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Semin Liver Dis
DOI: 10.1055/a-2576-4332
Invited Review

The Ways to Die: Cell Death in Liver Pathophysiology

Peng Cao
1   Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas
,
Hartmut Jaeschke
1   Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas
,
Hong-Min Ni
1   Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas
,
Wen-Xing Ding
1   Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas
2   Division of Gastroenterology, Hepatology and Mobility, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas
› Author Affiliations Funding This study was supported in part by the National Institute of Health (NIH) funds R37 AA020518, R21 AA030617, R01AA031230 (W.X.D.) and R01DK134737 (H.M.N.).
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Abstract

Liver diseases are closely associated with various cell death mechanisms, including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. Each process contributes uniquely to the pathophysiology of liver injury and repair. Importantly, these mechanisms are not limited to hepatocytes; they also significantly involve nonparenchymal cells. This review examines the molecular pathways and regulatory mechanisms underlying these forms of cell death in hepatocytes, emphasizing their roles in several liver diseases, such as ischemia–reperfusion injury, metabolic dysfunction-associated steatotic liver disease, drug-induced liver injury, and alcohol-associated liver disease. Recent insights into ferroptosis and pyroptosis may reveal novel therapeutic targets for managing liver diseases. This review aims to provide a comprehensive overview of these cell death mechanisms in the context of liver diseases, detailing their molecular signaling pathways and implications for potential treatment strategies.

Keywords

apoptosis - autophagy - ferroptosis - necroptosis - pyropotsis

Author Contributions

P.C., H.J., H.M.N., and W.X.D. conceived and wrote the manuscript. W.X.D. created the graphs and figures using Biorender. P.C. compiled the table.




Publication History

Accepted Manuscript online:
08 April 2025

Article published online:
28 April 2025

© 2025. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
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  • References

  • 1 Yuan J, Ofengeim D. A guide to cell death pathways. Nat Rev Mol Cell Biol 2024; 25 (05) 379-395
    PubMedSearch in Google Scholar
  • 2 Galluzzi L, Vitale I, Aaronson SA. et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 2018; 25 (03) 486-541
    CrossrefPubMedSearch in Google Scholar
  • 3 Kayagaki N, Kornfeld OS, Lee BL. et al. NINJ1 mediates plasma membrane rupture during lytic cell death. Nature 2021; 591 (7848) 131-136
    PubMedSearch in Google Scholar
  • 4 Conradt B, Miao EA, Yuan J. et al. The story behind the emergence of different forms of cell death. Dev Cell 2024; 59 (19) 2519-2522
    PubMedSearch in Google Scholar
  • 5 David L, Borges JP, Hollingsworth LR. et al. NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks. Cell 2024; 187 (09) 2224-2235.e16
    PubMedSearch in Google Scholar
  • 6 Luedde T, Kaplowitz N, Schwabe RF. Cell death and cell death responses in liver disease: mechanisms and clinical relevance. Gastroenterology 2014; 147 (04) 765-783.e4
    PubMedSearch in Google Scholar
  • 7 Shojaie L, Iorga A, Dara L. Cell death in liver diseases: a review. Int J Mol Sci 2020; 21 (24) 21
    CrossrefPubMedSearch in Google Scholar
  • 8 Wang S, Pacher P, De Lisle RC, Huang H, Ding WX. A mechanistic review of cell death in alcohol-induced liver injury. Alcohol Clin Exp Res 2016; 40 (06) 1215-1223
    PubMedSearch in Google Scholar
  • 9 Miyata T, Nagy LE. Programmed cell death in alcohol-associated liver disease. Clin Mol Hepatol 2020; 26 (04) 618-625
    CrossrefPubMedSearch in Google Scholar
  • 10 Qian H, Chao X, Williams J. et al. Autophagy in liver diseases: a review. Mol Aspects Med 2021; 82: 100973
    PubMedSearch in Google Scholar
  • 11 Ma X, McKeen T, Zhang J, Ding WX. Role and mechanisms of mitophagy in liver diseases. Cells 2020; 9 (04) 9
    CrossrefPubMedSearch in Google Scholar
  • 12 Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26 (04) 239-257
    PubMedSearch in Google Scholar
  • 13 Nössing C, Ryan KM. 50 years on and still very much alive: 'Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics'. Br J Cancer 2023; 128 (03) 426-431
    PubMedSearch in Google Scholar
  • 14 Li J, Yuan J. Caspases in apoptosis and beyond. Oncogene 2008; 27 (48) 6194-6206
    PubMedSearch in Google Scholar
  • 15 Sahoo G, Samal D, Khandayataray P, Murthy MK. A review on caspases: key regulators of biological activities and apoptosis. Mol Neurobiol 2023; 60 (10) 5805-5837
    PubMedSearch in Google Scholar
  • 16 Yin XM, Ding WX. Death receptor activation-induced hepatocyte apoptosis and liver injury. Curr Mol Med 2003; 3 (06) 491-508
    PubMedSearch in Google Scholar
  • 17 Li P, Nijhawan D, Budihardjo I. et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91 (04) 479-489
    PubMedSearch in Google Scholar
  • 18 Scorrano L, Korsmeyer SJ. Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochem Biophys Res Commun 2003; 304 (03) 437-444
    PubMedSearch in Google Scholar
