Abstract
Ferroptosis is a widely recognized process of regulated cell death linking redox state, metabolism, and human health. It is considered a defense mechanism against extensive lipid peroxidation, a complex process that may disrupt the membrane integrity, eventually leading to toxic cellular injury. Ferroptosis is controlled by iron, reactive oxygen species, and polyunsaturated fatty acids. Accumulating evidence has addressed that ferroptosis plays an unneglectable role in regulating the development and progression of multiple pathologies of the liver, including hepatocellular carcinoma, liver fibrosis, nonalcoholic steatosis, hepatic ischemia–reperfusion injury, and liver failure. This review may increase our understating of the cellular and molecular mechanisms of liver disease progression and establish the foundation of strategies for pharmacological intervention.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andrews NC, Schmidt PJ (2007) Iron homeostasis. Annu Rev Physiol 69:69–85. https://doi.org/10.1146/annurev.physiol.69.031905.164337
Bai T, Wang S, Zhao Y, Zhu R, Wang W, Sun Y (2017) Haloperidol, a sigma receptor 1 antagonist, promotes ferroptosis in hepatocellular carcinoma cells. Biochem Biophys Res Commun 491:919–925. https://doi.org/10.1016/j.bbrc.2017.07.136
Bochkov VN, Oskolkova OV, Birukov KG, Levonen AL, Binder CJ, Stockl J (2010) Generation and biological activities of oxidized phospholipids. Antioxid Redox Signal 12:1009–1059. https://doi.org/10.1089/ars.2009.2597
Bogdan AR, Miyazawa M, Hashimoto K, Tsuji Y (2016) Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem Sci 41:274–286. https://doi.org/10.1016/j.tibs.2015.11.012
Bridges RJ, Natale NR, Patel SA (2012) System Xc− cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS. Br J Pharmacol 165:20–34. https://doi.org/10.1111/j.1476-5381.2011.01480.x
Brigelius-Flohe R, Maiorino M (2013) Glutathione peroxidases. Biochim Biophys Acta 1830:3289–3303. https://doi.org/10.1016/j.bbagen.2012.11.020
Chang LC, Chiang SK, Chen SE, Yu YL, Chou RH, Chang WC (2018) Heme oxygenase-1 mediates BAY 11-7085 induced ferroptosis. Cancer Lett 416:124–137. https://doi.org/10.1016/j.canlet.2017.12.025
Cheng Z, Li Y (2007) What is responsible for the initiating chemistry of iron-mediated lipid peroxidation: an update. Chem Rev 107:748–766. https://doi.org/10.1021/cr040077w
Dixon SJ, Stockwell BR (2014) The role of iron and reactive oxygen species in cell death. Nat Chem Biol 10:9–17. https://doi.org/10.1038/nchembio.1416
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 (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–1072. https://doi.org/10.1016/j.cell.2012.03.042
Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, Thomas AG, Gleason CE, Tatonetti NP, Slusher BS, Stockwell BR (2014) Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife 3:e02523. https://doi.org/10.7554/eLife.02523
Dixon SJ, Winter GE, Musavi LS, Lee ED, Snijder B, Rebsamen M, Superti-Furga G, Stockwell BR (2015) Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem Biol 10:1604–1609. https://doi.org/10.1021/acschembio.5b00245
Dolma S, Lessnick SL, Hahn WC, Stockwell BR (2003) Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3:285–296. https://doi.org/10.1016/s1535-6108(03)00050-3
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 (2019) Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci USA 116:2672–2680. https://doi.org/10.1073/pnas.1821022116
Fatokun AA, Dawson VL, Dawson TM (2014) Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities. Br J Pharmacol 171:2000–2016. https://doi.org/10.1111/bph.12416
Feng H, Stockwell BR (2018) Unsolved mysteries: how does lipid peroxidation cause ferroptosis? PLoS Biol 16:e2006203. https://doi.org/10.1371/journal.pbio.2006203
Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, Herbach N, Aichler M, Walch A, Eggenhofer E, Basavarajappa D, Radmark O, Kobayashi S, Seibt T, Beck H, Neff F, Esposito I, Wanke R, Forster H, Yefremova O, Heinrichmeyer M, Bornkamm GW, Geissler EK, Thomas SB, Stockwell BR, O’donnell VB, Kagan VE, Schick JA, Conrad M (2014) Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol 16:1180–1191. https://doi.org/10.1038/s41568-019-0149-1
Friedmann Angeli JP, Krysko DV, Conrad M (2019) Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. Nat Rev Cancer 19:405–414. https://doi.org/10.1038/s41568-019-0149-1
Gao H, Bai Y, Jia Y, Zhao Y, Kang R, Tang D, Dai E (2018) Ferroptosis is a lysosomal cell death process. Biochem Biophys Res Commun 503:1550–1556. https://doi.org/10.1016/j.bbrc.2018.07.078
Gao M, Yi J, Zhu J, Minikes AM, Monian P, Thompson CB, Jiang X (2019) Role of mitochondria in ferroptosis. Mol Cell 73(354–363):e3. https://doi.org/10.1016/j.molcel.2018.10.042
Gaschler MM, Andia AA, Liu H, Csuka JM, Hurlocker B, Vaiana CA, Heindel DW, Zuckerman DS, Bos PH, Reznik E, Ye LF, Tyurina YY, Lin AJ, Shchepinov MS, Chan AY, Peguero-Pereira E, Fomich MA, Daniels JD, Bekish AV, Shmanai VV, Kagan VE, Mahal LK, Woerpel KA, Stockwell BR (2018a) FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation. Nat Chem Biol 14:507–515. https://doi.org/10.1038/s41589-018-0031-6
Gaschler MM, Hu F, Feng H, Linkermann A, Min W, Stockwell BR (2018b) Determination of the subcellular localization and mechanism of action of ferrostatins in suppressing ferroptosis. ACS Chem Biol 13:1013–1020. https://doi.org/10.1021/acschembio.8b00199
Guo J, Xu B, Han Q, Zhou H, Xia Y, Gong C, Dai X, Li Z, Wu G (2018) Ferroptosis: a novel anti-tumor action for cisplatin. Cancer Res Treat 50:445–460. https://doi.org/10.4143/crt.2016.572
Hassannia B, Vandenabeele P, Vanden Berghe T (2019) Targeting ferroptosis to iron out cancer. Cancer Cell 35:830–849. https://doi.org/10.1016/j.ccell.2019.04.002
Hayano M, Yang WS, Corn CK, Pagano NC, Stockwell BR (2016) Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation. Cell Death Differ 23:270–278. https://doi.org/10.1038/cdd.2015.93
Hentze MW, Muckenthaler MU, Galy B, Camaschella C (2010) Two to tango: regulation of Mammalian iron metabolism. Cell 142:24–38. https://doi.org/10.1016/j.cell.2010.06.028
Hong SH, Lee DH, Lee YS, Jo MJ, Jeong YA, Kwon WT, Choudry HA, Bartlett DL, Lee YJ (2017) Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression. Oncotarget 8:115164–115178. https://doi.org/10.18632/oncotarget.23046
Hou W, Xie Y, Song X, Sun X, Lotze MT, Zeh HJ 3rd, Kang R, Tang D (2016) Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12:1425–1428. https://doi.org/10.1080/15548627.2016.1187366
Isenman LD, Dice JF (1989) Secretion of intact proteins and peptide fragments by lysosomal pathways of protein degradation. J Biol Chem 264:21591–21596
Ishii T, Bannai S, Sugita Y (1981) Mechanism of growth stimulation of L1210 cells by 2-mercaptoethanol in vitro. Role of the mixed disulfide of 2-mercaptoethanol and cysteine. J Biol Chem 256:12387–12392
Kim WR, Lake JR, Smith JM, Schladt DP, Skeans MA, Harper AM, Wainright JL, Snyder JJ, Israni AK, Kasiske BL (2018) OPTN/SRTR 2016 annual data report: liver. Am J Transpl 18(Suppl 1):172–253. https://doi.org/10.1111/ajt.14559
Knudsen ES, Gopal P, Singal AG (2014) The changing landscape of hepatocellular carcinoma: etiology, genetics, and therapy. Am J Pathol 184:574–583. https://doi.org/10.1016/j.ajpath.2013.10.028
Kong Z, Liu R, Cheng Y (2019) Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomed Pharmacother 109:2043–2053. https://doi.org/10.1016/j.biopha.2018.11.030
