): H659–H668

[165] He P, Zhang M, Zhao M, Zhang M, Ma B, Lv H, Han Y, Wu D, Zhong Z, Zhao W. A novel polysaccharide from Chuanminshen violaceum and its protective effect against myocardial injury. Front Nutr 2022; 9: 961182

[166] Mei SL, Xia ZY, Qiu Z, Jia YF, Zhou JJ, Zhou B. Shenmai Injection attenuates myocardial ischemia/reperfusion injury by targeting Nrf2/GPX4 signalling-mediated ferroptosis. Chin J Integr Med 2022; 28(11): 983–991

[167] Fan Z, Cai L, Wang S, Wang J, Chen B. Baicalin prevents myocardial ischemia/reperfusion injury through inhibiting ACSL4 mediated ferroptosis. Front Pharmacol 2021; 12: 628988

[168] Lu H, Xiao H, Dai M, Xue Y, Zhao R. Britanin relieves ferroptosis-mediated myocardial ischaemia/reperfusion damage by upregulating GPX4 through activation of AMPK/GSK3β/Nrf2 signalling. Pharm Biol 2022; 60(1): 38–45

[169] Lin JH, Yang KT, Lee WS, Ting PC, Luo YP, Lin DJ, Wang YS, Chang JC. Xanthohumol protects the rat myocardium against ischemia/reperfusion injury-induced ferroptosis. Oxid Med Cell Longev 2022; 2022: 9523491

[170] Xu S, Wu B, Zhong B, Lin L, Ding Y, Jin X, Huang Z, Lin M, Wu H, Xu D. Naringenin alleviates myocardial ischemia/reperfusion injury by regulating the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) /System xc^–/ glutathione peroxidase 4 (GPX4) axis to inhibit ferroptosis. Bioengineered 2021; 12(2): 10924–10934

[171] Li T, Tan Y, Ouyang S, He J, Liu L. Resveratrol protects against myocardial ischemia-reperfusion injury via attenuating ferroptosis. Gene 2022; 808: 145968

[172] Shan X, Lv ZY, Yin MJ, Chen J, Wang J, Wu QN. The protective effect of cyanidin-3-glucoside on myocardial ischemia-reperfusion injury through ferroptosis. Oxid Med Cell Longev 2021; 2021: 8880141

[173] Sun W, Wu X, Yu P, Zhang Q, Shen L, Chen J, Tong H, Fan M, Shi H, Chen X. LncAABR07025387.1 enhances myocardial ischemia/reperfusion injury via miR-205/ACSL4-mediated ferroptosis. Front Cell Dev Biol 2022; 10: 672391

[174] Sun W, Shi R, Guo J, Wang H, Shen L, Shi H, Yu P, Chen X. miR-135b-3p promotes cardiomyocyte ferroptosis by targeting GPX4 and aggravates myocardial ischemia/reperfusion injury. Front Cardiovasc Med 2021; 8: 663832

[175] Zhang JK, Zhang Z, Guo ZA, Fu Y, Chen XJ, Chen WJ, Wu HF, Cui XJ. The BMSC-derived exosomal lncRNA Mir9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis. Nutr Metab Cardiovasc Dis 2022; 32(2): 515–527

[176] Miller PE, van Diepen S, Ahmad T. Acute decompensated heart failure complicated by respiratory failure. Circ Heart Fail 2019; 12(5): e006013

[177] Yang X, Kawasaki NK, Min J, Matsui T, Wang F. Ferroptosis in heart failure. J Mol Cell Cardiol 2022; 173: 141–153

[178] Chen X, Xu S, Zhao C, Liu B. Role of TLR4/NADPH oxidase 4 pathway in promoting cell death through autophagy and ferroptosis during heart failure. Biochem Biophys Res Commun 2019; 516(1): 37–43

[179] Panjrath GS, Patel V, Valdiviezo CI, Narula N, Narula J, Jain D. Potentiation of doxorubicin cardiotoxicity by iron loading in a rodent model. J Am Coll Cardiol 2007; 49(25): 2457–2464

[180] Miranda CJ, Makui H, Soares RJ, Bilodeau M, Mui J, Vali H, Bertrand R, Andrews NC, Santos MM. Hfe deficiency increases susceptibility to cardiotoxicity and exacerbates changes in iron metabolism induced by doxorubicin. Blood 2003; 102(7): 2574–2580

[181] Zheng H, Shi L, Tong C, Liu Y, Hou M. circSnx12 is involved in ferroptosis during heart failure by targeting miR-224-5p. Front Cardiovasc Med 2021; 8: 656093

[182] Fang X, Cai Z, Wang H, Han D, Cheng Q, Zhang P, Gao F, Yu Y, Song Z, Wu Q, An P, Huang S, Pan J, Chen HZ, Chen J, Linkermann A, Min J, Wang F. Loss of cardiac ferritin H facilitates cardiomyopathy via Slc7a11-mediated ferroptosis. Circ Res 2020; 127(4): 486–501

[183] Bai YT, Chang R, Wang H, Xiao FJ, Ge RL, Wang LS. ENPP2 protects cardiomyocytes from erastin-induced ferroptosis. Biochem Biophys Res Commun 2018; 499(1): 44–51

[184] Liu B, Zhao C, Li H, Chen X, Ding Y, Xu S. Puerarin protects against heart failure induced by pressure overload through mitigation of ferroptosis. Biochem Biophys Res Commun 2018; 497(1): 233–240

[185] Ma S, He LL, Zhang GR, Zuo QJ, Wang ZL, Zhai JL, Zhang TT, Wang Y, Ma HJ, Guo YF. Canagliflozin mitigates ferroptosis and ameliorates heart failure in rats with preserved ejection fraction. Naunyn Schmiedebergs Arch Pharmacol 2022; 395(8): 945–962

[186] Zhou Y, Zhou H, Hua L, Hou C, Jia Q, Chen J, Zhang S, Wang Y, He S, Jia E. Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis. Free Radic Biol Med 2021; 171: 55–68