  • 19 Czabotar PE, Garcia-Saez AJ. Mechanisms of BCL-2 family proteins in mitochondrial apoptosis. Nat Rev Mol Cell Biol 2023; 24 (10) 732-748
    PubMedSearch in Google Scholar
  • 20 Sinha S, Levine B. The autophagy effector Beclin 1: a novel BH3-only protein. Oncogene 2008; 27 (Suppl 1, Suppl 1): S137-S148
    PubMedSearch in Google Scholar
  • 21 Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J 1999; 341 (Pt 2): 233-249
    PubMedSearch in Google Scholar
  • 22 Ma X, Niu M, Ni HM, Ding WX. Mitochondrial dynamics, quality control, and mtDNA in alcohol-associated liver disease and liver cancer. Hepatology 2024;
    CrossrefPubMedSearch in Google Scholar
  • 23 Kim J, Gupta R, Blanco LP. et al. VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease. Science 2019; 366 (6472) 1531-1536
    CrossrefPubMedSearch in Google Scholar
  • 24 Motwani M, Pesiridis S, Fitzgerald KA. DNA sensing by the cGAS-STING pathway in health and disease. Nat Rev Genet 2019; 20 (11) 657-674
    CrossrefPubMedSearch in Google Scholar
  • 25 Ablasser A, Goldeck M, Cavlar T. et al. cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING. Nature 2013; 498 (7454) 380-384
    PubMedSearch in Google Scholar
  • 26 Malhi H, Guicciardi ME, Gores GJ. Hepatocyte death: a clear and present danger. Physiol Rev 2010; 90 (03) 1165-1194
    PubMedSearch in Google Scholar
  • 27 Malhi H, Gores GJ, Lemasters JJ. Apoptosis and necrosis in the liver: a tale of two deaths?. Hepatology 2006; 43 (2, Suppl 1): S31-S44
    CrossrefPubMedSearch in Google Scholar
  • 28 Degterev A, Huang Z, Boyce M. et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 2005; 1 (02) 112-119
    PubMedSearch in Google Scholar
  • 29 Zhang DW, Shao J, Lin J. et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 2009; 325 (5938) 332-336
    PubMedSearch in Google Scholar
  • 30 Cho YS, Challa S, Moquin D. et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 2009; 137 (06) 1112-1123
    CrossrefPubMedSearch in Google Scholar
  • 31 He S, Wang L, Miao L. et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 2009; 137 (06) 1100-1111
    PubMedSearch in Google Scholar
  • 32 Vucic D, Dixit VM, Wertz IE. Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death. Nat Rev Mol Cell Biol 2011; 12 (07) 439-452
    PubMedSearch in Google Scholar
  • 33 Zhou Z, Han V, Han J. New components of the necroptotic pathway. Protein Cell 2012; 3 (11) 811-817
    PubMedSearch in Google Scholar
  • 34 Ding WX, Yin XM. Dissection of the multiple mechanisms of TNF-alpha-induced apoptosis in liver injury. J Cell Mol Med 2004; 8 (04) 445-454
    PubMedSearch in Google Scholar
  • 35 Vandenabeele P, Declercq W, Van Herreweghe F, Vanden Berghe T. The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci Signal 2010; 3 (115) re4
    PubMedSearch in Google Scholar
  • 36 Weinlich R, Green DR. The two faces of receptor interacting protein kinase-1. Mol Cell 2014; 56 (04) 469-480
    PubMedSearch in Google Scholar
  • 37 Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol 2014; 15 (02) 135-147
    CrossrefPubMedSearch in Google Scholar
  • 38 Dillon CP, Weinlich R, Rodriguez DA. et al. RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3. Cell 2014; 157 (05) 1189-1202
    PubMedSearch in Google Scholar
  • 39 Mandal P, Berger SB, Pillay S. et al. RIP3 induces apoptosis independent of pronecrotic kinase activity. Mol Cell 2014; 56 (04) 481-495
    CrossrefPubMedSearch in Google Scholar
  • 40 Tenev T, Bianchi K, Darding M. et al. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol Cell 2011; 43 (03) 432-448
    PubMedSearch in Google Scholar
  • 41 Newton K, Dugger DL, Wickliffe KE. et al. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science 2014; 343 (6177) 1357-1360
    PubMedSearch in Google Scholar
  • 42 Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol 2001; 9 (03) 113-114
    PubMedSearch in Google Scholar
  • 43 Labbé K, Saleh M. Cell death in the host response to infection. Cell Death Differ 2008; 15 (09) 1339-1349
    PubMedSearch in Google Scholar
  • 44 Vande Walle L, Lamkanfi M. Pyroptosis. Curr Biol 2016; 26 (13) R568-R572
    PubMedSearch in Google Scholar
  • 45 Liu X, Zhang Z, Ruan J. et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 2016; 535 (7610) 153-158
    CrossrefPubMedSearch in Google Scholar
  • 46 Privitera G, Rana N, Armuzzi A, Pizarro TT. The gasdermin protein family: emerging roles in gastrointestinal health and disease. Nat Rev Gastroenterol Hepatol 2023; 20 (06) 366-387
    PubMedSearch in Google Scholar
  • 47 Gaidt MM, Hornung V. Pore formation by GSDMD is the effector mechanism of pyroptosis. EMBO J 2016; 35 (20) 2167-2169
    PubMedSearch in Google Scholar
  • 48 Knorr J, Wree A, Feldstein AE. Pyroptosis in steatohepatitis and liver diseases. J Mol Biol 2022; 434 (04) 167271
    PubMedSearch in Google Scholar
  • 49 Dixon SJ, Lemberg KM, Lamprecht MR. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 2012; 149 (05) 1060-1072
    CrossrefPubMedSearch in Google Scholar
  • 50 Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol 2021; 22 (04) 266-282
    CrossrefPubMedSearch in Google Scholar
  • 51 Dai E, Chen X, Linkermann A. et al. A guideline on the molecular ecosystem regulating ferroptosis. Nat Cell Biol 2024; 26 (09) 1447-1457
    PubMedSearch in Google Scholar