Kramer L, Kodras K (2011) Detoxification as a treatment goal in hepatic failure. Liver Int 31(Suppl 3):1–4. https://doi.org/10.1111/j.1478-3231.2011.02587.x
Li Z, Agellon LB, Allen TM, Umeda M, Jewell L, Mason A, Vance DE (2006) The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metab 3:321–331. https://doi.org/10.1016/j.cmet.2006.03.007
Li Y, Feng D, Wang Z, Zhao Y, Sun R, Tian D, Liu D, Zhang F, Ning S, Yao J, Tian X (2019) Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia/reperfusion. Cell Death Differ 26:2284–2299. https://doi.org/10.1038/s41418-019-0299-4
Lin LS, Song J, Song L, Ke K, Liu Y, Zhou Z, Shen Z, Li J, Yang Z, Tang W, Niu G, Yang HH, Chen X (2018) Simultaneous fenton-like ion delivery and glutathione depletion by MnO2-based nanoagent to enhance chemodynamic therapy. Angew Chem Int Ed Engl 57:4902–4906. https://doi.org/10.1002/anie.201712027
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, De Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390. https://doi.org/10.1056/NEJMoa0708857
Louandre C, Ezzoukhry Z, Godin C, Barbare JC, Maziere JC, Chauffert B, Galmiche A (2013) Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib. Int J Cancer 133:1732–1742. https://doi.org/10.1002/ijc.28159
Louandre C, Marcq I, Bouhlal H, Lachaier E, Godin C, Saidak Z, Francois C, Chatelain D, Debuysscher V, Barbare JC, Chauffert B, Galmiche A (2015) The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells. Cancer Lett 356:971–977. https://doi.org/10.1016/j.canlet.2014.11.014
Luo Y, Han Z, Chin SM, Linn S (1994) Three chemically distinct types of oxidants formed by iron-mediated Fenton reactions in the presence of DNA. Proc Natl Acad Sci USA 91:12438–12442. https://doi.org/10.1073/pnas.91.26.12438
Marra F, Gastaldelli A, Svegliati Baroni G, Tell G, Tiribelli C (2008) Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol Med 14:72–81. https://doi.org/10.1016/j.molmed.2007.12.003
Mcbean GJ (2012) The transsulfuration pathway: a source of cysteine for glutathione in astrocytes. Amino Acids 42:199–205. https://doi.org/10.1007/s00726-011-0864-8
Mederacke I, Hsu CC, Troeger JS, Huebener P, Mu X, Dapito DH, Pradere JP, Schwabe RF (2013) Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat Commun 4:2823. https://doi.org/10.1038/ncomms3823
Mederacke I, Dapito DH, Affo S, Uchinami H, Schwabe RF (2015) High-yield and high-purity isolation of hepatic stellate cells from normal and fibrotic mouse livers. Nat Protoc 10:305–315. https://doi.org/10.1038/nprot.2015.017
Moosmann B, Behl C (2004) Selenoproteins, cholesterol-lowering drugs, and the consequences: revisiting of the mevalonate pathway. Trends Cardiovasc Med 14:273–281. https://doi.org/10.1016/j.tcm.2004.08.003
Park SJ, Cho SS, Kim KM, Yang JH, Kim JH, Jeong EH, Yang JW, Han CY, Ku SK, Cho IJ, Ki SH (2019) Protective effect of sestrin2 against iron overload and ferroptosis-induced liver injury. Toxicol Appl Pharmacol 379:114665. https://doi.org/10.1016/j.taap.2019.114665
Qi W, Li Z, Xia L, Dai J, Zhang Q, Wu C, Xu S (2019) LncRNA GABPB1-AS1 and GABPB1 regulate oxidative stress during erastin-induced ferroptosis in HepG2 hepatocellular carcinoma cells. Sci Rep 9:16185. https://doi.org/10.1038/s41598-019-52837-8
Qi J, Kim JW, Zhou Z, Lim CW, Kim B (2020) Ferroptosis affects the progression of nonalcoholic steatohepatitis via the modulation of lipid peroxidation-mediated cell death in mice. Am J Pathol 190:68–81. https://doi.org/10.1016/j.ajpath.2019.09.011
Sato H, Tamba M, Ishii T, Bannai S (1999) Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J Biol Chem 274:11455–11458. https://doi.org/10.1074/jbc.274.17.11455
Shang Y, Luo M, Yao F, Wang S, Yuan Z, Yang Y (2020) Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. Cell Signal 72:109633. https://doi.org/10.1016/j.cellsig.2020.109633