[187] Yang K, Song H, Yin D. PDSS2 inhibits the ferroptosis of vascular endothelial cells in atherosclerosis by activating Nrf2. J Cardiovasc Pharmacol 2021; 77(6): 767–776

[188] Meng Z, Liang H, Zhao J, Gao J, Liu C, Ma X, Liu J, Liang B, Jiao X, Cao J, Wang Y. HMOX1 upregulation promotes ferroptosis in diabetic atherosclerosis. Life Sci 2021; 284: 119935

[189] Cai J, Zhang M, Liu Y, Li H, Shang L, Xu T, Chen Z, Wang F, Qiao T, Li K. Iron accumulation in macrophages promotes the formation of foam cells and development of atherosclerosis. Cell Biosci 2020; 10(1): 137

[190] Bai T, Li M, Liu Y, Qiao Z, Wang Z. Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell. Free Radic Biol Med 2020; 160: 92–102

[191] Ma TL, Zhou Y, Wang C, Wang L, Chen JX, Yang HH, Zhang CY, Zhou Y, Guan CX. Targeting ferroptosis for lung diseases: exploring novel strategies in ferroptosis-associated mechanisms. Oxid Med Cell Longev 2021; 2021: 1098970

[192] Xu Y, Li X, Cheng Y, Yang M, Wang R. Inhibition of ACSL4 attenuates ferroptotic damage after pulmonary ischemia-reperfusion. FASEB J 2020; 34(12): 16262–16275

[193] Dong H, Qiang Z, Chai D, Peng J, Xia Y, Hu R, Jiang H. Nrf2 inhibits ferroptosis and protects against acute lung injury due to intestinal ischemia reperfusion via regulating SLC7A11 and HO-1. Aging (Albany NY) 2020; 12(13): 12943–12959

[194] Qiang Z, Dong H, Xia Y, Chai D, Hu R, Jiang H. Nrf2 and STAT3 alleviates ferroptosis-mediated IIR-ALI by regulating SLC7A11. Oxid Med Cell Longev 2020; 2020: 5146982

[195] ZhouHLi FNiuJYZhongWYTangMY LinDCuiHH HuangXHChen YYWangHYTuYS. Ferroptosis was involved in the oleic acid-induced acute lung injury in mice. Acta Physiologica Sinica (Sheng Li Xue Bao) 2019; 71(5): 689–697 (in Chinese)

[196] Liu P, Feng Y, Li H, Chen X, Wang G, Xu S, Li Y, Zhao L. Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis. Cell Mol Biol Lett 2020; 25(1): 10

[197] Li Y, Cao Y, Xiao J, Shang J, Tan Q, Ping F, Huang W, Wu F, Zhang H, Zhang X. Inhibitor of apoptosis-stimulating protein of p53 inhibits ferroptosis and alleviates intestinal ischemia/reperfusion-induced acute lung injury. Cell Death Differ 2020; 27(9): 2635–2650

[198] Li J, Lu K, Sun F, Tan S, Zhang X, Sheng W, Hao W, Liu M, Lv W, Han W. Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway. J Transl Med 2021; 19(1): 96

[199] Qiu YB, Wan BB, Liu G, Wu YX, Chen D, Lu MD, Chen JL, Yu RQ, Chen DZ, Pang QF. Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis. Respir Res 2020; 21(1): 232

[200] Rabe KF, Watz H. Chronic obstructive pulmonary disease. Lancet 2017; 389(10082): 1931–1940

[201] Park EJ, Park YJ, Lee SJ, Lee K, Yoon C. Whole cigarette smoke condensates induce ferroptosis in human bronchial epithelial cells. Toxicol Lett 2019; 303: 55–66

[202] Yoshida M, Minagawa S, Araya J, Sakamoto T, Hara H, Tsubouchi K, Hosaka Y, Ichikawa A, Saito N, Kadota T, Sato N, Kurita Y, Kobayashi K, Ito S, Utsumi H, Wakui H, Numata T, Kaneko Y, Mori S, Asano H, Yamashita M, Odaka M, Morikawa T, Nakayama K, Iwamoto T, Imai H, Kuwano K. Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis. Nat Commun 2019; 10(1): 3145

[203] Wang Y, Tang M. PM2.5 induces ferroptosis in human endothelial cells through iron overload and redox imbalance. Environ Pollut 2019; 254(Pt A): 112937

[204] Meyer KC. Pulmonary fibrosis, part I: epidemiology, pathogenesis, and diagnosis. Expert Rev Respir Med 2017; 11(5): 343–359

[205] Zanoni M, Cortesi M, Zamagni A, Tesei A. The role of mesenchymal stem cells in radiation-induced lung fibrosis. Int J Mol Sci 2019; 20(16): 3876

[206] Li X, Duan L, Yuan S, Zhuang X, Qiao T, He J. Ferroptosis inhibitor alleviates radiation-induced lung fibrosis (RILF) via down-regulation of TGF-β1. J Inflamm (Lond) 2019; 16(1): 11

[207] Gong Y, Wang N, Liu N, Dong H. Lipid peroxidation and GPX4 inhibition are common causes for myofibroblast differentiation and ferroptosis. DNA Cell Biol 2019; 38(7): 725–733

[208] Rashidipour N, Karami-Mohajeri S, Mandegary A, Mohammadinejad R, Wong A, Mohit M, Salehi J, Ashrafizadeh M, Najafi A, Abiri A. Where ferroptosis inhibitors and paraquat detoxification mechanisms intersect, exploring possible treatment strategies. Toxicology 2020; 433–434: 152407

[209] Bellanti F, Villani R, Facciorusso A, Vendemiale G, Serviddio G. Lipid oxidation products in the pathogenesis of non-alcoholic steatohepatitis. Free Radic Biol Med 2017; 111: 173–185

[210] Ota T. Molecular mechanisms of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). Adv Exp Med Biol 2021; 1261: 223–229

[211] Videla LA, Valenzuela R. Perspectives in liver redox imbalance: toxicological and pharmacological aspects underlying iron overloading, nonalcoholic fatty liver disease, and thyroid hormone action. Biofactors 2022; 48(2): 400–415