  • 52 Brown AR, Hirschhorn T, Stockwell BR. Ferroptosis-disease perils and therapeutic promise. Science 2024; 386 (6724) 848-849
    PubMedSearch in Google Scholar
  • 53 Stockwell BR, Jiang X, Gu W. Emerging mechanisms and disease relevance of ferroptosis. Trends Cell Biol 2020; 30 (06) 478-490
    PubMedSearch in Google Scholar
  • 54 Galy B, Conrad M, Muckenthaler M. Mechanisms controlling cellular and systemic iron homeostasis. Nat Rev Mol Cell Biol 2024; 25 (02) 133-155
    CrossrefPubMedSearch in Google Scholar
  • 55 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 (02) 838-844
    PubMedSearch in Google Scholar
  • 56 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
    PubMedSearch in Google Scholar
  • 57 Hou W, Xie Y, Song X. et al. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 2016; 12 (08) 1425-1428
    PubMedSearch in Google Scholar
  • 58 Mancias JD, Wang X, Gygi SP, Harper JW, Kimmelman AC. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 2014; 509 (7498) 105-109
    PubMedSearch in Google Scholar
  • 59 Ma S, Henson ES, Chen Y, Gibson SB. Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis 2016; 7 (07) e2307
    PubMedSearch in Google Scholar
  • 60 Brown CW, Amante JJ, Chhoy P. et al. Prominin2 drives ferroptosis resistance by stimulating iron export. Dev Cell 2019; 51 (05) 575-586.e4
    PubMedSearch in Google Scholar
  • 61 Liu J, Kang R, Tang D. Signaling pathways and defense mechanisms of ferroptosis. FEBS J 2022; 289 (22) 7038-7050
    CrossrefPubMedSearch in Google Scholar
  • 62 Gan B. ACSL4, PUFA, and ferroptosis: new arsenal in anti-tumor immunity. Signal Transduct Target Ther 2022; 7 (01) 128
    PubMedSearch in Google Scholar
  • 63 Reed A, Ichu TA, Milosevich N. et al. LPCAT3 inhibitors remodel the polyunsaturated phospholipid content of human cells and protect from ferroptosis. ACS Chem Biol 2022; 17 (06) 1607-1618
    PubMedSearch in Google Scholar
  • 64 Ursini F, Maiorino M. Lipid peroxidation and ferroptosis: the role of GSH and GPx4. Free Radic Biol Med 2020; 152: 175-185
    CrossrefPubMedSearch in Google Scholar
  • 65 Ma T, Du J, Zhang Y, Wang Y, Wang B, Zhang T. GPX4-independent ferroptosis-a new strategy in disease's therapy. Cell Death Discov 2022; 8 (01) 434
    PubMedSearch in Google Scholar
  • 66 Ma X, Ni HM, Ding WX. Perspectives of mitochondria-lysosome-related organelle in hepatocyte dedifferentiation and implications in chronic liver disease. eGastroenterology 2024; 2 (01) 2
    PubMedSearch in Google Scholar
  • 67 Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008; 451 (7182) 1069-1075
    CrossrefPubMedSearch in Google Scholar
  • 68 Ding WX, Ma X, Kim S, Wang S, Ni HM. Recent insights about autophagy in pancreatitis. eGastroenterology 2024; 2 (02) 2
    PubMedSearch in Google Scholar
  • 69 Kaushik S, Cuervo AM. The coming of age of chaperone-mediated autophagy. Nat Rev Mol Cell Biol 2018; 19 (06) 365-381
    PubMedSearch in Google Scholar
  • 70 Johansen T, Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy 2011; 7 (03) 279-296
    PubMedSearch in Google Scholar
  • 71 Kirkin V, Rogov VV. A diversity of selective autophagy receptors determines the specificity of the autophagy pathway. Mol Cell 2019; 76 (02) 268-285
    PubMedSearch in Google Scholar
  • 72 Lamark T, Johansen T. Mechanisms of selective autophagy. Annu Rev Cell Dev Biol 2021; 37: 143-169
    PubMedSearch in Google Scholar
  • 73 Czaja MJ, Ding WX, Donohue Jr TM. et al. Functions of autophagy in normal and diseased liver. Autophagy 2013; 9 (08) 1131-1158
    PubMedSearch in Google Scholar
  • 74 Zhang C, Chen H, Rodriguez Y. et al. A perspective on autophagy and transcription factor EB in alcohol-associated Alzheimer's disease. Biochem Pharmacol 2023; 213: 115576
    PubMedSearch in Google Scholar
  • 75 Aman Y, Schmauck-Medina T, Hansen M. et al. Autophagy in healthy aging and disease. Nat Aging 2021; 1 (08) 634-650
    CrossrefPubMedSearch in Google Scholar
  • 76 Bialik S, Dasari SK, Kimchi A. Autophagy-dependent cell death - where, how and why a cell eats itself to death. J Cell Sci 2018; 131 (18) 131
    CrossrefPubMedSearch in Google Scholar
  • 77 Denton D, Kumar S. Autophagy-dependent cell death. Cell Death Differ 2019; 26 (04) 605-616
    PubMedSearch in Google Scholar
  • 78 Young MM, Takahashi Y, Khan O. et al. Autophagosomal membrane serves as platform for intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. J Biol Chem 2012; 287 (15) 12455-12468
    PubMedSearch in Google Scholar
  • 79 Goodall ML, Fitzwalter BE, Zahedi S. et al. The autophagy machinery controls cell death switching between apoptosis and necroptosis. Dev Cell 2016; 37 (04) 337-349
    PubMedSearch in Google Scholar
  • 80 Koenig U, Robenek H, Barresi C. et al. Cell death induced autophagy contributes to terminal differentiation of skin and skin appendages. Autophagy 2020; 16 (05) 932-945
    PubMedSearch in Google Scholar
  • 81 Ni HM, Woolbright BL, Williams J. et al. Nrf2 promotes the development of fibrosis and tumorigenesis in mice with defective hepatic autophagy. J Hepatol 2014; 61 (03) 617-625
    PubMedSearch in Google Scholar
  • 82 Khambu B, Huda N, Chen X. et al. HMGB1 promotes ductular reaction and tumorigenesis in autophagy-deficient livers. J Clin Invest 2018; 128 (06) 2419-2435
