动力蛋白相关蛋白1（Drp1）在非酒精性脂肪性肝病中的作用

沈海珊, 王数, 冯巩

PDF(771 KB)
中国高校科技期刊信息汇聚平台
PDF(771 KB)
临床肝胆病杂志 ›› 2025, Vol. 41 ›› Issue (1) : 159-163. DOI: 10.12449/JCH250124
综述

动力蛋白相关蛋白1（Drp1）在非酒精性脂肪性肝病中的作用

作者信息 +

Role of dynamin-related protein 1 in non-alcoholic fatty liver disease

Author information +
History +

摘要

线粒体的形态变化和功能与非酒精性脂肪性肝病（NAFLD）的发生发展密切相关。动力蛋白相关蛋白1（Drp1）是决定线粒体分裂的最主要蛋白之一，其活性受到严格控制，根据细胞需要确保线粒体动力学的平衡。Drp1可通过促进内质网小管形成，促进线粒体的相互作用和分裂。Drp1的磷酸化状态及去乙酰化也可影响线粒体的形态变化，从而影响NAFLD的疾病状态。本文阐述了Drp1在NAFLD进展中的作用及机制，为靶向治疗NAFLD提供思路。

Abstract

The morphological changes and functions of mitochondria are closely associated with the development and progression of non-alcoholic fatty liver disease （NAFLD）. Dynamin-related protein 1 （Drp1） is one of the primary proteins determining mitochondrial fission， and its activity is strictly controlled to ensure the balance of mitochondrial dynamics according to cellular needs. Drp1 can enhance mitochondrial interactions and mitochondrial fission by promoting the formation of endoplasmic reticulum tubules， and the phosphorylation state and deacetylation of Drp1 can also affect the morphological changes of mitochondria， thereby affecting the status of NAFLD. This article elaborates on the role and mechanism of action of Drp1 in the progression of NAFLD， in order to provide ideas for targeted therapy for NAFLD.

关键词

非酒精性脂肪性肝病 / 动力蛋白 / 线粒体

Key words

Non-alcoholic Fatty Liver Disease / Dyneins / Mitochondria

引用本文

EndNote

Ris (Procite)

Bibtex

导出引用
沈海珊 , 王数 , 冯巩. 动力蛋白相关蛋白1（Drp1）在非酒精性脂肪性肝病中的作用. 临床肝胆病杂志. 2025, 41(1): 159-163 https://doi.org/10.12449/JCH250124
Haishan SHEN, Shuo WANG, Gong FENG. Role of dynamin-related protein 1 in non-alcoholic fatty liver disease[J]. Journal of Clinical Hepatol. 2025, 41(1): 159-163 https://doi.org/10.12449/JCH250124

