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J Zhejiang Univ (Med Sci)  2021, Vol. 50 Issue (3): 403-408    DOI: 10.3724/zdxbyxb-2021-0163
    
Progress on mitochondrial silence information regulator family in epilepsy
ZHU Feng1(),XIANG Yingchun2,ZENG Linghui1,*()
1. School of Medicine, Zhejiang University City College, Hangzhou 310015, China;
2. Department of Pharmacy, Zhejiang Hospital, Hangzhou 310012 ,China
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Abstract  

SIRT3, SIRT4 and SIRT5 are located in mitochondria and also known as mitochondrial sirtuins. They play important roles in regulating many cellular functions including cell survival, cell cycle or apoptosis, DNA repair and metabolism. Mitochondrial sirtuins are involved in the protection of mitochondrial integrity and energy metabolism under stress regulating the expression of neurotransmitter receptors, neurotrophins, extracellular matrix proteins and various transcription factors, thus involved in epileptogenesis triggered by both genetic or acquired factors. Here we review research progress on the actions of mitochondrial sirtuin in epilepsy; and discuss the challenges and perspectives of mitochondrial sirtuin as a potential therapeutic target for epilepsy.



Key wordsMitochondrion      Silence information regulator      Epilepsy      Oxidative stress      Mechanism      Review     
Received: 20 October 2020      Published: 16 August 2021
CLC:  R742.1  
Corresponding Authors: ZENG Linghui     E-mail: zhuf@zucc.edu.cn;zenglh@zucc.edu.cn
Cite this article:

ZHU Feng,XIANG Yingchun,ZENG Linghui. Progress on mitochondrial silence information regulator family in epilepsy. J Zhejiang Univ (Med Sci), 2021, 50(3): 403-408.

URL:

http://www.zjujournals.com/med/10.3724/zdxbyxb-2021-0163     OR     http://www.zjujournals.com/med/Y2021/V50/I3/403


线粒体沉默信息调节因子家族在癫痫发生发展中的作用研究进展

线粒体沉默信息调节因子(sirtuin)包括SIRT3、SIRT4和SIRT5,在细胞寿命、细胞凋亡、基因组稳定性和代谢等进程中发挥重要的作用。SIRT3、SIRT4和SIRT5参与保护应激状态下线粒体的完整性,维持其能量代谢,调节脑内神经递质受体、神经营养因子、细胞外基质蛋白及各种转录调节因子表达,在遗传或获得性癫痫的发生发展中起重要作用。本文回顾了近年来线粒体sirtuin家族在癫痫发病机制中的研究进展,同时针对以线粒体sirtuin为治疗靶点的相关问题进行总结并展望,为进一步研究线粒体sirtuin功能和临床应用提供依据。


