线粒体功能异常在非酒精性脂肪性肝病发生中的机制

徐梓馨; 罗声政; 徐铭益

doi:10.3969/j.issn.1001-5256.2020.10.042

线粒体功能异常在非酒精性脂肪性肝病发生中的机制

DOI: 10.3969/j.issn.1001-5256.2020.10.042

上海交通大学附属第一人民医院消化内科

基金项目:

国家自然科学基金(81570547,81770597)；国家科技部“十三五”重大专项(2017ZX10203202003005)；

详细信息

中图分类号: R575.5
计量
- 文章访问数: 931
- HTML全文浏览量: 79
- PDF下载量: 130
- 被引次数: 0
出版历程
- 收稿日期: 2020-04-24
- 出版日期: 2020-10-20

Mechanism of mitochondrial dysfunction in the development of nonalcoholic fatty liver disease

Department of Gastroenterology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine

Research funding:

摘要

摘要: 非酒精性脂肪性肝病(NAFLD)是一个复杂的、多因素影响的一些系列的疾病。线粒体功能障碍常发生在NAFLD中,并导致肝炎、肝纤维化的进展。阐述了线粒体氧化应激、呼吸作用、能量代谢、质量控制以及线粒体DNA在NAFLD中发挥的重要作用,并总结了NAFLD的线粒体靶向治疗现状,希望为NAFLD的研究及临床治疗提供新的方向。
- 非酒精性脂肪性肝病 /
- 线粒体 /
- 分子靶向治疗
Abstract: Nonalcoholic fatty liver disease( NAFLD) includes a series of diseases affected by various complex factors. Mitochondrial dysfunction often occurs in NAFLD and may lead to the progression of hepatitis and liver fibrosis. This article reviews the important role of mitochondrial oxidative stress,respiration,energy metabolism,quality control,and mitochondrial DNA in NAFLD and summarizes the current status of mitochondria-targeted therapy for NAFLD,hoping to provide a new direction for the research and clinical treatment of NAFLD.
- nonalcoholic fatty liver disease /
- mitochondria /
- molecular targeted therapy

HTML全文

参考文献(30)

[1] YOUNES R,BUGIANESI E. A spotlight on pathogenesis,interactions and novel therapeutic options in NAFLD[J]. Nat Rev Gastroenterol Hepatol,2019,16(2):80-82.

[2] JIANG YZ,NIE HM,WANG R. Research advances in the pathogenesis of nonalcoholic fatty liver disease[J]. J Clin Hepatol,2019,35(11):2588-2591.(in Chinese)姜煜资，聂红明，汪蓉．非酒精性脂肪性肝病的发病机制[J]．临床肝胆病杂志，2019,35(11):2588-2591.

[3] THANAPIROM K,TSOCHATZIS EA. Non-alcoholic fatty liver disease(NAFLD)and the quest for effective treatments[J].Hepatobiliary Surg Nutr,2019,8(1):77-79.

[4] LI Z,LI Y,ZHANG HX,et al. Mitochondria-mediated pathogenesis and therapeutics for non-alcoholic fatty liver disease[J]. Mol Nutr Food Res,2019,63(16):e1900043.

[5] OSELLAME LD,BLACKER TS,DUCHEN MR. Cel ular and molecular mechanisms of mitochondrial function[J]. Best Pract Res Clin Endocrinol Metab,2012,26(6):711-723.

[6] HERZIG S,SHAW RJ. AMPK:Guardian of metabolism and mitochondrial homeostasis[J]. Nat Rev Mol Cell Biol,2018,19(2):121-135.

[7] UPADHYAY KK,JADEJA RN,VYAS HS,et al. Carbon monoxide releasing molecule-A1 improves nonalcoholic steatohepatitis via Nrf2 activation mediated improvement in oxidative stress and mitochondrial function[J]. Redox Biol,2020,28:101314.

[8] CHEN L,LIU L,LI C,et al. A mix of apple pomace polysaccharide improves mitochondrial function and reduces oxidative stress in the liver of high-fat diet-induced obese mice[J].Mol Nutr Food Res,2017,61(3):10.

[9] KIM CS,KWON Y,CHOE SY,et al. Quercetin reduces obesity-induced hepatosteatosis by enhancing mitochondrial oxidative metabolism via heme oxygenase-1[J]. Nutr Metab(Lond),2015,12:33.

[10] CHO J,ZHANG Y,PARK SY,et al. Corrigendum:Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance[J]. Nat Commun,2017,8:16143.

