The role of the mitochondria-inflammasome pathway in the progression of chronic liver disease

WU Huan; WU Long; ZHANG Baofang

doi:10.16766/j.cnki.issn.1674-4152.003972

Volume 23 Issue 4

Apr. 2025

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Article Navigation > Chinese Journal of General Practice > 2025 > 23(4): 651-655

WU Huan, WU Long, ZHANG Baofang. The role of the mitochondria-inflammasome pathway in the progression of chronic liver disease[J]. Chinese Journal of General Practice, 2025, 23(4): 651-655. doi: 10.16766/j.cnki.issn.1674-4152.003972

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WU Huan, WU Long, ZHANG Baofang. The role of the mitochondria-inflammasome pathway in the progression of chronic liver disease[J]. Chinese Journal of General Practice, 2025, 23(4): 651-655. doi: 10.16766/j.cnki.issn.1674-4152.003972

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The role of the mitochondria-inflammasome pathway in the progression of chronic liver disease

doi: 10.16766/j.cnki.issn.1674-4152.003972

WU Huan¹
, WU Long²
, ZHANG Baofang^{1
,
,}

1.
Department of Infectious Diseases, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, China

Funds:

gzwkj2024-10

黔科合基础-ZK[2024]一般210

gzwkj2023-042

Received Date: 2024-03-21
Available Online: 2025-06-30

Abstract

Abstract

Chronic liver disease is a serious global health concern, with increasing incidence and mortality rates. Mitochondrial dysfunction and activation of the inflammasome pathway play key roles in the progression of chronic liver disease. As the energy center of cells, mitochondria are involved not only in energy metabolism but also in apoptosis, oxidative stress, and inflammation. The inflammasome, an intracellular multiprotein complex, is essential for the cell' s response to pathogens and cellular stress. Recent studies have increasingly linked mitochondria and inflammasome activation, revealing that mitochondria play an important role in inflammasome activation. Damaged mitochondria release signaling molecules that promote the formation and activation of inflammasome, triggering the release of inflammatory cytokines such as IL-1β, IL-18, and TNF-α. Additionally, mitochondria-related proteins directly participate in the assembly and activation of inflammasome. Current researches have shed light on the relationship between mitochondria and inflammasomes in chronic liver disease. In this review, we aim to elaborate on the structure, activation signal pathways, regulatory mechanisms, and their relationship with chronic liver diseases. These insights may offer new directions and targets for the treatment of chronic liver diseases.
- Mitochondria,
- Inflammasome,
- Chronic liver disease

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References(43)

