中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 8
Aug.  2022
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(8): 1931-1936

Association between glycolysis and mitochondrial dysfunction and its potential value in liver diseases

DOI: 10.3969/j.issn.1001-5256.2022.08.042
  • 1.

    Graduate School of Guangxi University of Chinese Medicine, Nanning 530200, China

  • 2.

    Second Ward of Hepatology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China

Research funding:

National Natural Science Foundation of China (81960841);

National Science and Technology Major Project (2018ZX10725505-001-011);

Guangxi Science and Technology Project (2020GXNSFAA297098);

Guangxi University of Traditional Chinese Medicine Graduate Innovation Project (YCXJ2021034)

More Information
  • Corresponding author: LONG Fuli, longfuli005@163.com(ORCID: 0000-0003-1196-2697)
  • Received Date: 2022-04-18
  • Accepted Date: 2022-05-29
  • Published Date: 2022-08-20
    Abstract
  • Glycolysis plays an important role in the development and progression of liver diseases and shows varying degrees of enhancement in different liver diseases, and it is closely associated with mitochondrial dysfunction (oxidative phosphorylation deficiency and reactive oxygen species production), which helps to fill energy production deficiency caused by impaired oxidative phosphorylation. Therefore, it might be possible to search for potential new therapies for liver diseases through targeted regulation of the key factors in aerobic glycolysis, such as hexokinase 2, pyruvate kinase M2, and other regulatory pathways. From the perspective of the association between glycolysis and liver diseases, this article elaborates on the therapeutic significance and potential value of glycolysis in liver diseases, in order to provide new ideas for the diagnosis and treatment of liver diseases.

     