    PubMedSearch in Google Scholar
  • 83 Takamura A, Komatsu M, Hara T. et al. Autophagy-deficient mice develop multiple liver tumors. Genes Dev 2011; 25 (08) 795-800
    CrossrefPubMedSearch in Google Scholar
  • 84 Ni HM, Chao X, Yang H. et al. Dual roles of mammalian target of rapamycin in regulating liver injury and tumorigenesis in autophagy-defective mouse liver. Hepatology 2019; 70 (06) 2142-2155
    PubMedSearch in Google Scholar
  • 85 Jaeschke H, Lemasters JJ. Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury. Gastroenterology 2003; 125 (04) 1246-1257
    PubMedSearch in Google Scholar
  • 86 Yang M, Antoine DJ, Weemhoff JL. et al. Biomarkers distinguish apoptotic and necrotic cell death during hepatic ischemia/reperfusion injury in mice. Liver Transpl 2014; 20 (11) 1372-1382
    PubMedSearch in Google Scholar
  • 87 Ni HM, Chao X, Kaseff J. et al. Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis contributes to ischemia-reperfusion injury of steatotic livers. Am J Pathol 2019; 189 (07) 1363-1374
    PubMedSearch in Google Scholar
  • 88 Sasaki H, Matsuno T, Tanaka N, Orita K. Activation of apoptosis during the reperfusion phase after rat liver ischemia. Transplant Proc 1996; 28 (03) 1908-1909
    PubMedSearch in Google Scholar
  • 89 Borghi-Scoazec G, Scoazec JY, Durand F. et al. Apoptosis after ischemia-reperfusion in human liver allografts. Liver Transpl Surg 1997; 3 (04) 407-415
    PubMedSearch in Google Scholar
  • 90 Nakagawa T, Shimizu S, Watanabe T. et al. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 2005; 434 (7033) 652-658
    PubMedSearch in Google Scholar
  • 91 Uehara T, Bennett B, Sakata ST. et al. JNK mediates hepatic ischemia reperfusion injury. J Hepatol 2005; 42 (06) 850-859
    PubMedSearch in Google Scholar
  • 92 Kohli V, Madden JF, Bentley RC, Clavien PA. Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis. Gastroenterology 1999; 116 (01) 168-178
    PubMedSearch in Google Scholar
  • 93 Saeed WK, Jun DW, Jang K, Chae YJ, Lee JS, Kang HT. Does necroptosis have a crucial role in hepatic ischemia-reperfusion injury?. PLoS One 2017; 12 (09) e0184752
    PubMedSearch in Google Scholar
  • 94 Cao P, Wu Y, Li Y. et al. The important role of glycerophospholipid metabolism in the protective effects of polyphenol-enriched Tartary buckwheat extract against alcoholic liver disease. Food Funct 2022; 13 (20) 10415-10425
    PubMedSearch in Google Scholar
  • 95 Wu Y, Jiao H, Yue Y. et al. Ubiquitin ligase E3 HUWE1/MULE targets transferrin receptor for degradation and suppresses ferroptosis in acute liver injury. Cell Death Differ 2022; 29 (09) 1705-1718
    PubMedSearch in Google Scholar
  • 96 Fang X, Zhang J, Li Y. et al. Malic enzyme 1 as a novel anti-ferroptotic regulator in hepatic ischemia/reperfusion injury. Adv Sci (Weinh) 2023; 10 (13) e2205436
    PubMedSearch in Google Scholar
  • 97 Yamada N, Karasawa T, Wakiya T. et al. Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: potential role of ferroptosis. Am J Transplant 2020; 20 (06) 1606-1618
    PubMedSearch in Google Scholar
  • 98 Yamada N, Karasawa T, Ito J. et al. Inhibition of 7-dehydrocholesterol reductase prevents hepatic ferroptosis under an active state of sterol synthesis. Nat Commun 2024; 15 (01) 2195
    PubMedSearch in Google Scholar
  • 99 Jia KW, Yao RQ, Fan YW. et al. Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis. Mil Med Res 2024; 11 (01) 22
    PubMedSearch in Google Scholar
  • 100 Guo J, Song Z, Yu J. et al. Hepatocyte-specific TMEM16A deficiency alleviates hepatic ischemia/reperfusion injury via suppressing GPX4-mediated ferroptosis. Cell Death Dis 2022; 13 (12) 1072
    PubMedSearch in Google Scholar
  • 101 Li C, Wu Y, Chen K. et al. Gp78 deficiency in hepatocytes alleviates hepatic ischemia-reperfusion injury via suppressing ACSL4-mediated ferroptosis. Cell Death Dis 2023; 14 (12) 810
    PubMedSearch in Google Scholar
  • 102 Wu S, Yang J, Sun G. et al. Macrophage extracellular traps aggravate iron overload-related liver ischaemia/reperfusion injury. Br J Pharmacol 2021; 178 (18) 3783-3796
    PubMedSearch in Google Scholar
  • 103 Andrade RJ, Chalasani N, Björnsson ES. et al. Drug-induced liver injury. Nat Rev Dis Primers 2019; 5 (01) 58
    CrossrefPubMedSearch in Google Scholar
  • 104 Yuan L, Kaplowitz N. Mechanisms of drug-induced liver injury. Clin Liver Dis 2013; 17 (04) 507-518, vii vii
    PubMedSearch in Google Scholar
  • 105 Segovia-Zafra A, Di Zeo-Sánchez DE, López-Gómez C. et al. Preclinical models of idiosyncratic drug-induced liver injury (iDILI): moving towards prediction. Acta Pharm Sin B 2021; 11 (12) 3685-3726
    PubMedSearch in Google Scholar
  • 106 Teschke R, Uetrecht J. Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues. Ann Transl Med 2021; 9 (08) 730
    PubMedSearch in Google Scholar
  • 107 Hinson JA, Roberts DW, James LP. Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol 2010; (196) 369-405
    PubMedSearch in Google Scholar
  • 108 McGill MR, Sharpe MR, Williams CD, Taha M, Curry SC, Jaeschke H. The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J Clin Invest 2012; 122 (04) 1574-1583
    PubMedSearch in Google Scholar
  • 109 Jaeschke H, Ramachandran A, Chao X, Ding WX. Emerging and established modes of cell death during acetaminophen-induced liver injury. Arch Toxicol 2019; 93 (12) 3491-3502