[212] Tsurusaki S, Tsuchiya Y, Koumura T, Nakasone M, Sakamoto T, Matsuoka M, Imai H, Yuet-Yin Kok C, Okochi H, Nakano H, Miyajima A, Tanaka M. Hepatic ferroptosis plays an important role as the trigger for initiating inflammation in nonalcoholic steatohepatitis. Cell Death Dis 2019; 10(6): 449

[213] Wei S, Qiu T, Wang N, Yao X, Jiang L, Jia X, Tao Y, Zhang J, Zhu Y, Yang G, Liu X, Liu S, Sun X. Ferroptosis mediated by the interaction between Mfn2 and IREα promotes arsenic-induced nonalcoholic steatohepatitis. Environ Res 2020; 188: 109824

[214] Zhang XJ, Ji YX, Cheng X, Cheng Y, Yang H, Wang J, Zhao LP, Huang YP, Sun D, Xiang H, Shen LJ, Li PL, Ma JP, Tian RF, Yang J, Yao X, Xu H, Liao R, Xiao L, Zhang P, Zhang X, Zhao GN, Wang X, Hu ML, Tian S, Wan J, Cai J, Ma X, Xu Q, Wang Y, Touyz RM, Liu PP, Loomba R, She ZG, Li H. A small molecule targeting ALOX12-ACC1 ameliorates nonalcoholic steatohepatitis in mice and macaques. Sci Transl Med 2021; 13(624): eabg8116

[215] Li X, Wang TX, Huang X, Li Y, Sun T, Zang S, Guan KL, Xiong Y, Liu J, Yuan HX. Targeting ferroptosis alleviates methionine-choline deficient (MCD)-diet induced NASH by suppressing liver lipotoxicity. Liver Int 2020; 40(6): 1378–1394

[216] Qi J, Kim JW, Zhou Z, Lim CW, Kim B. Ferroptosis affects the progression of nonalcoholic steatohepatitis via the modulation of lipid peroxidation-mediated cell death in mice. Am J Pathol 2020; 190(1): 68–81

[217] Zhu Z, Zhang Y, Huang X, Can L, Zhao X, Wang Y, Xue J, Cheng M, Zhu L. Thymosin beta 4 alleviates non-alcoholic fatty liver by inhibiting ferroptosis via up-regulation of GPX4. Eur J Pharmacol 2021; 908: 174351

[218] Liu B, Yi W, Mao X, Yang L, Rao C. Enoyl coenzyme A hydratase 1 alleviates nonalcoholic steatohepatitis in mice by suppressing hepatic ferroptosis. Am J Physiol Endocrinol Metab 2021; 320(5): E925–E937

[219] Yang Y, Chen J, Gao Q, Shan X, Wang J, Lv Z. Study on the attenuated effect of ginkgolide B on ferroptosis in high fat diet induced nonalcoholic fatty liver disease. Toxicology 2020; 445: 152599

[220] Lu D, Xia Q, Yang Z, Gao S, Sun S, Luo X, Li Z, Zhang X, Han S, Li X, Cao M. ENO3 promoted the progression of NASH by negatively regulating ferroptosis via elevation of GPX4 expression and lipid accumulation. Ann Transl Med 2021; 9(8): 661

[221] Chen J, Li X, Ge C, Min J, Wang F. The multifaceted role of ferroptosis in liver disease. Cell Death Differ 2022; 29(3): 467–480

[222] Liu CY, Wang M, Yu HM, Han FX, Wu QS, Cai XJ, Kurihara H, Chen YX, Li YF, He RR. Ferroptosis is involved in alcohol-induced cell death in vivo and in vitro. Biosci Biotechnol Biochem 2020; 84(8): 1621–1628

[223] Costa-Matos L, Batista P, Monteiro N, Simões M, Egas C, Pereira J, Pinho H, Santos N, Ribeiro J, Cipriano MA, Henriques P, Girão F, Rodrigues A, Carvalho A. Liver hepcidin mRNA expression is inappropriately low in alcoholic patients compared with healthy controls. Eur J Gastroenterol Hepatol 2012; 24(10): 1158–1165

[224] Zhou Z, Ye TJ, Bonavita G, Daniels M, Kainrad N, Jogasuria A, You M. Adipose-specific lipin-1 overexpression renders hepatic ferroptosis and exacerbates alcoholic steatohepatitis in mice. Hepatol Commun 2019; 3(5): 656–669

[225] Zhou Z, Ye TJ, DeCaro E, Buehler B, Stahl Z, Bonavita G, Daniels M, You M. Intestinal SIRT1 deficiency protects mice from ethanol-induced liver injury by mitigating ferroptosis. Am J Pathol 2020; 190(1): 82–92

[226] Liu J, He H, Wang J, Guo X, Lin H, Chen H, Jiang C, Chen L, Yao P, Tang Y. Oxidative stress-dependent frataxin inhibition mediated alcoholic hepatocytotoxicity through ferroptosis. Toxicology 2020; 445: 152584

[227] Mehta KJ, Farnaud SJ, Sharp PA. Iron and liver fibrosis: mechanistic and clinical aspects. World J Gastroenterol 2019; 25(5): 521–538

[228] Tak J, Kim YS, Kim TH, Park GC, Hwang S, Kim SG. Gα₁₂ overexpression in hepatocytes by ER stress exacerbates acute liver injury via ROCK1-mediated miR-15a and ALOX12 dysregulation. Theranostics 2022; 12(4): 1570–1588

[229] Du K, Oh SH, Dutta RK, Sun T, Yang WH, Chi JT, Diehl AM. Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells but exacerbates chronic liver injury. Liver Int 2021; 41(9): 2214–2227

[230] Ho CH, Huang JH, Sun MS, Tzeng IS, Hsu YC, Kuo CY. Wild bitter melon extract regulates LPS-induced hepatic stellate cell activation, inflammation, endoplasmic reticulum stress, and ferroptosis. Evid Based Complement Alternat Med 2021; 2021: 6671129