    • FullText(HTML)
  • loading
    • References(45)
  • [1]
    AUGER C, ALHASAWI A, CONTAVADOO M, et al. Dysfunctional mitochondrial bioenergetics and the pathogenesis of hepatic disorders[J]. Front Cell Dev Biol, 2015, 3: 40. DOI: 10.3389/fcell.2015.00040.
    [2]
    WALLACE DC, FAN W, PROCACCIO V. Mitochondrial energetics and therapeutics[J]. Annu Rev Pathol, 2010, 5: 297-348. DOI: 10.1146/annurev.pathol.4.110807.092314.
    [3]
    NISHIKAWA T, BELLANCE N, DAMM A, et al. A switch in the source of ATP production and a loss in capacity to perform glycolysis are hallmarks of hepatocyte failure in advance liver disease[J]. J Hepatol, 2014, 60(6): 1203-1211. DOI: 10.1016/j.jhep.2014.02.014.
    [4]
    GO Y, JEONG JY, JEOUNG NH, et al. Inhibition of pyruvate dehydrogenase kinase 2 protects against hepatic steatosis through modulation of tricarboxylic acid cycle anaplerosis and ketogenesis[J]. Diabetes, 2016, 65(10): 2876-2887. DOI: 10.2337/db16-0223.
    [5]
    ZHANG M, ZHAO Y, LI Z, et al. Pyruvate dehydrogenase kinase 4 mediates lipogenesis and contributes to the pathogenesis of nonalcoholic steatohepatitis[J]. Biochem Biophys Res Commun, 2018, 495(1): 582-586. DOI: 10.1016/j.bbrc.2017.11.054.
    [6]
    SHIRAI T, NAZAREWICZ RR, WALLIS BB, et al. The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease[J]. J Exp Med, 2016, 213(3): 337-354. DOI: 10.1084/jem.20150900.
    [7]
    MIDDLETON P, VERGIS N. Mitochondrial dysfunction and liver disease: role, relevance, and potential for therapeutic modulation[J]. Therap Adv Gastroenterol, 2021, 14: 17562848211031394. DOI: 10.1177/17562848211031394.
    [8]
    GABBIA D, CANNELLA L, DE MARTIN S. The role of oxidative stress in NAFLD-NASH-HCC transition-focus on NADPH oxidases[J]. Biomedicines, 2021, 9(6): 687. DOI: 10.3390/biomedicines9060687.
    [9]
    LEE N, CARELLA MA, PAPA S, et al. High expression of glycolytic genes in cirrhosis correlates with the risk of developing liver cancer[J]. Front Cell Dev Biol, 2018, 6: 138. DOI: 10.3389/fcell.2018.00138.
    [10]
    LI S, LI J, DAI W, et al. Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death[J]. Br J Cancer, 2017, 117(10): 1518-1528. DOI: 10.1038/bjc.2017.323.
    [11]
    YE JH, CHAO J, CHANG ML, et al. Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation[J]. Sci Rep, 2016, 6: 33102. DOI: 10.1038/srep33102.
    [12]
    SHANG RZ, QU SB, WANG DS. Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects[J]. World J Gastroenterol, 2016, 22(45): 9933-9943. DOI: 10.3748/wjg.v22.i45.9933.
    [13]
    LUNT SY, VANDER HEIDEN MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation[J]. Annu Rev Cell Dev Biol, 2011, 27: 441-464. DOI: 10.1146/annurev-cellbio-092910-154237.
    [14]
    SCIACOVELLI M, GAUDE E, HILVO M, et al. The metabolic alterations of cancer cells[J]. Methods Enzymol, 2014, 542: 1-23. DOI: 10.1016/B978-0-12-416618-9.00001-7.
    [15]
    LIU J, JIANG S, ZHAO Y, et al. Geranylgeranyl diphosphate synthase (GGPPS) regulates non-alcoholic fatty liver disease (NAFLD)-fibrosis progression by determining hepatic glucose/fatty acid preference under high-fat diet conditions[J]. J Pathol, 2018, 246(3): 277-288. DOI: 10.1002/path.5131.
    [16]
    KORS L, RAMPANELLI E, STOKMAN G, et al. Deletion of NLRX1 increases fatty acid metabolism and prevents diet-induced hepatic steatosis and metabolic syndrome[J]. Biochim Biophys Acta Mol Basis Dis, 2018, 1864(5 Pt A): 1883-1895. DOI: 10.1016/j.bbadis.2018.03.003.
    [17]
    SHANNON CE, RAGAVAN M, PALAVICINI JP, et al. Insulin resistance is mechanistically linked to hepatic mitochondrial remodeling in non-alcoholic fatty liver disease[J]. Mol Metab, 2021, 45: 101154. DOI: 10.1016/j.molmet.2020.101154.
    [18]
    WANG T, CHEN K, YAO W, et al. Acetylation of lactate dehydrogenase B drives NAFLD progression by impairing lactate clearance[J]. J Hepatol, 2021, 74(5): 1038-1052. DOI: 10.1016/j.jhep.2020.11.028.
    [19]
    SHIMADA K, CROTHER TR, KARLIN J, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis[J]. Immunity, 2012, 36(3): 401-414. DOI: 10.1016/j.immuni.2012.01.009.
    [20]
    XU F, GUO M, HUANG W, et al. Annexin A5 regulates hepatic macrophage polarization via directly targeting PKM2 and ameliorates NASH[J]. Redox Biol, 2020, 36: 101634. DOI: 10.1016/j.redox.2020.101634.
    [21]
    SUN M, KISSELEVA T. Reversibility of liver fibrosis[J]. Clin Res Hepatol Gastroenterol, 2015, 39(Suppl 1): S60-S63. DOI: 10.1016/j.clinre.2015.06.015.
    [22]
    WANG F, JIA Y, LI M, et al. Blockade of glycolysis-dependent contraction by oroxylin a via inhibition of lactate dehydrogenase-a in hepatic stellate cells[J]. Cell Commun Signal, 2019, 17(1): 11. DOI: 10.1186/s12964-019-0324-8.
    [23]
    WAN L, XIA T, DU Y, et al. Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells[J]. FASEB J, 2019, 33(7): 8530-8542. DOI: 10.1096/fj.201802675R.
    [24]
    HUANG T, LI YQ, ZHOU MY, et al. Focal adhesion kinase-related non-kinase ameliorates liver fibrosis by inhibiting aerobic glycolysis via the FAK/Ras/c-myc/ENO1 pathway[J]. World J Gastroenterol, 2022, 28(1): 123-139. DOI: 10.3748/wjg.v28.i1.123.
    [25]
    RAO J, WANG H, NI M, et al. FSTL1 promotes liver fibrosis by reprogramming macrophage function through modulating the intracellular function of PKM2[J]. Gut, 2022. DOI: 10.1136/gutjnl-2021-325150.[Online ahead of print]
    [26]
    ZHENG D, JIANG Y, QU C, et al. Pyruvate kinase M2 tetramerization protects against hepatic stellate cell activation and liver fibrosis[J]. Am J Pathol, 2020, 190(11): 2267-2281. DOI: 10.1016/j.ajpath.2020.08.002.
    [27]
    ZHOU MY, CHENG ML, HUANG T, et al. Transforming growth factor beta-1 upregulates glucose transporter 1 and glycolysis through canonical and noncanonical pathways in hepatic stellate cells[J]. World J Gastroenterol, 2021, 27(40): 6908-6926. DOI: 10.3748/wjg.v27.i40.6908.
    [28]
    BAN D, HUA S, ZHANG W, et al. Costunolide reduces glycolysis-associated activation of hepatic stellate cells via inhibition of hexokinase-2[J]. Cell Mol Biol Lett, 2019, 24: 52. DOI: 10.1186/s11658-019-0179-4.
    [29]
    MATHUPALA SP, KO YH, PEDERSEN PL. Hexokinase-2 bound to mitochondria: cancer's stygian link to the "Warburg Effect" and a pivotal target for effective therapy[J]. Semin Cancer Biol, 2009, 19(1): 17-24. DOI: 10.1016/j.semcancer.2008.11.006.
    [30]
    VAUPEL P, SCHMIDBERGER H, MAYER A. The Warburg effect: essential part of metabolic reprogramming and central contributor to cancer progression[J]. Int J Radiat Biol, 2019, 95(7): 912-919. DOI: 10.1080/09553002.2019.1589653.
    [31]
    DEWAAL D, NOGUEIRA V, TERRY AR, et al. Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin[J]. Nat Commun, 2018, 9(1): 446. DOI: 10.1038/s41467-017-02733-4.
    [32]
    MATHUPALA SP, KO YH, PEDERSEN PL. Hexokinase-2 bound to mitochondria: cancer's stygian link to the "Warburg Effect" and a pivotal target for effective therapy[J]. Semin Cancer Biol, 2009, 19(1): 17-24. DOI: 10.1016/j.semcancer.2008.11.006.
    [33]
    KANAI S, SHIMADA T, NARITA T, et al. Phosphofructokinase-1 subunit composition and activity in the skeletal muscle, liver, and brain of dogs[J]. J Vet Med Sci, 2019, 81(5): 712-716. DOI: 10.1292/jvms.19-0049.
    [34]
    BARTRONS R, RODRÍGUEZ-GARCÍA A, SIMON-MOLAS H, et al. The potential utility of PFKFB3 as a therapeutic target[J]. Expert Opin Ther Targets, 2018, 22(8): 659-674. DOI: 10.1080/14728222.2018.1498082.
    [35]
    LI S, DAI W, MO W, et al. By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma[J]. Int J Cancer, 2017, 141(12): 2571-2584. DOI: 10.1002/ijc.31022.
    [36]
    van NIEKERK G, ENGELBRECHT AM. Role of PKM2 in directing the metabolic fate of glucose in cancer: a potential therapeutic target[J]. Cell Oncol (Dordr), 2018, 41(4): 343-351. DOI: 10.1007/s13402-018-0383-7.
    [37]
    AZOITEI N, BECHER A, STEINESTEL K, et al. PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation[J]. Mol Cancer, 2016, 15: 3. DOI: 10.1186/s12943-015-0490-2.
    [38]
    LUO W, HU H, CHANG R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1[J]. Cell, 2011, 145(5): 732-744. DOI: 10.1016/j.cell.2011.03.054.
    [39]
    WONG N, OJO D, YAN J, et al. PKM2 contributes to cancer metabolism[J]. Cancer Lett, 2015, 356(2 Pt A): 184-191. DOI: 10.1016/j.canlet.2014.01.031.
    [40]
    FENG J, WU L, JI J, et al. PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma[J]. J Exp Clin Cancer Res, 2019, 38(1): 204. DOI: 10.1186/s13046-019-1194-z.
    [41]
    LIU B, JIN J, ZHANG Z, et al. Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2-AMPK-PGC1α signaling pathway[J]. Biochem Cell Biol, 2019, 97(4): 397-405. DOI: 10.1139/bcb-2018-0310.
    [42]
    LING Y, YAN GJ, FENG F, et al. Association between cholesterol and liver regeneration and its significance and potential value in clinical treatment of liver failure[J]. J Clin Hepatol, 2022, 38(3): 708-713. DOI: 10.3969/j.issn.1001-5256.2022.03.044.

