网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
Drp1介导的线粒体裂变在肌萎缩侧索硬化中的研究进展
作者:胡宇静  张莹  姜宏佺 
单位:哈尔滨医科大学附属第一医院 神经内科, 黑龙江 哈尔滨 150001
关键词:肌萎缩侧索硬化 线粒体动力相关蛋白1 线粒体裂变 综述 
分类号:R744.8
出版年·卷·期(页码):2023·51·第六期(864-868)
摘要:

肌萎缩性侧索硬化(ALS)是运动神经元病中最常见的类型,随着上下运动神经元的丢失病情不断恶化,尚无有效治疗方法。线粒体功能障碍是ALS的重要发病机制之一。线粒体是产生 ATP 的主要细胞器,以高度动态的形式存在,通过不断的裂变与融合维持线粒体的形态、质量和功能,保证细胞正常活动。线粒体动力相关蛋白1(Drp1)是驱动线粒体裂变的主要调节因子,其功能异常与ALS的发病机制密切相关。抑制Drp1导致的线粒体过度碎片化、减少线粒体损伤可能成为ALS防治的新靶点。本文作者对Drp1的结构及其介导的裂变功能在ALS中的研究进展进行综述。

参考文献:

[1] OSKARSSON B,GENDRON T F,STAFF N P.Amyotrophic lateral sclerosis:an update for 2018[J].Mayo Clin Proc,2018,93(11):1617-1628.
[2] VUCIC S,ROTHSTEIN J D,KIERNAN M C.Advances in treating amyotrophic lateral sclerosis:insights from pathophysiological studies[J].Trends Neurosci,2014,37(8):433-442.
[3] LAMBERT-SMITH I A,SAUNDERS D N,YERBURY J J.Progress in biophysics and molecular biology proteostasis impairment and ALS[J].Prog Biophys Mol Biol,2022,174:3-27.
[4] YU W,HE J,CAI X,et al.Neuroimmune crosstalk between the peripheral and the central immune system in amyotrophic lateral sclerosis[J].Front Aging Neurosci,2022,14:890958.
[5] DORN G W 2ND,DANG X W.Predicting mitochondrial dynamic behavior in genetically defined neurodegenerative diseases[J].Cells,2022,11(6):1049.
[6] BERA A,LAVANYA G,RESHMI R,et al.Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer's disease[J].Eur J Neurosci,2022,56(9):5516-5531.
[7] REDDY P H,REDDY T P,MANCZAK M,et al.Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases[J].Brain Res Rev,2011,67(1-2):103-118.
[8] HO D H,JE A R,LEE H,et al.LRRK2 kinase activity induces mitochondrial fission in microglia via Drp1 and modulates neuroinflammation[J].Exp Neurobiol,2018,27(3):171-180.
[9] OLIVER D,REDDY P H.Dynamics of dynamin-related protein 1 in Alzheimer's disease and other neurodegenerative diseases[J].Cells,2019,8(9):961.
[10] TAN Z,ZHAO M,LI J,et al.Myostatin is involved in skeletal muscle dysfunction in chronic obstructive pulmonary disease via Drp-1 mediated abnormal mitochondrial division[J].Ann Transl Med,2022,10(4):162.
[11] JOSHI A U,SAW N L,VOGEL H,et al.Inhibition of Drp1/Fis1 interaction slows progression of amyotrophic lateral sclerosis[J].EMBO Mol Med,2018,10(3):e8166.
[12] GAO J,WANG L,LIU J,et al.Abnormalities of mitochondrial dynamics in neurodegenerative diseases[J].Antioxidants(Basel),2017,6(2):25.
[13] QI Z,HUANG Z,XIE F,et al.Dynamin-related protein 1:a critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases[J].J Cell Physiol,2019,234(7):10032-10046.
[14] YIM N,RYU S W,HAN E C,et al.Mutant ubiquitin UBB+1 induces mitochondrial fusion by destabilizing mitochondrial fission-specific proteins and confers resistance to oxidative stress-induced cell death in astrocytic cells[J].PLoS One,2014,9(6):e99937.
[15] YANG Y,LEI W,ZHAO L,et al.Insights into mitochondrial dynamics in chlamydial infection[J].Front Cell Infect Microbiol,2022,12:835181.
[16] QU C,YANG W,KAN Y,et al.RhoA/ROCK signaling regulates Drp1-mediated mitochondrial fission during collective cell migration[J].Front Cell Dev Biol,2022,10:882581.