[11] BELLANTI F,VILLANI R,TAMBORRA R,et al. Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression[J]. Redox Biol,2018,15:86-96.

[12] MOTA M,BANINI BA,CAZANAVE SC,et al. Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease[J]. Metabolism,2016,65(8):1049-1061.

[13] LEE K,HADDAD A,OSME A,et al. Hepatic mitochondrial defects in a nonalcoholic fatty liver disease mouse model are associated with increased degradation of oxidative phosphorylation subunits[J]. Mol Cell Proteomics,2018,17(12):2371-2386.

[14] SPAHIS S,DELVIN E,BORYS JM,et al. Oxidative stress as a critical factor in nonalcoholic fatty liver disease pathogenesis[J]. Antioxid Redox Signal,2017,26(10):519-541.

[15] LIU Y,MU D,CHEN H,et al. Retinol-binding protein 4 induces hepatic mitochondrial dysfunction and promotes hepatic steatosis[J]. J Clin Endocrinol Metab,2016,101(11):4338-4348.

[16] ZHENG Y,QU H,XIONG X,et al. Deficiency of mitochondrial glycerol 3-phosphate dehydrogenase contributes to hepatic steatosis[J]. Hepatology,2019,70(1):84-97.

[17] CHEN J,FAN X,ZHOU L,et al. Treatment with geraniol ameliorates methionine-choline-deficient diet-induced non-alcoholic steatohepatitis in rats[J]. J Gastroenterol Hepatol,2016,31(7):1357-1365.

[18] SHELDON RD,MEERS GM,MORRIS EM,et al. e NOS deletion impairs mitochondrial quality control and exacerbates Western diet-induced NASH[J]. Am J Physiol Endocrinol Metab,2019,317(4):e605-e616.

[19] ZHOU H,DU W,LI Y,et al. Effects of melatonin on fatty liver disease:The role of NR4A1/DNA-PKcs/p53 pathway,mitochondrial fission,and mitophagy[J]. J Pineal Res,2018,64(1):10.

[20] ZHOU T,CHANG L,LUO Y,et al. Corrigendum to“Mst1 inhibition attenuates non-alcoholic fatty liver disease via reversing Parkin-related mitophagy”[Redox Biol. 21(2019 Feb)101120][J]. Redox Biol,2020,28:101299.

[21] LIU P,LIN H,XU Y,et al. Frataxin-mediated PINK1-parkindependent mitophagy in hepatic steatosis:The protective effects of quercetin[J]. Mol Nutr Food Res,2018,62(16):e1800164.

[22] MALIK AN,SIMES I,ROSA HS,et al. A diet induced maladaptive increase in hepatic mitochondrial DNA precedes OXPHOS defects and may contribute to non-alcoholic fatty liver disease[J]. Cells,2019,8(10):1222.

[23] KOLIAKI C,SZENDROEDI J,KAUL K,et al. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis[J]. Cell Metab,2015,21(5):739-746.

[24] SOOKOIAN S,FLICHMAN D,SCIAN R,et al. Mitochondrial genome architecture in non-alcoholic fatty liver disease[J].J Pathol,2016,240(4):437-449.

[25] MCCARTHY CG,WENCESLAU CF,GOULOPOULOU S,et al.Circulating mitochondrial DNA and Tol-like receptor 9 are associated with vascular dysfunction in spontaneously hypertensive rats[J]. Cardiovasc Res,2015,107(1):119-130.

[26] PAN J,OU Z,CAI C,et al. Fatty acid activates NLRP3 inflammasomes in mouse Kupffer cells through mitochondrial DNA release[J]. Cell Immunol,2018,332:111-120.

[27] KHOO N,FAZZARI M,CHARTOUMPEKIS DV,et al. Electrophilic nitro-oleic acid reverses obesity-induced hepatic steatosis[J]. Redox Biol,2019,22:101132.

[28] RATZIU V,GIRAL P,JACQUEMINET S,et al. Rosiglitazone for nonalcoholic steatohepatitis:One-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy(FLIRT)Trial[J]. Gastroenterology,2008,135(1):100-110.

[29] GOEDEKE L,PENG L,MONTALVO-ROMERAL V,et al. Control ed-release mitochondrial protonophore(CRMP)reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates[J]. Sci Transl Med,2019,11(512):eaay0284.

[30] PERRY RJ,ZHANG D,ZHANG XM,et al. Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats[J]. Science,2015,347(6227):1253-1256.

施引文献

资源附件(0)

访问统计