参考文献

列表( 原文顺序 | 文献年度倒序 | 文中引用次数倒序 ) 可视化分析
1
WONG VWS, EKSTEDT M, WONG GLH, et al. Changing epidemiology, global trends and implications for outcomes of NAFLD[J]. J Hepatol, 2023, 79(3): 842-852. DOI: 10.1016/j.jhep.2023.04.036 .
本文引用 [1]
2
KOKKORAKIS M, BOUTARI C, HILL MA, et al. Resmetirom, the first approved drug for the management of metabolic dysfunction-associated steatohepatitis: Trials, opportunities, and challenges[J]. Metabolism, 2024, 154: 155835. DOI: 10.1016/j.metabol.2024.155835 .
本文引用 [1]
3
SHUM M, NGO J, SHIRIHAI OS, et al. Mitochondrial oxidative function in NAFLD: Friend or foe?[J]. Mol Metab, 2021, 50: 101134. DOI: 10.1016/j.molmet.2020.101134 .
本文引用 [2]
4
WU LW, MO WH, FENG J, et al. Astaxanthin attenuates hepatic damage and mitochondrial dysfunction in non-alcoholic fatty liver disease by up-regulating the FGF21/PGC-1α pathway[J]. Br J Pharmacol, 2020, 177(16): 3760-3777. DOI: 10.1111/bph.15099 .
本文引用 [1]
5
PARADIES G, PARADIES V, RUGGIERO FM, et al. Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2014, 20(39): 14205-14218. DOI: 10.3748/wjg.v20.i39.14205 .
本文引用 [1]
6
YU LP, LI YJ, WANG T, et al. In vivo recognition of bioactive substances of Polygonum multiflorum for protecting mitochondria against metabolic dysfunction-associated fatty liver disease[J]. World J Gastroenterol, 2023, 29(1): 171-189. DOI: 10.3748/wjg.v29.i1.171 .
本文引用 [1]
7
di CIAULA A, PASSARELLA S, SHANMUGAM H, et al. Nonalcoholic fatty liver disease (NAFLD). Mitochondria as players and targets of therapies?[J]. Int J Mol Sci, 2021, 22(10): 5375. DOI: 10.3390/ijms22105375 .
本文引用 [1]
8
MORIO B, PANTHU B, BASSOT A, et al. Role of mitochondria in liver metabolic health and diseases[J]. Cell Calcium, 2021, 94: 102336. DOI: 10.1016/j.ceca.2020.102336 .
本文引用 [1]
9
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. DOI: 10.1016/j.cmet.2015.04.004 .
本文引用 [2]
10
MANSOURI A, GATTOLLIAT CH, ASSELAH T. Mitochondrial dysfunction and signaling in chronic liver diseases[J]. Gastroenterology, 2018, 155(3): 629-647. DOI: 10.1053/j.gastro.2018.06.083 .
本文引用 [1]
11
IOZZO P, BUCCI M, ROIVAINEN A, et al. Fatty acid metabolism in the liver, measured by positron emission tomography, is increased in obese individuals[J]. Gastroenterology, 2010, 139(3): 846-856. e1-e6. DOI: 10.1053/j.gastro.2010.05.039 .
本文引用 [1]
12
SUNNY NE, PARKS EJ, BROWNING JD, et al. Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease[J]. Cell Metab, 2011, 14(6): 804-810. DOI: 10.1016/j.cmet.2011.11.004 .
本文引用 [2]
13
MCGARRY JD, MANNAERTS GP, FOSTER DW. A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis[J]. J Clin Invest, 1977, 60(1): 265-270. DOI: 10.1172/JCI108764 .
本文引用 [1]
14
SATAPATI S, KUCEJOVA B, DUARTE JAG, et al. Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver[J]. J Clin Invest, 2015, 125(12): 4447-4462. DOI: 10.1172/JCI82204 .
本文引用 [1]
15
COGLIATI S, ENRIQUEZ JA, SCORRANO L. Mitochondrial cristae: Where beauty meets functionality[J]. Trends Biochem Sci, 2016, 41(3): 261-273. DOI: 10.1016/j.tibs.2016.01.001 .
本文引用 [1]
16
FORMOSA LE, RYAN MT. Mitochondrial OXPHOS complex assembly lines[J]. Nat Cell Biol, 2018, 20(5): 511-513. DOI: 10.1038/s41556-018-0098-z .