Shimada K, Skouta R, Kaplan A, Yang WS, Hayano M, Dixon SJ, Brown LM, Valenzuela CA, Wolpaw AJ, Stockwell BR (2016) Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat Chem Biol 12:497–503. https://doi.org/10.1038/nchembio.2079
Shindou H, Shimizu T (2009) Acyl-CoA: lysophospholipid acyltransferases. J Biol Chem 284:1–5. https://doi.org/10.1074/jbc.R800046200
Skouta R, Dixon SJ, Wang J, Dunn DE, Orman M, Shimada K, Rosenberg PA, Lo DC, Weinberg JM, Linkermann A, Stockwell BR (2014) Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J Am Chem Soc 136:4551–4556. https://doi.org/10.1021/ja411006a
Soupene E, Kuypers FA (2008) Mammalian long-chain acyl-CoA synthetases. Exp Biol Med 233:507–521. https://doi.org/10.3181/0710-MR-287
Sui M, Jiang X, Chen J, Yang H, Zhu Y (2018) Magnesium isoglycyrrhizinate ameliorates liver fibrosis and hepatic stellate cell activation by regulating ferroptosis signaling pathway. Biomed Pharmacother 106:125–133. https://doi.org/10.1016/j.biopha.2018.06.060
Sun X, Niu X, Chen R, He W, Chen D, Kang R, Tang D (2016a) Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis. Hepatology 64:488–500. https://doi.org/10.1002/hep.28574
Sun X, Ou Z, Chen R, Niu X, Chen D, Kang R, Tang D (2016b) Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology 63:173–184. https://doi.org/10.1002/hep.28251
Suttner DM, Dennery PA (1999) Reversal of HO-1 related cytoprotection with increased expression is due to reactive iron. FASEB J 13:1800–1809. https://doi.org/10.1096/fasebj.13.13.1800
Torii S, Shintoku R, Kubota C, Yaegashi M, Torii R, Sasaki M, Suzuki T, Mori M, Yoshimoto Y, Takeuchi T, Yamada K (2016) An essential role for functional lysosomes in ferroptosis of cancer cells. Biochem J 473:769–777. https://doi.org/10.1042/BJ20150658
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 (2019) Hepatic ferroptosis plays an important role as the trigger for initiating inflammation in nonalcoholic steatohepatitis. Cell Death Dis 10:449. https://doi.org/10.1038/s41419-019-1678-y
Verbon EH, Trapet PL, Stringlis IA, Kruijs S, Bakker P, Pieterse CMJ (2017) Iron and immunity. Annu Rev Phytopathol 55:355–375. https://doi.org/10.1146/annurev-phyto-080516-035537
Wang L, Cai H, Hu Y, Liu F, Huang S, Zhou Y, Yu J, Xu J, Wu F (2018) A pharmacological probe identifies cystathionine beta-synthase as a new negative regulator for ferroptosis. Cell Death Dis 9:1005. https://doi.org/10.1038/s41419-018-1063-2
Wang L, Zhang Z, Li M, Wang F, Jia Y, Zhang F, Shao J, Chen A, Zheng S (2019a) P53-dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride-induced liver fibrosis and hepatic stellate cell activation. IUBMB Life 71:45–56. https://doi.org/10.1002/iub.1895
Wang Y, Chen Q, Shi C, Jiao F, Gong Z (2019b) Mechanism of glycyrrhizin on ferroptosis during acute liver failure by inhibiting oxidative stress. Mol Med Rep 20:4081–4090. https://doi.org/10.3892/mmr.2019.10660
Weiwer M, Bittker JA, Lewis TA, Shimada K, Yang WS, Macpherson L, Dandapani S, Palmer M, Stockwell BR, Schreiber SL, Munoz B (2012) Development of small-molecule probes that selectively kill cells induced to express mutant RAS. Bioorg Med Chem Lett 22:1822–1826. https://doi.org/10.1016/j.bmcl.2011.09.047
Wu Z, Geng Y, Lu X, Shi Y, Wu G, Zhang M, Shan B, Pan H, Yuan J (2019) Chaperone-mediated autophagy is involved in the execution of ferroptosis. Proc Natl Acad Sci USA 116:2996–3005. https://doi.org/10.1073/pnas.1819728116
Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X, Kang R, Tang D (2016) Ferroptosis: process and function. Cell Death Differ 23:369–379. https://doi.org/10.1038/cdd.2015.158
Xu C, Bailly-Maitre B, Reed JC (2005) Endoplasmic reticulum stress: cell life and death decisions. J Clin Investig 115:2656–2664. https://doi.org/10.1172/JCI26373