References

[1]	MA X W, MCKEEN T, ZHANG J H, et al. Role and mechanisms of mitophagy in liver diseases[J]. Cells, 2020, 9(4): 837. DOI: 10.3390/cells9040837.
[2]	WANG J X, SUN Z W, XIE J R, et al. Inflammasome and pyroptosis in autoimmune liver diseases[J]. Front Immunol, 2023, 14: 1150879. DOI: 10.3389/fimmu.2023.1150879.
[3]	BI Y G, LIU S L, QIN X, et al. FUNDC1 interacts with GPx4 to govern hepatic ferroptosis and fibrotic injury through a mitophagy-dependent manner[J]. J Adv Res, 2024, 55: 45-60. doi: 10.1016/j.jare.2023.02.012
[4]	WU N N, WANG L F, WANG L, et al. Site-specific ubiquitination of VDAC1 restricts its oligomerization and mitochondrial DNA release in liver fibrosis[J]. Exp Mol Med, 2023, 55(1): 269-280. doi: 10.1038/s12276-022-00923-9
[5]	AKBAL A, DERNST A, LOVOTTI M, et al. How location and cellular signaling combine to activate the NLRP3 inflammasome[J]. Cell Mol Immunol, 2022, 19(11): 1201-1214. doi: 10.1038/s41423-022-00922-w
[6]	SZABO G, PETRASEK J. Inflammasome activation and function in liver disease[J]. Nat Rev Gastroenterol Hepatol, 2015, 12(7): 387-400. doi: 10.1038/nrgastro.2015.94
[7]	QU C B, ZHANG S S, LI Y, et al. Mitochondria in the biology, pathogenesis, and treatment of hepatitis virus infections[J]. Rev Med Virol, 2019, 29(5): e2075. DOI: 10.1002/rmv.2075.
[8]	XIE W H, DING J, XIE X X, et al. Hepatitis B virus X protein promotes liver cell pyroptosis under oxidative stress through NLRP3 inflammasome activation[J]. Inflamm Res, 2020, 69(7): 683-696. doi: 10.1007/s00011-020-01351-z
[9]	YOUNOSSI Z M. Non-alcoholic fatty liver disease: a global public health perspective[J]. J Hepatol, 2019, 70(3): 531-544. doi: 10.1016/j.jhep.2018.10.033
[10]	ASRANI S K, DEVARBHAVI H, EATON J, et al. Burden of liver diseases in the world[J]. J Hepatol, 2019, 70(1): 151-171. doi: 10.1016/j.jhep.2018.09.014
[11]	GONG F, GAO L, DING T. IDH2 protects against nonalcoholic steatohepatitis by alleviating dyslipidemia regulated by oxidative stress[J]. Biochem Biophys Res Commun, 2019, 514(3): 593-600. doi: 10.1016/j.bbrc.2019.04.069
[12]	ACÍN-PÉREZ R, IBORRA S, MARTÍ-MATEOS Y, et al. Fgr kinase is required for proinflammatory macrophage activation during diet-induced obesity[J]. Nat Metab, 2020, 2(9): 974-988. doi: 10.1038/s42255-020-00273-8
[13]	ZHONG Z Y, LIANG S, SANCHEZ-LOPEZ E, et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation[J]. Nature, 2018, 560(7717): 198-203. doi: 10.1038/s41586-018-0372-z
[14]	ZHANG H Z, SHI H M, XIE W, et al. Subacute ruminal acidosis induces pyroptosis via the mitophagy-mediated NLRP3 inflammasome activation in the livers of dairy cows fed a high-grain diet[J]. J Dairy Sci, 2024, 107(6): 4092-4107. doi: 10.3168/jds.2023-23718
[15]	ZHANG N P, LIU X J, XIE L, et al. Impaired mitophagy triggers NLRP3 inflammasome activation during the progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis[J]. Lab Invest, 2019, 99(6): 749-763. doi: 10.1038/s41374-018-0177-6
[16]	CHEN Y H, MA K F. NLRC4 inflammasome activation regulated by TNF-α promotes inflammatory responses in nonalcoholic fatty liver disease[J]. Biochem Biophys Res Commun, 2019, 511(3): 524-530. doi: 10.1016/j.bbrc.2019.02.099
[17]	ZHANG J L, ZHAO Y J, WANG S H, et al. CREBH alleviates mitochondrial oxidative stress through SIRT3 mediating deacetylation of MnSOD and suppression of Nlrp3 inflammasome in NASH[J]. Free Radic Biol Med, 2022, 190: 28-41. doi: 10.1016/j.freeradbiomed.2022.07.018
[18]	TIAN C, MIN X W, ZHAO Y X, et al. MRG15 aggravates non-alcoholic steatohepatitis progression by regulating the mitochondrial proteolytic degradation of TUFM[J]. J Hepatol, 2022, 77(6): 1491-1503. doi: 10.1016/j.jhep.2022.07.017
[19]	JIN K P, SHI Y Z, ZHANG H T, et al. A TNFα/Miz1-positive feedback loop inhibits mitophagy in hepatocytes and propagates non-alcoholic steatohepatitis[J]. J Hepatol, 2023, 79(2): 403-416. doi: 10.1016/j.jhep.2023.03.039
[20]	YU X Y, HAO M, LIU Y, et al. Liraglutide ameliorates non-alcoholic steatohepatitis by inhibiting NLRP3 inflammasome and pyroptosis activation via mitophagy[J]. Eur J Pharmacol, 2019, 864: 172715. DOI: 10.1016/j.ejphar.2019.172715.
[21]	MENG Z Q, GAO M, WANG C Y, et al. Apigenin alleviated high-fat-diet-induced hepatic pyroptosis by mitophagy-ROS-CTSB-NLRP3 pathway in mice and AML12 cells[J]. J Agric Food Chem, 2023, 71(18): 7032-7045. doi: 10.1021/acs.jafc.2c07581
[22]	TORRES S, SEGALÉS P, GARCÍA-RUIZ C, et al. Mitochondria and the NLRP3 inflammasome in alcoholic and nonalcoholic steatohepatitis[J]. Cells, 2022, 11(9): 1475. DOI: 10.3390/cells11091475.
[23]	KAI J, YANG X, WANG Z M, et al. Oroxylin a promotes PGC-1alpha/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease[J]. Free Radic Biol Med, 2020, 153: 89-102. doi: 10.1016/j.freeradbiomed.2020.03.031
