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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 6
Jun.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(6): 1454-1458

Mechanism of ferroptosis and its role in liver diseases

DOI: 10.3969/j.issn.1001-5256.2021.06.049

  • Department of Hepatology, The First Hospital of Jilin University, Changchun 130021, China

  • Received Date: 2020-11-30
  • Accepted Date: 2020-12-29
  • Published Date: 2021-06-20
    Abstract
  • Ferroptosis is a newly discovered regulatory cell death induced by the accumulation of iron-dependent lipid peroxides, with the morphological manifestations of decreased mitochondrial volume, increased mitochondrial membrane density, and reduction or disappearance of mitochondria. The mechanism of ferroptosis is mainly associated with disturbance of iron metabolism, imbalance of amino acid antioxidant system, and accumulation of lipid peroxides. Studies have shown that ferroptosis plays different roles in different liver diseases, and ferroptosis can participate in the progression of various liver inflammatory diseases and inhibit the formation of liver fibrosis, the development of hepatocellular carcinoma, and sorafenib resistance. This article summarizes the advances in the mechanism of ferroptosis and its role in liver diseases, so as to provide a reference for further research and treatment of liver diseases.

     

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  • [1]
    DIXON SJ, LEMBERG KM, LAMPRECHT MR, et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072. DOI: 10.1016/j.cell.2012.03.042.
    [2]
    ZHOU Z, YE TJ, DECARO E, et al. Intestinal SIRT1 deficiency protects mice from ethanol-induced liver injury by mitigating ferroptosis[J]. Am J Pathol, 2020, 190(1): 82-92. DOI: 10.1016/j.ajpath.2019.09.012.
    [3]
    LI X, WANG TX, HUANG X, et al. Targeting ferroptosis alleviates methionine-choline deficient (MCD)-diet induced NASH by suppressing liver lipotoxicity[J]. Liver Int, 2020, 40(6): 1378-1394. DOI: 10.1111/liv.14428.
    [4]
    LÖRINCZ T, JEMNITZ K, KARDON T, et al. Ferroptosis is involved in acetaminophen induced cell death[J]. Pathol Oncol Res, 2015, 21(4): 1115-1121. DOI: 10.1007/s12253-015-9946-3.
    [5]
    LOUANDRE C, EZZOUKHRY Z, GODIN C, et al. Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib[J]. Int J Cancer, 2013, 133(7): 1732-1742. DOI: 10.1002/ijc.28159.
    [6]
    YANG WS, STOCKWELL BR. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells[J]. Chem Biol, 2008, 15(3): 234-245. DOI: 10.1016/j.chembiol.2008.02.010.
    [7]
    DOLMA S, LESSNICK SL, HAHN WC, et al. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells[J]. Cancer Cell, 2003, 3(3): 285-296. DOI: 10.1016/s1535-6108(03)00050-3.
    [8]
    YANG WS, SRIRAMARATNAM R, WELSCH ME, et al. Regulation of ferroptotic cancer cell death by GPX4[J]. Cell, 2014, 156(1-2): 317-331. DOI: 10.1016/j.cell.2013.12.010.
    [9]
    JIANG L, KON N, LI T, et al. Ferroptosis as a p53-mediated activity during tumour suppression[J]. Nature, 2015, 520(7545): 57-62. DOI: 10.1038/nature14344.
    [10]
    SATO M, KUSUMI R, HAMASHIMA S, et al. The ferroptosis inducer erastin irreversibly inhibits system xc- and synergizes with cisplatin to increase cisplatin's cytotoxicity in cancer cells[J]. Sci Rep, 2018, 8(1): 968. DOI: 10.1038/s41598-018-19213-4.
    [11]
    MANCIAS JD, WANG X, GYGI SP, et al. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy[J]. Nature, 2014, 509(7498): 105-109. DOI: 10.1038/nature13148.
    [12]
    KAGAN VE, MAO G, QU F, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis[J]. Nat Chem Biol, 2017, 13(1): 81-90. DOI: 10.1038/nchembio.2238.
    [13]
    BRUNI A, PEPPER AR, PAWLICK RL, et al. Ferroptosis-inducing agents compromise in vitro human islet viability and function[J]. Cell Death Dis, 2018, 9(6): 595. DOI: 10.1038/s41419-018-0506-0.
    [14]
    SUN X, OU Z, CHEN R, et al. Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells[J]. Hepatology, 2016, 63(1): 173-184. DOI: 10.1002/hep.28251.
    [15]
    SUN X, OU Z, XIE M, et al. HSPB1 as a novel regulator of ferroptotic cancer cell death[J]. Oncogene, 2015, 34(45): 5617-5625. DOI: 10.1038/onc.2015.32.
    [16]
    DOLL S, PRONETH B, TYURINA YY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition[J]. Nat Chem Biol, 2017, 13(1): 91-98. DOI: 10.1038/nchembio.2239.
    [17]
    DIXON SJ, WINTER GE, MUSAVI LS, et al. Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death[J]. ACS Chem Biol, 2015, 10(7): 1604-1609. DOI: 10.1021/acschembio.5b00245.
    [18]
    SHINTOKU R, TAKIGAWA Y, YAMADA K, et al. Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3[J]. Cancer Sci, 2017, 108(11): 2187-2194. DOI: 10.1111/cas.13380.