    PubMedSearch in Google Scholar
  • 110 Gujral JS, Knight TR, Farhood A, Bajt ML, Jaeschke H. Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis?. Toxicol Sci 2002; 67 (02) 322-328
    PubMedSearch in Google Scholar
  • 111 Jaeschke H, Duan L, Akakpo JY, Farhood A, Ramachandran A. The role of apoptosis in acetaminophen hepatotoxicity. Food Chem Toxicol 2018; 118: 709-718
    PubMedSearch in Google Scholar
  • 112 Cover C, Mansouri A, Knight TR. et al. Peroxynitrite-induced mitochondrial and endonuclease-mediated nuclear DNA damage in acetaminophen hepatotoxicity. J Pharmacol Exp Ther 2005; 315 (02) 879-887
    PubMedSearch in Google Scholar
  • 113 Bajt ML, Farhood A, Lemasters JJ, Jaeschke H. Mitochondrial bax translocation accelerates DNA fragmentation and cell necrosis in a murine model of acetaminophen hepatotoxicity. J Pharmacol Exp Ther 2008; 324 (01) 8-14
    PubMedSearch in Google Scholar
  • 114 Cao P, Zhang Y, Huang Z. et al. The preventative effects of procyanidin on binge ethanol-induced lipid accumulation and ROS overproduction via the promotion of hepatic autophagy. Mol Nutr Food Res 2019; 63 (18) e1801255
    PubMedSearch in Google Scholar
  • 115 Knight TR, Jaeschke H. Acetaminophen-induced inhibition of Fas receptor-mediated liver cell apoptosis: mitochondrial dysfunction versus glutathione depletion. Toxicol Appl Pharmacol 2002; 181 (02) 133-141
    PubMedSearch in Google Scholar
  • 116 Yang X, Chao X, Wang ZT, Ding WX. The end of RIPK1-RIPK3-MLKL-mediated necroptosis in acetaminophen-induced hepatotoxicity?. Hepatology 2016; 64 (01) 311-312
    PubMedSearch in Google Scholar
  • 117 Schneider AT, Gautheron J, Tacke F, Vucur M, Luedde T. Receptor interacting protein kinase 1 (RIPK1) in hepatocytes does not mediate murine acetaminophen toxicity. Hepatology 2016; 64 (01) 306-308
    PubMedSearch in Google Scholar
  • 118 Ramachandran A, McGill MR, Xie Y, Ni HM, Ding WX, Jaeschke H. Receptor interacting protein kinase 3 is a critical early mediator of acetaminophen-induced hepatocyte necrosis in mice. Hepatology 2013; 58 (06) 2099-2108
    PubMedSearch in Google Scholar
  • 119 Dara L, Johnson H, Suda J. et al. Receptor interacting protein kinase 1 mediates murine acetaminophen toxicity independent of the necrosome and not through necroptosis. Hepatology 2015; 62 (06) 1847-1857
    PubMedSearch in Google Scholar
  • 120 Lőrincz T, Jemnitz K, Kardon T, Mandl J, Szarka A. Ferroptosis is involved in acetaminophen induced cell death. Pathol Oncol Res 2015; 21 (04) 1115-1121
    PubMedSearch in Google Scholar
  • 121 Yamada N, Karasawa T, Kimura H. et al. Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure. Cell Death Dis 2020; 11 (02) 144
    PubMedSearch in Google Scholar
  • 122 Adelusi OB, Etemadi Y, Akakpo JY, Ramachandran A, Jaeschke H. Effect of ferroptosis inhibitors in a murine model of acetaminophen-induced liver injury. J Biochem Mol Toxicol 2024; 38 (08) e23791
    PubMedSearch in Google Scholar
  • 123 Knight TR, Fariss MW, Farhood A, Jaeschke H. Role of lipid peroxidation as a mechanism of liver injury after acetaminophen overdose in mice. Toxicol Sci 2003; 76 (01) 229-236
    PubMedSearch in Google Scholar
  • 124 Adelusi OB, Ramachandran A, Lemasters JJ. et al. The role of iron in lipid peroxidation and protein nitration during acetaminophen-induced liver injury in mice. Toxicol Appl Pharm 2022; 445: 116043
    PubMedSearch in Google Scholar
  • 125 Woolbright BL, Jaeschke H. Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure. J Hepatol 2017; 66 (04) 836-848
    PubMedSearch in Google Scholar
  • 126 Imaeda AB, Watanabe A, Sohail MA. et al. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J Clin Invest 2009; 119 (02) 305-314
    PubMedSearch in Google Scholar
  • 127 Williams CD, Antoine DJ, Shaw PJ. et al. Role of the Nalp3 inflammasome in acetaminophen-induced sterile inflammation and liver injury. Toxicol Appl Pharmacol 2011; 252 (03) 289-297
    PubMedSearch in Google Scholar
  • 128 Williams CD, Farhood A, Jaeschke H. Role of caspase-1 and interleukin-1beta in acetaminophen-induced hepatic inflammation and liver injury. Toxicol Appl Pharmacol 2010; 247 (03) 169-178
    PubMedSearch in Google Scholar
  • 129 Nguyen NT, Umbaugh DS, Smith S. et al. Dose-dependent pleiotropic role of neutrophils during acetaminophen-induced liver injury in male and female mice. Arch Toxicol 2023; 97 (05) 1397-1412
    PubMedSearch in Google Scholar
  • 130 Li Z, Wang H, Zhu J. et al. Inhibition of TWEAK/Tnfrsf12a axis protects against acute liver failure by suppressing RIPK1-dependent apoptosis. Cell Death Discov 2022; 8 (01) 328
    PubMedSearch in Google Scholar
  • 131 Ouyang SX, Zhu JH, Cao Q. et al. Gasdermin-E-dependent non-canonical pyroptosis promotes drug-induced liver failure by promoting CPS1 deISGylation and degradation. Adv Sci (Weinh) 2024; 11 (16) e2305715
    PubMedSearch in Google Scholar
  • 132 Chao X, Qian H, Wang S, Fulte S, Ding WX. Autophagy and liver cancer. Clin Mol Hepatol 2020; 26 (04) 606-617
    PubMedSearch in Google Scholar
  • 133 Ni HM, Bockus A, Boggess N, Jaeschke H, Ding WX. Activation of autophagy protects against acetaminophen-induced hepatotoxicity. Hepatology 2012; 55 (01) 222-232