本文引用 [1]
17
WAI T, LANGER T. Mitochondrial dynamics and metabolic regulation[J]. Trends Endocrinol Metab, 2016, 27(2): 105-117. DOI: 10.1016/j.tem.2015.12.001 .
本文引用 [1]
18
EISNER V, PICARD M, HAJNÓCZKY G. Mitochondrial dynamics in adaptive and maladaptive cellular stress responses[J]. Nat Cell Biol, 2018, 20(7): 755-765. DOI: 10.1038/s41556-018-0133-0 .
本文引用 [1]
19
SIMULA L, CAMPANELLA M, CAMPELLO S. Targeting Drp1 and mitochondrial fission for therapeutic immune modulation[J]. Pharmacol Res, 2019, 146: 104317. DOI: 10.1016/j.phrs.2019.104317 .
本文引用 [1]
20
STRACK S, CRIBBS JT. Allosteric modulation of Drp1 mechanoenzyme assembly and mitochondrial fission by the variable domain[J]. J Biol Chem, 2012, 287(14): 10990-11001. DOI: 10.1074/jbc.M112.342105 .
本文引用 [1]
21
FRÖHLICH C, GRABIGER S, SCHWEFEL D, et al. Structural insights into oligomerization and mitochondrial remodelling of dynamin 1-like protein[J]. EMBO J, 2013, 32(9): 1280-1292. DOI: 10.1038/emboj.2013.74 .
本文引用 [1]
22
KISHIDA H, SUGIO S. Crystal structure of GTPase domain fused with minimal stalks from human dynamin-1-like protein (Dlp1) in complex with several nucleotide analogues[J]. Curr Top Pept Protein Res, 2013, 14: 67-77.
本文引用 [1]
23
RAMACHANDRAN R, SCHMID SL. The dynamin superfamily[J]. Curr Biol, 2018, 28(8): R411-R416. DOI: 10.1016/j.cub.2017.12.013 .
本文引用 [1]
24
JOSHI AU, SAW NL, SHAMLOO M, et al. Drp1/Fis1 interaction mediates mitochondrial dysfunction, bioenergetic failure and cognitive decline in Alzheimer’s disease[J]. Oncotarget, 2017, 9(5): 6128-6143. DOI: 10.18632/oncotarget.23640 .
本文引用 [1]
25
JIN JY, WEI XX, ZHI XL, et al. Drp1-dependent mitochondrial fission in cardiovascular disease[J]. Acta Pharmacol Sin, 2021, 42(5): 655-664. DOI: 10.1038/s41401-020-00518-y .
本文引用 [1]
26
YU R, LIU T, JIN SB, et al. MIEF1/2 function as adaptors to recruit Drp1 to mitochondria and regulate the association of Drp1 with Mff[J]. Sci Rep, 2017, 7(1): 880. DOI: 10.1038/s41598-017-00853-x .
本文引用 [1]
27
SOUNDARARAJAN R, HERNÁNDEZ-CUERVO H, STEARNS TM, et al. A-kinase anchor protein 1 deficiency causes mitochondrial dysfunction in mouse model of hyperoxia induced acute lung injury[J]. Front Pharmacol, 2022, 13: 980723. DOI: 10.3389/fphar.2022.980723 .
本文引用 [2]
28
CRIBBS JT, STRACK S. Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death[J]. EMBO Rep, 2007, 8(10): 939-944. DOI: 10.1038/sj.embor.7401062 .
本文引用 [1]
29
ADACHI Y, KATO T, YAMADA T, et al. Drp1 tubulates the ER in a GTPase-independent manner[J]. Mol Cell, 2020, 80(4): 621-632. e6. DOI: 10.1016/j.molcel.2020.10.013 .
本文引用 [2]
30
NAVARATNARAJAH T, ANAND R, REICHERT AS, et al. The relevance of mitochondrial morphology for human disease[J]. Int J Biochem Cell Biol, 2021, 134: 105951. DOI: 10.1016/j.biocel.2021.105951 .
本文引用 [1]
31
WANG LX, ISHIHARA T, IBAYASHI Y, et al. Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration[J]. Diabetologia, 2015, 58(10): 2371-2380. DOI: 10.1007/s00125-015-3704-7 .
本文引用 [1]
32