Yagoda N, Von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I, Peltier JM, Boniface JJ, Smith R, Lessnick SL, Sahasrabudhe S, Stockwell BR (2007) RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447:864–868. https://doi.org/10.1038/nature05859
Yamada N, Karasawa T, Kimura H, Watanabe S, Komada T, Kamata R, Sampilvanjil A, Ito J, Nakagawa K, Kuwata H, Hara S, Mizuta K, Sakuma Y, Sata N, Takahashi M (2020a) Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure. Cell Death Dis 11:144. https://doi.org/10.1038/s41419-020-2334-2
Yamada N, Karasawa T, Wakiya T, Sadatomo A, Ito H, Kamata R, Watanabe S, Komada T, Kimura H, Sanada Y, Sakuma Y, Mizuta K, Ohno N, Sata N, Takahashi M (2020b) Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: potential role of ferroptosis. Am J Transpl 20:1606–1618. https://doi.org/10.1111/ajt.15773
Yang WS, Stockwell BR (2008) Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol 15:234–245. https://doi.org/10.1016/j.chembiol.2008.02.010
Yang WS, Stockwell BR (2016) Ferroptosis: death by lipid peroxidation. Trends Cell Biol 26:165–176. https://doi.org/10.1016/j.tcb.2015.10.014
Yang WS, Shimada K, Delva D, Patel M, Ode E, Skouta R, Stockwell BR (2012) Identification of simple compounds with microtubule-binding activity that inhibit cancer cell growth with high potency. ACS Med Chem Lett 3:35–38. https://doi.org/10.1021/ml200195s
Yang WS, Sriramaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, Brown LM, Girotti AW, Cornish VW, Schreiber SL, Stockwell BR (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156:317–331. https://doi.org/10.1016/j.cell.2013.12.010
Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR (2016) Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci USA 113:E4966–E4975. https://doi.org/10.1073/pnas.1603244113
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 (2020) Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis. Blood 136:726–739. https://doi.org/10.1182/blood.2019002907
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 (2018) BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat Cell Biol 20:1181–1192. https://doi.org/10.1038/s41556-018-0178-0
Zhang X, Du L, Qiao Y, Zheng W, Wu Q, Chen Y, Zhu G, Liu Y, Bian Z, Guo S, Yang Y, Ma L, Yu Y, Pan Q, Sun F, Wang J (2019a) Ferroptosis is governed by differential regulation of transcription in liver cancer. Redox Biol 24:101211. https://doi.org/10.1016/j.redox.2019.101211
Zhang Y, Tan H, Daniels JD, Zandkarimi F, Liu H, Brown LM, Uchida K, O’connor OA, Stockwell BR (2019b) Imidazole ketone erastin induces ferroptosis and slows tumor growth in a mouse lymphoma model. Cell Chem Biol 26(623–633):e9. https://doi.org/10.1016/j.chembiol.2019.01.008
Zhang Z, Guo M, Li Y, Shen M, Kong D, Shao J, Ding H, Tan S, Chen A, Zhang F, Zheng S (2019c) RNA-binding protein ZFP36/TTP protects against ferroptosis by regulating autophagy signaling pathway in hepatic stellate cells. Autophagy 16:1482–1505. https://doi.org/10.1080/15548627.2019.1687985
Acknowledgements
This research was supported by the National Research Foundation of Korea (NRF), funded by the Korean government (MOE) (Grant No. NRF-2019R1A2C1004636) and the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through the Agri-Bio Industry Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA; 316007-5).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there are no competing interests in this manuscript.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kim, K.M., Cho, S.S. & Ki, S.H. Emerging roles of ferroptosis in liver pathophysiology. Arch. Pharm. Res. 43, 985–996 (2020). https://doi.org/10.1007/s12272-020-01273-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-020-01273-8