    PubMedSearch in Google Scholar
  • 134 Ni HM, McGill MR, Chao X. et al. Removal of acetaminophen protein adducts by autophagy protects against acetaminophen-induced liver injury in mice. J Hepatol 2016; 65 (02) 354-362
    PubMedSearch in Google Scholar
  • 135 Wang H, Ni HM, Chao X. et al. Double deletion of PINK1 and Parkin impairs hepatic mitophagy and exacerbates acetaminophen-induced liver injury in mice. Redox Biol 2019; 22: 101148
    PubMedSearch in Google Scholar
  • 136 Williams JA, Ni HM, Haynes A. et al. Chronic deletion and acute knockdown of Parkin have differential responses to acetaminophen-induced mitophagy and liver injury in mice. J Biol Chem 2015; 290 (17) 10934-10946
    PubMedSearch in Google Scholar
  • 137 Li Y, Ni HM, Jaeschke H, Ding WX. Chlorpromazine protects against acetaminophen-induced liver injury in mice by modulating autophagy and c-Jun N-terminal kinase activation. Liver Res 2019; 3 (01) 65-74
    PubMedSearch in Google Scholar
  • 138 Chao X, Niu M, Wang S. et al. High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice. Acta Pharm Sin B 2024; 14 (01) 190-206
    PubMedSearch in Google Scholar
  • 139 Ni HM, Boggess N, McGill MR. et al. Liver-specific loss of Atg5 causes persistent activation of Nrf2 and protects against acetaminophen-induced liver injury. Toxicol Sci 2012; 127 (02) 438-450
    PubMedSearch in Google Scholar
  • 140 Rinella ME, Lazarus JV, Ratziu V. et al; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol 2023; 79 (06) 1542-1556
    CrossrefPubMedSearch in Google Scholar
  • 141 Rinella ME, Lazarus JV, Ratziu V. et al; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology 2023; 78 (06) 1966-1986
    CrossrefPubMedSearch in Google Scholar
  • 142 Thapaliya S, Wree A, Povero D. et al. Caspase 3 inactivation protects against hepatic cell death and ameliorates fibrogenesis in a diet-induced NASH model. Dig Dis Sci 2014; 59 (06) 1197-1206
    PubMedSearch in Google Scholar
  • 143 Feldstein AE, Canbay A, Angulo P. et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology 2003; 125 (02) 437-443
    PubMedSearch in Google Scholar
  • 144 Witek RP, Stone WC, Karaca FG. et al. Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis. Hepatology 2009; 50 (05) 1421-1430
    PubMedSearch in Google Scholar
  • 145 Zhao P, Sun X, Chaggan C. et al. An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis. Science 2020; 367 (6478) 652-660
    PubMedSearch in Google Scholar
  • 146 Szegezdi E, Logue SE, Gorman AM, Samali A. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 2006; 7 (09) 880-885
    PubMedSearch in Google Scholar
  • 147 Kim JY, Garcia-Carbonell R, Yamachika S. et al. ER stress drives lipogenesis and steatohepatitis via caspase-2 activation of S1P. Cell 2018; 175 (01) 133-145.e15
    CrossrefPubMedSearch in Google Scholar
  • 148 Harrison SA, Goodman Z, Jabbar A. et al. A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis. J Hepatol 2020; 72 (05) 816-827
    CrossrefPubMedSearch in Google Scholar
  • 149 Ni HM, McGill MR, Chao X, Woolbright BL, Jaeschke H, Ding WX. Caspase inhibition prevents tumor necrosis factor-α-induced apoptosis and promotes necrotic cell death in mouse hepatocytes in vivo and in vitro. Am J Pathol 2016; 186 (10) 2623-2636
    PubMedSearch in Google Scholar
  • 150 Roychowdhury S, McCullough RL, Sanz-Garcia C. et al. Receptor interacting protein 3 protects mice from high-fat diet-induced liver injury. Hepatology 2016; 64 (05) 1518-1533
    PubMedSearch in Google Scholar
  • 151 Wu X, Poulsen KL, Sanz-Garcia C. et al. MLKL-dependent signaling regulates autophagic flux in a murine model of non-alcohol-associated fatty liver and steatohepatitis. J Hepatol 2020; 73 (03) 616-627
    PubMedSearch in Google Scholar
  • 152 Gautheron J, Vucur M, Reisinger F. et al. A positive feedback loop between RIP3 and JNK controls non-alcoholic steatohepatitis. EMBO Mol Med 2014; 6 (08) 1062-1074
    PubMedSearch in Google Scholar
  • 153 Tao L, Yi Y, Chen Y. et al. RIP1 kinase activity promotes steatohepatitis through mediating cell death and inflammation in macrophages. Cell Death Differ 2021; 28 (04) 1418-1433
    PubMedSearch in Google Scholar
  • 154 Gautheron J, Vucur M, Schneider AT. et al. The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance. Nat Commun 2016; 7: 11869
    PubMedSearch in Google Scholar
  • 155 Corradini E, Buzzetti E, Dongiovanni P. et al. Ceruloplasmin gene variants are associated with hyperferritinemia and increased liver iron in patients with NAFLD. J Hepatol 2021; 75 (03) 506-513
    PubMedSearch in Google Scholar
  • 156 Li X, Wang TX, Huang X. et al. Targeting ferroptosis alleviates methionine-choline deficient (MCD)-diet induced NASH by suppressing liver lipotoxicity. Liver Int 2020; 40 (06) 1378-1394
    PubMedSearch in Google Scholar
  • 157 Tao L, Yang X, Ge C. et al. Integrative clinical and preclinical studies identify FerroTerminator1 as a potent therapeutic drug for MASH. Cell Metab 2024; 36 (10) 2190-2206.e5
    PubMedSearch in Google Scholar
  • 158 Loguercio C, De Girolamo V, de Sio I. et al. Non-alcoholic fatty liver disease in an area of southern Italy: main clinical, histological, and pathophysiological aspects. J Hepatol 2001; 35 (05) 568-574
    PubMedSearch in Google Scholar