GALLOWAY CA, LEE H, BROOKES PS, et al. Decreasing mitochondrial fission alleviates hepatic steatosis in a murine model of nonalcoholic fatty liver disease[J]. Am J Physiol Gastrointest Liver Physiol, 2014, 307(6): G632-G641. DOI: 10.1152/ajpgi.00182.2014 .
本文引用 [1]
33
HAMMERSCHMIDT P, OSTKOTTE D, NOLTE H, et al. CerS6-derived sphingolipids interact with mff and promote mitochondrial fragmentation in obesity[J]. Cell, 2019, 177(6): 1536-1552. e23. DOI: 10.1016/j.cell.2019.05.008 .
本文引用 [1]
34
XIA WM, VEERAGANDHAM P, CAO Y, et al. Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation[J]. Nat Metab, 2024, 6(2): 273-289. DOI: 10.1038/s42255-024-00978-0 .
本文引用 [1]
35
FRIEDMAN JR, LACKNER LL, WEST M, et al. ER tubules mark sites of mitochondrial division[J]. Science, 2011, 334(6054): 358-362. DOI: 10.1126/science.1207385 .
本文引用 [1]
36
BRAVO-SAGUA R, PARRA V, ORTIZ-SANDOVAL C, et al. Caveolin-1 impairs PKA-DRP1-mediated remodelling of ER-mitochondria communication during the early phase of ER stress[J]. Cell Death Differ, 2019, 26(7): 1195-1212. DOI: 10.1038/s41418-018-0197-1 .
本文引用 [1]
37
STEFFEN J, NGO J, WANG SP, et al. The mitochondrial fission protein Drp1 in liver is required to mitigate NASH and prevents the activation of the mitochondrial ISR[J]. Mol Metab, 2022, 64: 101566. DOI: 10.1016/j.molmet.2022.101566 .
本文引用 [1]
38
WANG J, YANG Y, SUN F, et al. ALKBH5 attenuates mitochondrial fission and ameliorates liver fibrosis by reducing Drp1 methylation[J]. Pharmacol Res, 2023, 187: 106608. DOI: 10.1016/j.phrs.2022.106608 .
本文引用 [1]
39
HU ZQ, ZHANG HY, WANG YT, et al. Exercise activates Sirt1-mediated Drp1 acetylation and inhibits hepatocyte apoptosis to improve nonalcoholic fatty liver disease[J]. Lipids Health Dis, 2023, 22(1): 33. DOI: 10.1186/s12944-023-01798-z .
本文引用 [1]
40
LEMOS V, DE OLIVEIRA RM, NAIA LA, et al. The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes[J]. Hum Mol Genet, 2017, 26(21): 4105-4117. DOI: 10.1093/hmg/ddx298 .
本文引用 [1]
41
ZHANG LW, XIE XX, TAO JX, et al. Mystery of bisphenol F-induced nonalcoholic fatty liver disease-like changes: Roles of Drp1-mediated abnormal mitochondrial fission in lipid droplet deposition[J]. Sci Total Environ, 2023, 904: 166831. DOI: 10.1016/j.scitotenv.2023.166831 .
本文引用 [1]
42
QUAN Y, SHOU DW, YANG SQ, et al. Mdivi1 ameliorates mitochondrial dysfunction in non-alcoholic steatohepatitis by inhibiting JNK/MFF signaling[J]. J Gastroenterol Hepatol, 2023, 38(12): 2215-2227. DOI: 10.1111/jgh.16372 .
本文引用 [1]
43
ZHONG YJ, LI ZM, JIN RY, et al. Diosgenin ameliorated type II diabetes-associated nonalcoholic fatty liver disease through inhibiting de novo lipogenesis and improving fatty acid oxidation and mitochondrial function in rats[J]. Nutrients, 2022, 14(23): 4994. DOI: 10.3390/nu14234994 .
本文引用 [1]
44
DU JX, WANG TT, XIAO CY, et al. Pharmacological activation of AMPK prevents Drp1-mediated mitochondrial fission and alleviates hepatic steatosis In vitro[J]. Curr Mol Med, 2024, 24(12): 1506-1517. DOI: 10.2174/0115665240275594231229121030 .
本文引用 [1]

作者贡献声明

沈海珊负责设计论文框架，起草论文；王数负责文献检索及修改文章；冯巩负责论文修改，拟定写作思路，指导撰写文章并最后定稿。

评论

PDF(771 KB)

Accesses

Citation

Detail
段落导航
相关文章
Copyright 中国高校科技期刊信息汇聚平台 2024-2025
技术支持：北京玛格泰克科技发展有限公司
京ICP备05021913号-19

/

〈 〉