    [19]
    WANG H, AN P, XIE E, et al. Characterization of ferroptosis in murine models of hemochromatosis[J]. Hepatology, 2017, 66(2): 449-465. DOI: 10.1002/hep.29117.
    [20]
    DOSTALIKOVA-CIMBUROVA M, BALUSIKOVA K, KRATKA K, et al. Role of duodenal iron transporters and hepcidin in patients with alcoholic liver disease[J]. J Cell Mol Med, 2014, 18(9): 1840-1850. DOI: 10.1111/jcmm.12310.
    [21]
    YIN H, HU M, LIANG X, et al. Deletion of SIRT1 from hepatocytes in mice disrupts lipin-1 signaling and aggravates alcoholic fatty liver[J]. Gastroenterology, 2014, 146(3): 801-811. DOI: 10.1053/j.gastro.2013.11.008.
    [22]
    ESLAM M, NEWSOME PN, SARIN SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement[J]. J Hepatol, 2020, 73(1): 202-209. DOI: 10.1016/j.jhep.2020.03.039.
    [23]
    TSURUSAKI S, TSUCHIYA Y, KOUMURA T, et al. Hepatic ferroptosis plays an important role as the trigger for initiating inflammation in nonalcoholic steatohepatitis[J]. Cell Death Dis, 2019, 10(6): 449. DOI: 10.1038/s41419-019-1678-y.
    [24]
    ZHANG Z, YAO Z, WANG L, et al. Activation of ferritinophagy is required for the RNA-binding protein ELAVL1/HuR to regulate ferroptosis in hepatic stellate cells[J]. Autophagy, 2018, 14(12): 2083-2103. DOI: 10.1080/15548627.2018.1503146.
    [25]
    SUI M, JIANG X, CHEN J, et al. Magnesium isoglycyrrhizinate ameliorates liver fibrosis and hepatic stellate cell activation by regulating ferroptosis signaling pathway[J]. Biomed Pharmacother, 2018, 106: 125-133. DOI: 10.1016/j.biopha.2018.06.060.
    [26]
    ZHANG X, SUI S, WANG L, et al. Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin[J]. J Cell Physiol, 2020, 235(4): 3425-3437. DOI: 10.1002/jcp.29232.
    [27]
    TANG H, CHEN D, LI C, et al. Dual GSH-exhausting sorafenib loaded manganese-silica nanodrugs for inducing the ferroptosis of hepatocellular carcinoma cells[J]. Int J Pharm, 2019, 572: 118782. DOI: 10.1016/j.ijpharm.2019.118782.
    [28]
    OU Y, WANG SJ, LI D, et al. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses[J]. Proc Natl Acad Sci U S A, 2016, 113(44): e6806-e6812. DOI: 10.1073/pnas.1607152113.
    [29]
    GAO M, MONIAN P, QUADRI N, et al. Glutaminolysis and transferrin regulate ferroptosis[J]. Mol Cell, 2015, 59(2): 298-308. DOI: 10.1016/j.molcel.2015.06.011.
    [30]
    YUAN H, LI X, ZHANG X, et al. CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation[J]. Biochem Biophys Res Commun, 2016, 478(2): 838-844. DOI: 10.1016/j.bbrc.2016.08.034.
    [31]
    BAI T, LIANG R, ZHU R, et al. MicroRNA-214-3p enhances erastin-induced ferroptosis by targeting ATF4 in hepatoma cells[J]. J Cell Physiol, 2020, 235(7-8): 5637-5648. DOI: 10.1002/jcp.29496.
    [32]
    ZHANG Y, SHI J, LIU X, et al. BAP1 links metabolic regulation of ferroptosis to tumour suppression[J]. Nat Cell Biol, 2018, 20(10): 1181-1192. DOI: 10.1038/s41556-018-0178-0.
    [33]
    ZHANG X, DU L, QIAO Y, et al. Ferroptosis is governed by differential regulation of transcription in liver cancer[J]. Redox Biol, 2019, 24: 101211. DOI: 10.1016/j.redox.2019.101211.
    [34]
    SUN X, NIU X, CHEN R, et al. Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis[J]. Hepatology, 2016, 64(2): 488-500. DOI: 10.1002/hep.28574.
    [35]
    BAI T, LEI P, ZHOU H, et al. Sigma-1 receptor protects against ferroptosis in hepatocellular carcinoma cells[J]. J Cell Mol Med, 2019, 23(11): 7349-7359. DOI: 10.1111/jcmm.14594.
    [36]
    BAI T, WANG S, ZHAO Y, et al. Haloperidol, a sigma receptor 1 antagonist, promotes ferroptosis in hepatocellular carcinoma cells[J]. Biochem Biophys Res Commun, 2017, 491(4): 919-925. DOI: 10.1016/j.bbrc.2017.07.136.
    [37]
    SAUZAY C, LOUANDRE C, BODEAU S, et al. Protein biosynthesis, a target of sorafenib, interferes with the unfolded protein response (UPR) and ferroptosis in hepatocellular carcinoma cells[J]. Oncotarget, 2018, 9(9): 8400-8414. DOI: 10.18632/oncotarget.23843.
    [38]
    LOUANDRE C, MARCQ I, BOUHLAL H, et al. The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells[J]. Cancer Lett, 2015, 356(2 Pt B): 971-977. DOI: 10.1016/j.canlet.2014.11.014.
    [39]
    DENG G, LI Y, MA S, et al. Caveolin-1 dictates ferroptosis in the execution of acute immune-mediated hepatic damage by attenuating nitrogen stress[J]. Free Radic Biol Med, 2020, 148: 151-161. DOI: 10.1016/j.freeradbiomed.2019.12.026.
    [40]
    KAIN HS, GLENNON E, VIJAYAN K, et al. Liver stage malaria infection is controlled by host regulators of lipid peroxidation[J]. Cell Death Differ, 2020, 27(1): 44-54. DOI: 10.1038/s41418-019-0338-1.
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