[231] Wang L, Zhang Z, Li M, Wang F, Jia Y, Zhang F, Shao J, Chen A, Zheng S. P53-dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride-induced liver fibrosis and hepatic stellate cell activation. IUBMB Life 2019; 71(1): 45–56

[232] Li Y, Jin C, Shen M, Wang Z, Tan S, Chen A, Wang S, Shao J, Zhang F, Zhang Z, Zheng S. Iron regulatory protein 2 is required for artemether-mediated anti-hepatic fibrosis through ferroptosis pathway. Free Radic Biol Med 2020; 160: 845–859

[233] Kong Z, Liu R, Cheng Y. Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomed Pharmacother 2019; 109: 2043–2053

[234] Zhou X, Fu Y, Liu W, Mu Y, Zhang H, Chen J, Liu P. Ferroptosis in chronic liver diseases: opportunities and challenges. Front Mol Biosci 2022; 9: 928321

[235] Tonnus W, Linkermann A. The in vivo evidence for regulated necrosis. Immunol Rev 2017; 277(1): 128–149

[236] Mata-Miranda MM, Bernal-Barquero CE, Martinez-Cuazitl A, Guerrero-Robles CI, Sanchez-Monroy V, Rojas-Lopez M, Vazquez-Zapien GJ. Nephroprotective effect of embryonic stem cells reducing lipid peroxidation in kidney injury induced by cisplatin. Oxid Med Cell Longev 2019; 2019: 5420624

[237] He S, Li R, Peng Y, Wang Z, Huang J, Meng H, Min J, Wang F, Ma Q. ACSL4 contributes to ferroptosis-mediated rhabdomyolysis in exertional heat stroke. J Cachexia Sarcopenia Muscle 2022; 13(3): 1717–1730

[238] Wang Y, Zhang M, Bi R, Su Y, Quan F, Lin Y, Yue C, Cui X, Zhao Q, Liu S, Yang Y, Zhang D, Cao Q, Gao X. ACSL4 deficiency confers protection against ferroptosis-mediated acute kidney injury. Redox Biol 2022; 51: 102262

[239] Ma D, Li C, Jiang P, Jiang Y, Wang J, Zhang D. Inhibition of ferroptosis attenuates acute kidney injury in rats with severe acute pancreatitis. Dig Dis Sci 2021; 66(2): 483–492

[240] Ding C, Ding X, Zheng J, Wang B, Li Y, Xiang H, Dou M, Qiao Y, Tian P, Xue W. miR-182-5p and miR-378a-3p regulate ferroptosis in I/R-induced renal injury. Cell Death Dis 2020; 11(10): 929

[241] Leaf DE, Rajapurkar M, Lele SS, Mukhopadhyay B, Boerger EAS, Mc Causland FR, Eisenga MF, Singh K, Babitt JL, Kellum JA, Palevsky PM, Christov M, Waikar SS. Iron, hepcidin, and death in human AKI. J Am Soc Nephrol 2019; 30(3): 493–504

[242] Wang X, Zheng X, Zhang J, Zhao S, Wang Z, Wang F, Shang W, Barasch J, Qiu A. Physiological functions of ferroportin in the regulation of renal iron recycling and ischemic acute kidney injury. Am J Physiol Renal Physiol 2018; 315(4): F1042–F1057

[243] Zhang X, Li X. Abnormal iron and lipid metabolism mediated ferroptosis in kidney diseases and its therapeutic potential. Metabolites 2022; 12(1): 58

[244] Chen C, Wang D, Yu Y, Zhao T, Min N, Wu Y, Kang L, Zhao Y, Du L, Zhang M, Gong J, Zhang Z, Zhang Y, Mi X, Yue S, Tan X. Legumain promotes tubular ferroptosis by facilitating chaperone-mediated autophagy of GPX4 in AKI. Cell Death Dis 2021; 12(1): 65

[245] Wang Y, Quan F, Cao Q, Lin Y, Yue C, Bi R, Cui X, Yang H, Yang Y, Birnbaumer L, Li X, Gao X. Quercetin alleviates acute kidney injury by inhibiting ferroptosis. J Adv Res 2020; 28: 231–243

[246] Li D, Liu B, Fan Y, Liu M, Han B, Meng Y, Xu X, Song Z, Liu X, Hao Q, Duan X, Nakai A, Chang Y, Cao P, Tan K. Nuciferine protects against folic acid-induced acute kidney injury by inhibiting ferroptosis. Br J Pharmacol 2021; 178(5): 1182–1199

[247] Hu Z, Zhang H, Yi B, Yang S, Liu J, Hu J, Wang J, Cao K, Zhang W. VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis. Cell Death Dis 2020; 11(1): 73

[248] Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet 2017; 389(10075): 1238–1252

[249] Wang Y, Bi R, Quan F, Cao Q, Lin Y, Yue C, Cui X, Yang H, Gao X, Zhang D. Ferroptosis involves in renal tubular cell death in diabetic nephropathy. Eur J Pharmacol 2020; 888: 173574

[250] Kim S, Kang SW, Joo J, Han SH, Shin H, Nam BY, Park J, Yoo TH, Kim G, Lee P, Park JT. Characterization of ferroptosis in kidney tubular cell death under diabetic conditions. Cell Death Dis 2021; 12(2): 160

[251] Wu Y, Zhao Y, Yang HZ, Wang YJ, Chen Y. HMGB1 regulates ferroptosis through Nrf2 pathway in mesangial cells in response to high glucose. Biosci Rep 2021; 41(2): BSR20202924

[252] Li S, Zheng L, Zhang J, Liu X, Wu Z. Inhibition of ferroptosis by up-regulating Nrf2 delayed the progression of diabetic nephropathy. Free Radic Biol Med 2021; 162: 435–449

[253] Zhang Y, Mou Y, Zhang J, Suo C, Zhou H, Gu M, Wang Z, Tan R. Therapeutic implications of ferroptosis in renal fibrosis. Front Mol Biosci 2022; 9: 890766