  • 159 Chalasani N, Deeg MA, Crabb DW. Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2004; 99 (08) 1497-1502
    PubMedSearch in Google Scholar
  • 160 Qi J, Kim JW, Zhou ZX. et al. Ferroptosis affects the progression of nonalcoholic steatohepatitis via the modulation of lipid peroxidation mediated cell death in mice (vol 190, pg 68, 2020). Am J Pathol 2020; 190: 723
    PubMedSearch in Google Scholar
  • 161 Sumida Y, Yoneda M, Seko Y. et al; Japan Study Group of NAFLD (JSG-NAFLD). Role of vitamin E in the treatment of non-alcoholic steatohepatitis. Free Radic Biol Med 2021; 177: 391-403
    PubMedSearch in Google Scholar
  • 162 Duan J, Wang Z, Duan R. et al. Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice. Hepatology 2022; 75 (01) 140-153
    PubMedSearch in Google Scholar
  • 163 Shen J, Xie E, Shen S. et al. Essentiality of SLC7A11-mediated nonessential amino acids in MASLD. Sci Bull (Beijing) 2024; 69 (23) 3700-3716
    PubMedSearch in Google Scholar
  • 164 Sbodio JI, Snyder SH, Paul BD. Regulators of the transsulfuration pathway. Br J Pharmacol 2019; 176 (04) 583-593
    PubMedSearch in Google Scholar
  • 165 Xu B, Jiang M, Chu Y. et al. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice. J Hepatol 2018; 68 (04) 773-782
    PubMedSearch in Google Scholar
  • 166 Koh EH, Yoon JE, Ko MS. et al. Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis. Gut 2021; 70 (10) 1954-1964
    PubMedSearch in Google Scholar
  • 167 Gaul S, Leszczynska A, Alegre F. et al. Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis. J Hepatol 2021; 74 (01) 156-167
    PubMedSearch in Google Scholar
  • 168 Kaufman B, Kui L, Reca A. Cell-specific deletion of NLRP3 inflammasome identifies myeloid cells as key drivers of liver inflammation and fibrosis in murine steatohepatitis (vol 14, pg 751, 2022). Cell Mol Gastroenter 2024; 17: 319
    PubMedSearch in Google Scholar
  • 169 Babuta M, Morel C, de Carvalho Ribeiro M. et al. Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis. Gut 2024; 73 (11) 1854-1869
    PubMedSearch in Google Scholar
  • 170 Henao-Mejia J, Elinav E, Jin C. et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012; 482 (7384) 179-185
    PubMedSearch in Google Scholar
  • 171 Yang L, Li P, Fu S, Calay ES, Hotamisligil GS. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab 2010; 11 (06) 467-478
    PubMedSearch in Google Scholar
  • 172 Li Y, Chao X, Yang L. et al. Impaired fasting-induced adaptive lipid droplet biogenesis in liver-specific Atg5-deficient mouse liver is mediated by persistent nuclear factor-like 2 activation. Am J Pathol 2018; 188 (08) 1833-1846
    PubMedSearch in Google Scholar
  • 173 Ma D, Molusky MM, Song J. et al. Autophagy deficiency by hepatic FIP200 deletion uncouples steatosis from liver injury in NAFLD. Mol Endocrinol 2013; 27 (10) 1643-1654
    PubMedSearch in Google Scholar
  • 174 Takahashi SS, Sou YS, Saito T. et al. Loss of autophagy impairs physiological steatosis by accumulation of NCoR1. Life Sci Alliance 2019; 3 (01) 3
    PubMedSearch in Google Scholar
  • 175 Chao X, Wang S, Fulte S. et al. Hepatocytic p62 suppresses ductular reaction and tumorigenesis in mouse livers with mTORC1 activation and defective autophagy. J Hepatol 2022; 76 (03) 639-651
    PubMedSearch in Google Scholar
  • 176 Nguyen TB, Louie SM, Daniele JR. et al. DGAT1-dependent lipid droplet biogenesis protects mitochondrial function during starvation-induced autophagy. Dev Cell 2017; 42 (01) 9-21.e5
    PubMedSearch in Google Scholar
  • 177 Baselli GA, Jamialahmadi O, Pelusi S. et al; EPIDEMIC Study Investigators. Rare ATG7 genetic variants predispose patients to severe fatty liver disease. J Hepatol 2022; 77 (03) 596-606
    PubMedSearch in Google Scholar
  • 178 Ding WX, Ni HM, Waguri S, Komatsu M. Lack of hepatic autophagy promotes severity of liver injury but not steatosis. J Hepatol 2022; 77 (05) 1458-1459
    PubMedSearch in Google Scholar
  • 179 Mackowiak B, Fu Y, Maccioni L, Gao B. Alcohol-associated liver disease. J Clin Invest 2024; 134 (03) 134
    CrossrefPubMedSearch in Google Scholar
  • 180 Liangpunsakul S, Haber P, McCaughan GW. Alcoholic liver disease in Asia, Europe, and North America. Gastroenterology 2016; 150 (08) 1786-1797
    CrossrefPubMedSearch in Google Scholar
  • 181 Nagy LE, Ding WX, Cresci G, Saikia P, Shah VH. Linking pathogenic mechanisms of alcoholic liver disease with clinical phenotypes. Gastroenterology 2016; 150 (08) 1756-1768
    PubMedSearch in Google Scholar
  • 182 Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 2011; 141 (05) 1572-1585
    CrossrefPubMedSearch in Google Scholar
  • 183 Williams JA, Manley S, Ding WX. New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases. World J Gastroenterol 2014; 20 (36) 12908-12933
    PubMedSearch in Google Scholar
  • 184 Gao H, Jiang Y, Zeng G. et al. Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease. eGastroenterology 2024; 2 (04) 2
    PubMedSearch in Google Scholar
  • 185 Lambert JC, Zhou Z, Kang YJ. Suppression of Fas-mediated signaling pathway is involved in zinc inhibition of ethanol-induced liver apoptosis. Exp Biol Med (Maywood) 2003; 228 (04) 406-412
    PubMedSearch in Google Scholar
  • 186 Hartmann P, Seebauer CT, Schnabl B. Alcoholic liver disease: the gut microbiome and liver cross talk. Alcohol Clin Exp Res 2015; 39 (05) 763-775