[17] TILOKANI L,NAGASHIMA S,PAUPE V,et al.Mitochondrial dynamics:overview of molecular mechanisms[J].Essays Biochem,2018,62(3):341-360.
[18] WEN S,AKI T,FUNAKOSHI T,et al.Role of mitochondrial dynamics in cocaine's neurotoxicity[J].Int J Mol Sci,2022,23(10):5418.
[19] MIWA S,KASHYAP S,CHINI E,et al.Mitochondrial dysfunction in cell senescence and aging[J].J Clin Invest,2022,132(13):e158447.
[20] PATERGNANI S,MORCIANO G,CARINCI M,et al.The “mitochondrial stress responses”:the “Dr.Jekyll and Mr.Hyde” of neuronal disorders[J].Neural Regen Res,2022,17(12):2563-2575.
[21] SONG J,YI X,GAO R,et al.Impact of Drp1-mediated mitochondrial dynamics on T cell immune modulation[J].Front Immunol,2022,13:873834.
[22] GIACOMELLO M,PYAKUREL A,GLYTSOU C,et al.The cell biology of mitochondrial membrane dynamics[J].Nat Rev Mol Cell Biol,2020,21(4):204-224.
[23] JOILIN G,LEIGH P N,NEWBURY S F,et al.An overview of microRNAs as biomarkers of ALS[J].Front Neurol,2019,10:186.
[24] ZHOU Y,ZHEN Y,WANG G,et al.Deconvoluting the complexity of reactive oxygen species(ROS) in neurodegenerative diseases[J].Front Neuroanat,2022,16:910427.
[25] MAGRANÉ J,MANFREDI G.Mitochondrial function,morphology,and axonal transport in amyotrophic lateral sclerosis[J].Antioxid Redox Signal,2009,11(7):1615-1626.
[26] REDDY P H,REDDY T P,MANCZAK M,et al.Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases[J].Brain Research Reviews,2011,67(1-2):103-118.
[27] SONG W,SONG Y,KINCAID B,et al.Mutant SOD1G93A triggers mitochondrial fragmentation in spinal cord motor neurons:neuroprotection by SIRT3 and PGC-1α[J].Neurobiol Dis,2013,51:72-81.
[28] ALTANBYEK V,CHA S J,KANG G U,et al.Imbalance of mitochondrial dynamics in drosophila models of amyotrophic lateral sclerosis[J].Biochem Biophys Res Commun,2016,481(3-4):259-264.
[29] WANG H,YI J,LI X,et al.ALS-associated mutation SOD1(G93A) leads to abnormal mitochondrial dynamics in osteocytes[J].Bone,2018,106:126-138.
[30] JOSHI A U,SAW N L,VOGEL H,et al.Inhibition of Drp1/Fis1 interaction slows progression of amyotrophic lateral sclerosis[J].EMBO molecular medicine,2018,10(3):e8166.
[31] PETROZZIELLO T,BORDT E A,MILLS A N,et al.Targeting tau mitigates mitochondrial fragmentation and oxidative stress in amyotrophic lateral sclerosis[J].Mol Neurobiol,2022,59(1):683-702.
[32] BODAKUNTLA S,JIJUMON A S,VILLABLANCA C,et al.Microtubule-associated proteins:structuring the cytoskeleton[J].Trends Cell Biol,2019,29(10):804-819.
[33] MUYDERMAN H,CHEN T.Mitochondrial dysfunction in amyotrophic lateral sclerosis-a valid pharmacological target?[J].Br J Pharmacol,2014,171(8):2191-2205.
[34] SMITH E F,SHAW P J,DE VOS K J.The role of mitochondria in amyotrophic lateral sclerosis[J].Neurosci Lett,2019,710:132933.
[35] HU C,HUANG Y,LI L.Drp1-dependent mitochondrial fission plays critical roles in physiological and pathological progresses in mammals[J].Int J Mol Sci,2017,18(1):144.
[36] CARRì M T,D'AMBROSI N,COZZOLINO M.Pathways to mitochondrial dysfunction in ALS pathogenesis[J].Biochem Biophys Res Commun,2017,483(4):1187-1193.
[37] STEIN J,WALKENFORT B,CIHANKAYA H,et al.Increased ros-dependent fission of mitochondria causes abnormal morphology of the cell powerhouses in a murine model of amyotrophic lateral sclerosis[J].Oxid Med Cell Longev,2021,2021:6924251.