[254] Yang L, Guo J, Yu N, Liu Y, Song H, Niu J, Gu Y. Tocilizumab mimotope alleviates kidney injury and fibrosis by inhibiting IL-6 signaling and ferroptosis in UUO model. Life Sci 2020; 261: 118487

[255] Zhou L, Xue X, Hou Q, Dai C. Targeting ferroptosis attenuates interstitial inflammation and kidney fibrosis. Kidney Dis (Basel) 2021; 8(1): 57–71

[256] Zhang X, Li LX, Ding H, Torres VE, Yu C, Li X. Ferroptosis promotes cyst growth in autosomal dominant polycystic kidney disease mouse models. J Am Soc Nephrol 2021; 32(11): 2759–2776

[257] Radadiya PS, Thornton MM, Puri RV, Yerrathota S, Dinh-Phan J, Magenheimer B, Subramaniam D, Tran PV, Zhu H, Bolisetty S, Calvet JP, Wallace DP, Sharma M. Ciclopirox olamine induces ferritinophagy and reduces cyst burden in polycystic kidney disease. JCI Insight 2021; 6(8): e141299

[258] Wei S, Qiu T, Yao X, Wang N, Jiang L, Jia X, Tao Y, Wang Z, Pei P, Zhang J, Zhu Y, Yang G, Liu X, Liu S, Sun X. Arsenic induces pancreatic dysfunction and ferroptosis via mitochondrial ROS-autophagy-lysosomal pathway. J Hazard Mater 2020; 384: 121390

[259] Li D, Jiang C, Mei G, Zhao Y, Chen L, Liu J, Tang Y, Gao C, Yao P. Quercetin alleviates ferroptosis of pancreatic β cells in type 2 diabetes. Nutrients 2020; 12(10): 2954

[260] Bruni A, Pepper AR, Pawlick RL, Gala-Lopez B, Gamble AF, Kin T, Seeberger K, Korbutt GS, Bornstein SR, Linkermann A, Shapiro AMJ. Ferroptosis-inducing agents compromise in vitro human islet viability and function. Cell Death Dis 2018; 9(6): 595

[261] Wang X, Fang X, Zheng W, Zhou J, Song Z, Xu M, Min J, Wang F. Genetic support of a causal relationship between iron status and type 2 diabetes: a Mendelian randomization study. J Clin Endocrinol Metab 2021; 106(11): e4641–e4651

[262] Zhou Y. The protective effects of cryptochlorogenic acid on β-cells function in diabetes in vivo and vitro via inhibition of ferroptosis. Diabetes Metab Syndr Obes 2020; 13: 1921–1931

[263] Zhang X, Jiang L, Chen H, Wei S, Yao K, Sun X, Yang G, Jiang L, Zhang C, Wang N, Wang Y, Liu X. Resveratrol protected acrolein-induced ferroptosis and insulin secretion dysfunction via ER-stress-related PERK pathway in MIN6 cells. Toxicology 2022; 465: 153048

[264] Kose T, Vera-Aviles M, Sharp PA, Latunde-Dada GO. Curcumin and (–)-epigallocatechin-3-gallate protect murine MIN6 pancreatic beta-cells against iron toxicity and erastin-induced ferroptosis. Pharmaceuticals (Basel) 2019; 12(1): 26

[265] Sha W, Hu F, Xi Y, Chu Y, Bu S. Mechanism of ferroptosis and its role in type 2 diabetes mellitus. J Diabetes Res 2021; 2021: 9999612

[266] Killion EA, Reeves AR, El Azzouny MA, Yan QW, Surujon D, Griffin JD, Bowman TA, Wang C, Matthan NR, Klett EL, Kong D, Newman JW, Han X, Lee MJ, Coleman RA, Greenberg AS. A role for long-chain acyl-CoA synthetase-4 (ACSL4) in diet-induced phospholipid remodeling and obesity-associated adipocyte dysfunction. Mol Metab 2018; 9: 43–56

[267] Segrestin B, Moreno-Navarrete JM, Seyssel K, Alligier M, Meugnier E, Nazare JA, Vidal H, Fernandez-Real JM, Laville M. Adipose tissue expansion by overfeeding healthy men alters iron gene expression. J Clin Endocrinol Metab 2019; 104(3): 688–696

[268] Ma X, Pham VT, Mori H, MacDougald OA, Shah YM, Bodary PF. Iron elevation and adipose tissue remodeling in the epididymal depot of a mouse model of polygenic obesity. PLoS One 2017; 12(6): e0179889

[269] Yan HF, Liu ZY, Guan ZA, Guo C. Deferoxamine ameliorates adipocyte dysfunction by modulating iron metabolism in ob/ob mice. Endocr Connect 2018; 7(4): 604–616

[270] Ma W, Jia L, Xiong Q, Du H. Iron overload protects from obesity by ferroptosis. Foods 2021; 10(8): 1787

[271] Stockwell BR. Ferroptosis turns 10: emerging mechanisms, physiological functions, and therapeutic applications. Cell 2022; 185(14): 2401–2421

[272] Powell LW, Seckington RC, Deugnier Y. Haemochromatosis. Lancet 2016; 388(10045): 706–716

[273] Wang H, An P, Xie E, Wu Q, Fang X, Gao H, Zhang Z, Li Y, Wang X, Zhang J, Li G, Yang L, Liu W, Min J, Wang F. Characterization of ferroptosis in murine models of hemochromatosis. Hepatology 2017; 66(2): 449–465

[274] Yang L, Wang H, Yang X, Wu Q, An P, Jin X, Liu W, Huang X, Li Y, Yan S, Shen S, Liang T, Min J, Wang F. Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms. Signal Transduct Target Ther 2020; 5(1): 138

[275] Wu A, Feng B, Yu J, Yan L, Che L, Zhuo Y, Luo Y, Yu B, Wu D, Chen D. Fibroblast growth factor 21 attenuates iron overload-induced liver injury and fibrosis by inhibiting ferroptosis. Redox Biol 2021; 46: 102131