    CrossrefPubMedSearch in Google Scholar
  • 187 Roychowdhury S, Chiang DJ, Mandal P. et al. Inhibition of apoptosis protects mice from ethanol-mediated acceleration of early markers of CCl4 -induced fibrosis but not steatosis or inflammation. Alcohol Clin Exp Res 2012; 36 (07) 1139-1147
    PubMedSearch in Google Scholar
  • 188 Hao F, Cubero FJ, Ramadori P. et al. Inhibition of Caspase-8 does not protect from alcohol-induced liver apoptosis but alleviates alcoholic hepatic steatosis in mice. Cell Death Dis 2017; 8 (10) e3152
    CrossrefPubMedSearch in Google Scholar
  • 189 He L, Sehrawat TS, Verma VK. et al. XIAP knockdown in alcohol-associated liver disease models exhibits divergent in vitro and in vivo phenotypes owing to a potential zonal inhibitory role of SMAC. Front Physiol 2021; 12: 664222
    PubMedSearch in Google Scholar
  • 190 Wang S, Ni HM, Dorko K. et al. Increased hepatic receptor interacting protein kinase 3 expression due to impaired proteasomal functions contributes to alcohol-induced steatosis and liver injury. Oncotarget 2016; 7 (14) 17681-17698
    PubMedSearch in Google Scholar
  • 191 Miyata T, Wu X, Fan X. et al. Differential role of MLKL in alcohol-associated and non-alcohol-associated fatty liver diseases in mice and humans. JCI Insight 2022; 7 (23) 7
    CrossrefPubMedSearch in Google Scholar
  • 192 Wu X, Fan X, McMullen MR. et al. Macrophage-derived MLKL in alcohol-associated liver disease: regulation of phagocytosis. Hepatology 2023; 77 (03) 902-919
    CrossrefPubMedSearch in Google Scholar
  • 193 Kohgo Y, Ohtake T, Ikuta K, Suzuki Y, Torimoto Y, Kato J. Dysregulation of systemic iron metabolism in alcoholic liver diseases. J Gastroenterol Hepatol 2008; 23 (Suppl. 01) S78-S81
    PubMedSearch in Google Scholar
  • 194 Yang C, Yang Y, Hu X. et al. Loss of GCN5L1 exacerbates damage in alcoholic liver disease through ferroptosis activation. Liver Int 2024; 44 (08) 1924-1936
    PubMedSearch in Google Scholar
  • 195 You Y, Liu C, Liu T. et al. FNDC3B protects steatosis and ferroptosis via the AMPK pathway in alcoholic fatty liver disease. Free Radic Biol Med 2022; 193 (Pt 2): 808-819
    CrossrefPubMedSearch in Google Scholar
  • 196 Ohtake T, Saito H, Hosoki Y. et al. Hepcidin is down-regulated in alcohol loading. Alcohol Clin Exp Res 2007; 31 (01) S2-S8
    PubMedSearch in Google Scholar
  • 197 Suzuki Y, Saito H, Suzuki M. et al. Up-regulation of transferrin receptor expression in hepatocytes by habitual alcohol drinking is implicated in hepatic iron overload in alcoholic liver disease. Alcohol Clin Exp Res 2002; 26 (08) 26S-31S
    PubMedSearch in Google Scholar
  • 198 Scott I, Wang L, Wu K, Thapa D, Sack MN. GCN5L1/BLOS1 links acetylation, organelle remodeling, and metabolism. Trends Cell Biol 2018; 28 (05) 346-355
    PubMedSearch in Google Scholar
  • 199 Hu X, Jogasuria A, Wang J. et al. MitoNEET deficiency alleviates experimental alcoholic steatohepatitis in mice by stimulating endocrine adiponectin-Fgf15 axis. J Biol Chem 2016; 291 (43) 22482-22495
    PubMedSearch in Google Scholar
  • 200 Petrasek J, Bala S, Csak T. et al. IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice. J Clin Invest 2012; 122 (10) 3476-3489
    PubMedSearch in Google Scholar
  • 201 Khanova E, Wu R, Wang W. et al. Pyroptosis by caspase11/4-gasdermin-D pathway in alcoholic hepatitis in mice and patients. Hepatology 2018; 67 (05) 1737-1753
    PubMedSearch in Google Scholar
  • 202 Chao X, Williams SN, Ding WX. Role of mechanistic target of rapamycin in autophagy and alcohol-associated liver disease. Am J Physiol Cell Physiol 2022; 323 (04) C1100-C1111
    PubMedSearch in Google Scholar
  • 203 Ding WX, Li M, Chen X. et al. Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice. Gastroenterology 2010; 139 (05) 1740-1752
    PubMedSearch in Google Scholar
  • 204 Ni HM, Du K, You M, Ding WX. Critical role of FoxO3a in alcohol-induced autophagy and hepatotoxicity. Am J Pathol 2013; 183 (06) 1815-1825
    CrossrefPubMedSearch in Google Scholar
  • 205 Samuvel DJ, Li L, Krishnasamy Y. et al. Mitochondrial depolarization after acute ethanol treatment drives mitophagy in living mice. Autophagy 2022; 18 (11) 2671-2685
    PubMedSearch in Google Scholar
  • 206 Thomes PG, Trambly CS, Fox HS, Tuma DJ, Donohue Jr TM. Acute and chronic ethanol administration differentially modulate hepatic autophagy and transcription factor EB. Alcohol Clin Exp Res 2015; 39 (12) 2354-2363
    CrossrefPubMedSearch in Google Scholar
  • 207 Chao X, Wang S, Zhao K. et al. Impaired TFEB-mediated lysosome biogenesis and autophagy promote chronic ethanol-induced liver injury and steatosis in mice. Gastroenterology 2018; 155 (03) 865-879.e12
    PubMedSearch in Google Scholar
  • 208 Chao X, Ni HM, Ding WX. Insufficient autophagy: a novel autophagic flux scenario uncovered by impaired liver TFEB-mediated lysosomal biogenesis from chronic alcohol-drinking mice. Autophagy 2018; 14 (09) 1646-1648
    PubMedSearch in Google Scholar
  • 209 Ma XW, Chen A, Melo L. et al. Loss of hepatic DRP1 exacerbates alcoholic hepatitis by inducing megamitochondria and mitochondrial maladaptation. Hepatology 2023; 77 (01) 159-175
    CrossrefPubMedSearch in Google Scholar