[38] KNOTT A B,PERKINS G,SCHWARZENBACHER R,et al.Mitochondrial fragmentation in neurodegeneration[J].Nat Rev Neurosci,2008,9(7):505-518.
[39] CHOI S Y,LEE J H,CHUNG A Y,et al.Prevention of mitochondrial impairment by inhibition of protein phosphatase 1 activity in amyotrophic lateral sclerosis[J].Cell Death & Disease,2020,11(10):888.
[40] WANG N,PRABHAKAR N R,NANDURI J.Protein phosphatase 1 regulates reactive oxygen species-dependent degradation of histone deacetylase 5 by intermittent hypoxia[J].Am J Physiol Cell Physiol,2022,323(2):C423-C443.
[41] MANIATIS S,ÄIJÖ T,VICKOVIC S,et al.Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis[J].Science,2019,364(6435):89-93.
[42] CHOI S Y,KIM J Y,KIM H W,et al.Drp1-mediated mitochondrial dynamics and survival of developing chick motoneurons during the period of normal programmed cell death[J].FASEB J,2013,27(1):51-62.
[43] ROTUNNO M S,BOSCO D A.An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis[J].Front Cell Neurosci,2013,7:253.
[44] CHOU C-C,ZHANG Y,UMOH M E,et al.TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD[J].Nat Neurosci,2018,21(2):228-239.
[45] WANG P,DENG J,DONG J,et al.TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response[J].PLoS Genet,2019,15(5):e1007947.
[46] CHO B,CHO H M,KIM H J,et al.CDK5-dependent inhibitory phosphorylation of Drp1 during neuronal maturation[J].Exp Mol Med,2014,46(7):e105.
[47] LI H,ALAVIAN K N,LAZROVE E,et al.A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis[J].Nat Cell Biol,2013,15(7):773-785.
[48] BEREITER-HAHN J,JENDRACH M.Mitochondrial dynamics[J].Int Rev Cell Mol Biol,2010,284:1-65.
[49] CHO H M,RYU J R,JO Y,et al.Drp1-Zip1 interaction regulates mitochondrial quality surveillance system[J].Mol Cell,2019,73(2):364-376.e8.
[50] CHEN Y,CULETTO E,LEGOUIS R.The strange case of Drp1 in autophagy:Jekyll and Hyde?[J].Bioessays,2022,44(4):e2100271.
[51] TWIG G,ELORZA A,MOLINA A J,et al.Fission and selective fusion govern mitochondrial segregation and elimination by autophagy[J].Embo J,2008,27(2):433-446.
[52] NEMTSOVA Y,STEINERT B L,WHARTON K A.Compartment specific mitochondrial dysfunction in Drosophila knock-in model of ALS reversed by altered gene expression of OXPHOS subunits and pro-fission factor Drp1[J].Mol Cell Neurosci,2023,125:103834.
[53] FILIPPINI A,D'AMORE A,D'ALESSIO A.Calcium mobilization in endothelial cell functions[J].Int J Mol Sci,2019,12;20(18):4525.
[54] YAMASHITA R,FUJII S,USHIODA R,et al.Ca2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation[J].Sci Rep,2021,11(1):20772.
[55] WALCZAK J,DBSKA-VIELHABER G,VIELHABER S,et al.Distinction of sporadic and familial forms of ALS based on mitochondrial characteristics[J].FASEB J,2019,33(3):4388-4403.
[56] CEREGHETTI G M,STANGHERLIN A,MARTINS D B O,et al.Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria[J].Proc Natl Acad Sci U S A,2008,105(41):15803-15808.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 752387 位访问者


 ©《现代医学》编辑部
联系电话:025-83272481;83272479
电子邮件: xdyx@pub.seu.edu.cn

苏ICP备09058541