[276] Palmer WC, Vishnu P, Sanchez W, Aqel B, Riegert-Johnson D, Seaman LAK, Bowman AW, Rivera CE. Diagnosis and management of genetic iron overload disorders. J Gen Intern Med 2018; 33(12): 2230–2236

[277] Fang X, Ardehali H, Min J, Wang F. The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease. Nat Rev Cardiol 2023; 20(1): 7–23

[278] Rivella S. Iron metabolism under conditions of ineffective erythropoiesis in β-thalassemia. Blood 2019; 133(1): 51–58

[279] Saliba A, Taher A. Iron overload in transfusion-dependent thalassemia. Hematology 2015; 20(5): 311–312

[280] Pennell DJ, Berdoukas V, Karagiorga M, Ladis V, Piga A, Aessopos A, Gotsis ED, Tanner MA, Smith GC, Westwood MA, Wonke B, Galanello R. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood 2006; 107(9): 3738–3744

[281] Casu C, Nemeth E, Rivella S. Hepcidin agonists as therapeutic tools. Blood 2018; 131(16): 1790–1794

[282] Chen KN, Guan QW, Yin XX, Wang ZJ, Zhou HH, Mao XY. Ferrostatin-1 obviates seizures and associated cognitive deficits in ferric chloride-induced posttraumatic epilepsy via suppressing ferroptosis. Free Radic Biol Med 2022; 179: 109–118

[283] Campuzano V, Montermini L, Moltò MD, Pianese L, Cossée M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, Zara F, Cañizares J, Koutnikova H, Bidichandani SI, Gellera C, Brice A, Trouillas P, De Michele G, Filla A, De Frutos R, Palau F, Patel PI, Di Donato S, Mandel JL, Cocozza S, Koenig M, Pandolfo M. Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996; 271(5254): 1423–1427

[284] Abeti R, Parkinson MH, Hargreaves IP, Angelova PR, Sandi C, Pook MA, Giunti P, Abramov AY. ‘Mitochondrial energy imbalance and lipid peroxidation cause cell death in Friedreich’s ataxia’. Cell Death Dis 2016; 7(5): e2237

[285] Gomes CM, Santos R. Neurodegeneration in Friedreich’s ataxia: from defective frataxin to oxidative stress. Oxid Med Cell Longev 2013; 2013: 487534

[286] Petit F, Drecourt A, Dussiot M, Zangarelli C, Hermine O, Munnich A, Rötig A. Defective palmitoylation of transferrin receptor triggers iron overload in Friedreich ataxia fibroblasts. Blood 2021; 137(15): 2090–2102

[287] La Rosa P, Petrillo S, Turchi R, Berardinelli F, Schirinzi T, Vasco G, Lettieri-Barbato D, Fiorenza MT, Bertini ES, Aquilano K, Piemonte F. The Nrf2 induction prevents ferroptosis in Friedreich’s ataxia. Redox Biol 2021; 38: 101791

[288] Gao L, Hua W, Tian L, Zhou X, Wang D, Yang Y, Ni G. Molecular mechanism of ferroptosis in orthopedic diseases. Cells 2022; 11(19): 2979

[289] Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012; 64(6): 1697–1707

[290] Yao X, Sun K, Yu S, Luo J, Guo J, Lin J, Wang G, Guo Z, Ye Y, Guo F. Chondrocyte ferroptosis contribute to the progression of osteoarthritis. J Orthop Translat 2020; 27: 33–43

[291] Miao Y, Chen Y, Xue F, Liu K, Zhu B, Gao J, Yin J, Zhang C, Li G. Contribution of ferroptosis and GPX4’s dual functions to osteoarthritis progression. EBioMedicine 2022; 76: 103847

[292] Zhou X, Zheng Y, Sun W, Zhang Z, Liu J, Yang W, Yuan W, Yi Y, Wang J, Liu J. D-mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF-2α-dependent manner. Cell Prolif 2021; 54(11): e13134

[293] Park-Min KH. Mechanisms involved in normal and pathological osteoclastogenesis. Cell Mol Life Sci 2018; 75(14): 2519–2528

[294] Wang X, Ma H, Sun J, Zheng T, Zhao P, Li H, Yang M. Mitochondrial ferritin deficiency promotes osteoblastic ferroptosis via mitophagy in type 2 diabetic osteoporosis. Biol Trace Elem Res 2022; 200(1): 298–307

[295] Ma H, Wang X, Zhang W, Li H, Zhao W, Sun J, Yang M. Melatonin suppresses ferroptosis induced by high glucose via activation of the Nrf2/HO-1 signaling pathway in type 2 diabetic osteoporosis. Oxid Med Cell Longev 2020; 2020: 9067610

[296] Ni S, Yuan Y, Qian Z, Zhong Z, Lv T, Kuang Y, Yu B. Hypoxia inhibits RANKL-induced ferritinophagy and protects osteoclasts from ferroptosis. Free Radic Biol Med 2021; 169: 271–282

[297] Zhang J. The osteoprotective effects of artemisinin compounds and the possible mechanisms associated with intracellular iron: a review of in vivo and in vitro studies. Environ Toxicol Pharmacol 2020; 76: 103358

[298] Lai B, Wu CH, Wu CY, Luo SF, Lai JH. Ferroptosis and autoimmune diseases. Front Immunol 2022; 13: 916664

[299] Mao C, Lei G, Zhuang L, Gan B. Ferroptosis as an important driver of lupus. Protein Cell 2022; 13(5): 313–315

[300] Zhang D, Li Y, Du C, Sang L, Liu L, Li Y, Wang F, Fan W, Tang P, Zhang S, Chen D, Wang Y, Wang X, Xie X, Jiang Z, Song Y, Guo R. Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level. J Transl Med 2022; 20(1): 363

[301] Li P, Jiang M, Li K, Li H, Zhou Y, Xiao X, Xu Y, Krishfield S, Lipsky PE, Tsokos GC, Zhang X. Glutathione peroxidase 4-regulated neutrophil ferroptosis induces systemic autoimmunity. Nat Immunol 2021; 22(9): 1107–1117