    林镛, 颜耿杰, 冯逢, 等. 胆固醇与肝再生关系及其在肝衰竭治疗中的意义和潜在价值[J]. 临床肝胆病杂志, 2022, 38(3): 708-713. DOI: 10.3969/j.issn.1001-5256.2022.03.044.
    [43]
    WANG Y, LI X, CHEN Q, et al. Histone deacetylase 6 regulates the activation of M1 macrophages by the glycolytic pathway during acute liver failure[J]. J Inflamm Res, 2021, 14: 1473-1485. DOI: 10.2147/JIR.S302391.
    [44]
    WANG XF, SHI QL, WANG MG, et al. Experimental study on effect of Jiedu Huayu granules on hepatic mitochondrial permeability transition in rats with acute liver failure[J]. Liaoning J Tradit Chin Med, 2017, 44(10): 2186-2189. DOI: 10.13192/j.issn.1000-1719.2017.10.056.

    王秀峰, 石清兰, 王明刚, 等. 解毒化瘀颗粒抑制急性肝衰竭大鼠肝线粒体通透性转换的实验研究[J]. 辽宁中医杂志, 2017, 44(10): 2186-2189. DOI: 10.13192/j.issn.1000-1719.2017.10.056.
    [45]
    ZHANG RZ, MAO DW, SUN KW, et al. Mechanism of action of Jieduhuayu granules for remission of oxidative stress in hepatocytes[J]. Chin J Hepatol, 2021, 29(12): 1188-1193. DOI: 10.3760/cma.j.cn501113-20210721-00349.

    张荣臻, 毛德文, 孙克伟, 等. 解毒化瘀颗粒缓解肝细胞氧化应激的作用机制[J]. 中华肝脏病杂志, 2021, 29(12): 1188-1193. DOI: 10.3760/cma.j.cn501113-20210721-00349.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (1373) PDF downloads(132) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return