[24]	GAO Y, XU G, MA L, et al. Icariside Ⅰ specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity[J]. Cell Commun Signal, 2021, 19(1): 13. DOI: 10.1186/s12964-020-00647-1.
[25]	LIN L, CHEN Y Y, LI Q, et al. Isoxanthohumol, a component of Sophora flavescens, promotes the activation of the NLRP3 inflammasome and induces idiosyncratic hepatotoxicity[J]. J Ethnopharmacol, 2022, 285: 114796. DOI: 10.1016/j.jep.2021.114796.
[26]	SHI W, LIU T T, YANG H J, et al. Isomaculosidine facilitates NLRP3 inflammasome activation by promoting mitochondrial reactive oxygen species production and causes idiosyncratic liver injury[J]. J Ethnopharmacol, 2024, 319(Pt 1): 117063. DOI: 10.1016/j.jep.2023.117063.
[27]	WANG Y, ZHAO Y, WANG Z C, et al. Peroxiredoxin 3 inhibits acetaminophen-induced liver pyroptosis through the regulation of mitochondrial ROS[J]. Front Immunol, 2021, 12: 652782. DOI: 10.3389/fimmu.2021.652782.
[28]	WANG Q, JIA F B, GUO C, et al. PINK1/Parkin-mediated mitophagy as a protective mechanism against AFB(1)-induced liver injury in mice[J]. Food Chem Toxicol, 2022, 164: 113043. DOI: 10.1016/j.fct.2022.113043.
[29]	SHAN S L, SHEN Z Y, ZHANG C Q, et al. Mitophagy protects against acetaminophen-induced acute liver injury in mice through inhibiting NLRP3 inflammasome activation[J]. Biochem Pharmacol, 2019, 169: 113643. DOI: 10.1016/j.bcp.2019.113643.
[30]	ZHU D J, ZHONG J, GONG X F, et al. Augmenter of liver regeneration reduces mitochondria-derived ROS and NLRP3 inflammasome activation through PINK1/Parkin-mediated mitophagy in ischemia-reperfusion-induced renal tubular injury[J]. Apoptosis, 2023, 28(3-4): 335-347. doi: 10.1007/s10495-022-01794-1
[31]	ZHANG Q, HU J P, MAO A K, et al. Ginsenoside RB1 alleviated concanavalin A-induced hepatocyte pyroptosis by activating mitophagy[J]. Food Funct, 2023, 14(8): 3793-3803. doi: 10.1039/D2FO03130B
[32]	CHANG H F, YANG F, BAI H, et al. Molybdenum and/or cadmium induce NLRP3 inflammasome production by causing mitochondria-associated endoplasmic reticulum membrane dysfunction in sheep hepatocytes[J]. Chem Biol Interact, 2023, 382: 110617. DOI: 10.1016/j.cbi.2023.110617.
[33]	LIU Z N, WANG X F, LI L, et al. Hydrogen sulfide protects against paraquat-induced acute liver injury in rats by regulating oxidative stress, mitochondrial function, and inflammation[J]. Oxid Med Cell Longev, 2020, 2020: 6325378. DOI: 10.1155/2020/6325378.
[34]	ZHAO Y, WANG Z C, FENG D C, et al. P66shc contributes to liver fibrosis through the regulation of mitochondrial reactive oxygen species[J]. Theranostics, 2019, 9(5): 1510-1522. doi: 10.7150/thno.29620
[35]	CHEON S Y, KIM M Y, KIM J, et al. Hyperammonemia induces microglial NLRP3 inflammasome activation via mitochondrial oxidative stress in hepatic encephalopathy[J]. Biomed J, 2023, 46(5): 100593. DOI: 10.1016/j.bj.2023.04.001.
[36]	LI H L, ZHANG R T, HU Y Y, et al. Axitinib attenuates the progression of liver fibrosis by restoring mitochondrial function[J]. Int Immunopharmacol, 2023, 122: 110555. DOI: 10.1016/j.intimp.2023.110555.
[37]	WU Y, HAO C, LIU X F, et al. MitoQ protects against liver injury induced by severe burn plus delayed resuscitation by suppressing the mtDNA-NLRP3 axis[J]. Int Immunopharmacol, 2020, 80: 106189. DOI: 10.1016/j.intimp.2020.106189.
[38]	ZHAO H J, ZHANG Y M, ZHANG Y T, et al. The role of NLRP3 inflammasome in hepatocellular carcinoma[J]. Front Pharmacol, 2023, 14: 1150325. DOI: 10.3389/fphar.2023.1150325.
[39]	耿西林, 张颖, 李浩, 等. 线粒体动力相关蛋白DRP1对肝癌细胞糖代谢的调控作用研究[J]. 中华全科医学, 2022, 20(1): 35-38. doi: 10.16766/j.cnki.issn.1674-4152.002270 GENG X L, ZHANG Y, LI H, et al. Regulation of mitochondrial dynamic-related protein 1 on glucose metabolism in liver cancer cells[J]. Chinese Journal of General Practice, 2022, 20(1): 35-38. doi: 10.16766/j.cnki.issn.1674-4152.002270
[40]	LI W H, LI Y J, SIRAJ S, et al. FUN14 domain-containing 1-mediated mitophagy suppresses hepatocarcinogenesis by inhibition of inflammasome activation in mice[J]. Hepatology, 2019, 69(2): 604-621. doi: 10.1002/hep.30191
[41]	ZHENG P P, XIAO W L, ZHANG J P, et al. The role of AIM2 in human hepatocellular carcinoma and its clinical significance[J]. Pathol Res Pract, 2023, 245: 154454. DOI: 10.1016/j.prp.2023.154454.
[42]	SHI X L, WANG L, REN L F, et al. Dihydroartemisinin, an antimalarial drug, induces absent in melanoma 2 inflammasome activation and autophagy in human hepatocellular carcinoma HepG2215 cells[J]. Phytother Res, 2019, 33(5): 1413-1425. doi: 10.1002/ptr.6332
[43]	LIU Y, GUO Z W, LI J, et al. Insight into the regulation of NLRP3 inflammasome activation by mitochondria in liver injury and the protective role of natural products[J]. Biomed Pharmacother, 2022, 156: 113968. DOI: 10.1016/j.biopha.2022.113968.

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The role of the mitochondria-inflammasome pathway in the progression of chronic liver disease

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