[302] Wu J, Feng Z, Chen L, Li Y, Bian H, Geng J, Zheng ZH, Fu X, Pei Z, Qin Y, Yang L, Zhao Y, Wang K, Chen R, He Q, Nan G, Jiang X, Chen ZN, Zhu P. TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models. Nat Commun 2022; 13(1): 676

[303] Ling H, Li M, Yang C, Sun S, Zhang W, Zhao L, Xu N, Zhang J, Shen Y, Zhang X, Liu C, Lu L, Wang J. Glycine increased ferroptosis via SAM-mediated GPX4 promoter methylation in rheumatoid arthritis. Rheumatology (Oxford) 2022; 61(11): 4521–4534

[304] Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol 2016; 12(1): 49–62

[305] Günther C, Neumann H, Neurath MF, Becker C. Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium. Gut 2013; 62(7): 1062–1071

[306] Mayr L, Grabherr F, Schwärzler J, Reitmeier I, Sommer F, Gehmacher T, Niederreiter L, He GW, Ruder B, Kunz KTR, Tymoszuk P, Hilbe R, Haschka D, Feistritzer C, Gerner RR, Enrich B, Przysiecki N, Seifert M, Keller MA, Oberhuber G, Sprung S, Ran Q, Koch R, Effenberger M, Tancevski I, Zoller H, Moschen AR, Weiss G, Becker C, Rosenstiel P, Kaser A, Tilg H, Adolph TE. Dietary lipids fuel GPX4-restricted enteritis resembling Crohn’s disease. Nat Commun 2020; 11(1): 1775

[307] Xu M, Tao J, Yang Y, Tan S, Liu H, Jiang J, Zheng F, Wu B. Ferroptosis involves in intestinal epithelial cell death in ulcerative colitis. Cell Death Dis 2020; 11(2): 86

[308] McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. JAMA 2021; 325(8): 765–779

[309] Luoqian J, Yang W, Ding X, Tuo QZ, Xiang Z, Zheng Z, Guo YJ, Li L, Guan P, Ayton S, Dong B, Zhang H, Hu H, Lei P. Ferroptosis promotes T-cell activation-induced neurodegeneration in multiple sclerosis. Cell Mol Immunol 2022; 19(8): 913–924

[310] White AR. Ferroptosis drives immune-mediated neurodegeneration in multiple sclerosis. Cell Mol Immunol 2023; 20(1): 112–113

[311] Li X, Chu Y, Ma R, Dou M, Li S, Song Y, Lv Y, Zhu L. Ferroptosis as a mechanism of oligodendrocyte loss and demyelination in experimental autoimmune encephalomyelitis. J Neuroimmunol 2022; 373: 577995

[312] Rayatpour A, Foolad F, Heibatollahi M, Khajeh K, Javan M. Ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve. Sci Rep 2022; 12(1): 19630

[313] Jiao L, Li X, Luo Y, Wei J, Ding X, Xiong H, Liu X, Lei P. Iron metabolism mediates microglia susceptibility in ferroptosis. Front Cell Neurosci 2022; 16: 995084

[314] Jiang Y, Mao C, Yang R, Yan B, Shi Y, Liu X, Lai W, Liu Y, Wang X, Xiao D, Zhou H, Cheng Y, Yu F, Cao Y, Liu S, Yan Q, Tao Y. EGLN1/c-Myc induced lymphoid-specific helicase inhibits ferroptosis through lipid metabolic gene expression changes. Theranostics 2017; 7(13): 3293–3305

[315] Jiang Y, He Y, Liu S, Tao Y. Chromatin remodeling factor lymphoid-specific helicase inhibits ferroptosis through lipid metabolic genes in lung cancer progression. Chin J Cancer 2017; 36(1): 82

[316] Jiang N, Zhang X, Gu X, Li X, Shang L. Progress in understanding the role of lncRNA in programmed cell death. Cell Death Discov 2021; 7(1): 30

[317] Wang M, Mao C, Ouyang L, Liu Y, Lai W, Liu N, Shi Y, Chen L, Xiao D, Yu F, Wang X, Zhou H, Cao Y, Liu S, Yan Q, Tao Y, Zhang B. Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA. Cell Death Differ 2019; 26(11): 2329–2343

[318] Yuan B, Liao F, Shi ZZ, Ren Y, Deng XL, Yang TT, Li DY, Li RF, Pu DD, Wang YJ, Tan Y, Yang Z, Zhang YH. Dihydroartemisinin inhibits the proliferation, colony formation and induces ferroptosis of lung cancer cells by inhibiting PRIM2/SLC7A11 axis. Onco Targets Ther 2020; 13: 10829–10840

[319] Chen P, Wu Q, Feng J, Yan L, Sun Y, Liu S, Xiang Y, Zhang M, Pan T, Chen X, Duan T, Zhai L, Zhai B, Wang W, Zhang R, Chen B, Han X, Li Y, Chen L, Liu Y, Huang X, Jin T, Zhang W, Luo H, Chen X, Li Y, Li Q, Li G, Zhang Q, Zhuo L, Yang Z, Tang H, Xie T, Ouyang X, Sui X. Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis. Signal Transduct Target Ther 2020; 5(1): 51

[320] Gai C, Yu M, Li Z, Wang Y, Ding D, Zheng J, Lv S, Zhang W, Li W. Acetaminophen sensitizing erastin-induced ferroptosis via modulation of Nrf2/heme oxygenase-1 signaling pathway in non-small-cell lung cancer. J Cell Physiol 2020; 235(4): 3329–3339

[321] Yang J, Zhou Y, Xie S, Wang J, Li Z, Chen L, Mao M, Chen C, Huang A, Chen Y, Zhang X, Khan NUH, Wang L, Zhou J. Metformin induces ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer. J Exp Clin Cancer Res 2021; 40(1): 206

[322] Sun D, Li YC, Zhang XY. Lidocaine promoted ferroptosis by targeting miR-382-5p/SLC7A11 axis in ovarian and breast cancer. Front Pharmacol 2021; 12: 681223

[323] Yu H, Yang C, Jian L, Guo S, Chen R, Li K, Qu F, Tao K, Fu Y, Luo F, Liu S. Sulfasalazine-induced ferroptosis in breast cancer cells is reduced by the inhibitory effect of estrogen receptor on the transferrin receptor. Oncol Rep 2019; 42(2): 826–838

[324] Gao R, Kalathur RKR, Coto-Llerena M, Ercan C, Buechel D, Shuang S, Piscuoglio S, Dill MT, Camargo FD, Christofori G, Tang F. YAP/TAZ and ATF4 drive resistance to sorafenib in hepatocellular carcinoma by preventing ferroptosis. EMBO Mol Med 2021; 13(12): e14351

[325] Kong R, Wang N, Han W, Bao W, Lu J. IFNγ-mediated repression of system xc^– drives vulnerability to induced ferroptosis in hepatocellular carcinoma cells. J Leukoc Biol 2021; 110(2): 301–314

[326] Bai T, Liang R, Zhu R, Wang W, Zhou L, Sun Y. MicroRNA-214-3p enhances erastin-induced ferroptosis by targeting ATF4 in hepatoma cells. J Cell Physiol 2020; 235(7–8): 5637–5648

[327] Lee JY, Nam M, Son HY, Hyun K, Jang SY, Kim JW, Kim MW, Jung Y, Jang E, Yoon SJ, Kim J, Kim J, Seo J, Min JK, Oh KJ, Han BS, Kim WK, Bae KH, Song J, Kim J, Huh YM, Hwang GS, Lee EW, Lee SC. Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer. Proc Natl Acad Sci U S A 2020; 117(51): 32433–32442

[328] Wang C, Shi M, Ji J, Cai Q, Zhao Q, Jiang J, Liu J, Zhang H, Zhu Z, Zhang J. Stearoyl-CoA desaturase 1 (SCD1) facilitates the growth and anti-ferroptosis of gastric cancer cells and predicts poor prognosis of gastric cancer. Aging (Albany NY) 2020; 12(15): 15374–15391

[329] Zhao L, Peng Y, He S, Li R, Wang Z, Huang J, Lei X, Li G, Ma Q. Apatinib induced ferroptosis by lipid peroxidation in gastric cancer. Gastric Cancer 2021; 24(3): 642–654

[330] Ni H, Ruan G, Sun C, Yang X, Miao Z, Li J, Chen Y, Qin H, Liu Y, Zheng L, Xing Y, Xi T, Li X. Tanshinone IIA inhibits gastric cancer cell stemness through inducing ferroptosis. Environ Toxicol 2022; 37(2): 192–200

[331] Gao Z, Deng G, Li Y, Huang H, Sun X, Shi H, Yao X, Gao L, Ju Y, Luo M. Actinidia chinensis Planch prevents proliferation and migration of gastric cancer associated with apoptosis, ferroptosis activation and mesenchymal phenotype suppression. Biomed Pharmacother 2020; 126: 110092

[332] Xu X, Zhang X, Wei C, Zheng D, Lu X, Yang Y, Luo A, Zhang K, Duan X, Wang Y. Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis. Eur J Pharm Sci 2020; 152: 105450

[333] Xia Y, Liu S, Li C, Ai Z, Shen W, Ren W, Yang X. Discovery of a novel ferroptosis inducer-talaroconvolutin A-killing colorectal cancer cells in vitro and in vivo. Cell Death Dis 2020; 11(11): 988

[334] Liu L, Yao H, Zhou X, Chen J, Chen G, Shi X, Wu G, Zhou G, He S. miR-15a-3p regulates ferroptosis via targeting glutathione peroxidase GPX4 in colorectal cancer. Mol Carcinog 2022; 61(3): 301–310

[335] Wang R, Su Q, Yin H, Wu D, Lv C, Yan Z. Inhibition of SRSF9 enhances the sensitivity of colorectal cancer to erastin-induced ferroptosis by reducing glutathione peroxidase 4 expression. Int J Biochem Cell Biol 2021; 134: 105948

[336] Storz P. KRas, ROS and the initiation of pancreatic cancer. Small GTPases 2017; 8(1): 38–42

[337] Badgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee HJ, Purohit V, Sagalovskiy IR, Ma A, Kapilian J, Firl CEM, Decker AR, Sastra SA, Palermo CF, Andrade LR, Sajjakulnukit P, Zhang L, Tolstyka ZP, Hirschhorn T, Lamb C, Liu T, Gu W, Seeley ES, Stone E, Georgiou G, Manor U, Iuga A, Wahl GM, Stockwell BR, Lyssiotis CA, Olive KP. Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science 2020; 368(6486): 85–89

[338] Yamaguchi Y, Kasukabe T, Kumakura S. Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis. Int J Oncol 2018; 52(3): 1011–1022

[339] Cui W, Zhang J, Wu D, Zhang J, Zhou H, Rong Y, Liu F, Wei B, Xu X. Ponicidin suppresses pancreatic cancer growth by inducing ferroptosis: insight gained by mass spectrometry-based metabolomics. Phytomedicine 2022; 98: 153943

Acknowledgements

The authors receive support from the National Natural Science Foundation of China (No. 31930057 to Fudi Wang and No. 31970689 to Junxia Min), the National Key R&D Program (No. 2018YFA0507801 to Junxia Min and No. 2018YFA0507802 to Fudi Wang) and the China Postdoctoral Science Foundation (No. 2022M712733 to Xue Wang). The authors thank Hao Wang (Zhengzhou University School of Public Health, China), Xuexian Fang (Hangzhou Normal University School of Public Health, China), Yingying Yu, Enjun Xie, and Xinquan Yang (Zhejiang University School of Medicine, China) for their contribution to the discussion for this review.

Compliance with ethics guidelines

Xue Wang, Ye Zhou, Junxia Min, and Fudi Wang declare that they have no conflict of interest. This manuscript is a review article, and it does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

RIGHTS & PERMISSIONS

2023 Higher Education Press