关键词: 线粒体,  沉默信息调节因子,  癫痫,  氧化应激,  机制,  综述 
[1]   KHANA U, AKRAMM, DANIYALM, et al.Awareness and current knowledge of epilepsy[J]Metab Brain Dis, 2020, 35( 1): 45-63.
doi: 10.1007/s11011-019-00494-1
[2]   TERRONEG, BALOSSOS, PAULETTIA, et al.Inflammation and reactive oxygen species as disease modifiers in epilepsy[J]Neuropharmacology, 2020, 107742.
doi: 10.1016/j.neuropharm.2019.107742
[3]   L?SCHERW, POTSCHKAH, SISODIYAS M, et al.Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options[J]Pharmacol Rev, 2020, 72( 3): 606-638.
doi: 10.1124/pr.120.019539
[4]   MANFORDM. Recent advances in epilepsy[J]J Neurol, 2017, 264( 8): 1811-1824.
doi: 10.1007/s00415-017-8394-2
[5]   PEARSON-SMITHJ N, PATELM. Metabolic dysfunction and oxidative stress in epilepsy[J]Int J Mol Sci, 2017, 18( 11): 2365.
doi: 10.3390/ijms18112365
[6]   SHEKH-AHMADT, KOVACS, ABRAMOVA Y, et al.Reactive oxygen species in status epilepticus[J]Epilepsy Behav, 2019, 106410.
doi: 10.1016/j.yebeh.2019.07.011
[7]   SHEKH-AHMADT, LIEBA, KOVACS, et al.Combination antioxidant therapy prevents epileptogenesis and modifies chronic epilepsy[J]Redox Biol, 2019, 101278.
doi: 10.1016/j.redox.2019.101278
[8]   FRYDZI?SKAZ, OWCZAREKA, WINIARSKAK. Sirtuins and their role in metabolism regulation[J]Postepy Biochem, 2019, 65( 1): 31-40.
doi: 10.18388/pb.2019_254
[9]   SINGHC K, CHHABRAG, NDIAYEM A, et al.The role of sirtuins in antioxidant and redox signaling[J]Antioxidants Redox Signal, 2018, 28( 8): 643-661.
doi: 10.1089/ars.2017.7290
[10]   ANAMIKA, KHANNAA, ACHARJEEP, et al.Mitochondrial SIRT3 and neurodegenerative brain disorders[J]J Chem Neuroanatomy, 2019, 43-53.
doi: 10.1016/j.jchemneu.2017.11.009
[11]   RAHMANS. Mitochondrial diseases and status epilepticus[J]Epilepsia, 2018, 70-77.
doi: 10.1111/epi.14485
[12]   WANGS, ZHANGJ, DENGX, et al.Advances in characterization of SIRT3 deacetylation targets in mitochondrial function[J]Biochimie, 2020, 1-13.
doi: 10.1016/j.biochi.2020.08.021
[13]   CARRICOC, MEYERJ G, HEW, et al.The mitochondrial acylome emerges: proteomics, regulation by sirtuins, and metabolic and disease implications[J]Cell Metab, 2018, 27( 3): 497-512.
doi: 10.1016/j.cmet.2018.01.016
[14]   SOLE M, WAGNERS A, WEINERTB T, et al.Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase Sirt3[J/OL]PLoS ONE, 2012, 7( 12): e50545.
doi: 10.1371/journal.pone.0050545
[15]   HALLOWSW C, YUW, SMITHB C, et al.Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction[J]Mol Cell, 2011, 41( 2): 139-149.
doi: 10.1016/j.molcel.2011.01.002
[16]   WUG, LIUJ, LIS, et al.Glycyrrhizic acid protects juvenile epileptic rats against hippocampal damage through activation of Sirtuin3[J]Brain Res Bull, 2020, 98-106.
doi: 10.1016/j.brainresbull.2020.08.008
[17]   GANOL B, LIANGL P, RYANK, et al.Altered mitochondrial acetylation profiles in a kainic acid model of temporal lobe epilepsy[J]Free Radical Biol Med, 2018, 116-124.
doi: 10.1016/j.freeradbiomed.2018.05.063
[18]   CHOI, JEONGK H, ZHUJ, et al.Sirtuin3 protected against neuronal damage and cycled into nucleus in status epilepticus model[J]Mol Neurobiol, 2019, 56( 7): 4894-4903.
doi: 10.1007/s12035-018-1399-8
[19]   CHENGA, YANGY, ZHOUY, et al.Mitochondrial SIRT3 mediates adaptive responses of neurons to exercise and metabolic and excitatory challenges[J]Cell Metab, 2016, 23( 1): 128-142.
doi: 10.1016/j.cmet.2015.10.013
[20]   CHENGA, WANGJ, GHENAN, et al.SIRT3 haploinsufficiency aggravates loss of GABAergic interneurons and neuronal network hyperexcitability in an alzheimer’s disease model[J]J Neurosci, 2020, 40( 3): 694-709.
doi: 10.1523/JNEUROSCI.1446-19.2019
[21]   DIKALOVAA E, ITANIH A, NAZAREWICZR R, et al.Sirt3 impairment and SOD2 hyperacetylation in vascular oxidative stress and hypertension[J]Circ Res, 2017, 121( 5): 564-574.
doi: 10.1161/CIRCRESAHA.117.310933
[22]   SHUKLAS, SHARMAA, PANDEYV K, et al.Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells[J]Toxicol Appl Pharmacol, 2016, 70-83.
doi: 10.1016/j.taap.2015.12.006
[23]   YINJ, NIELSENM, CARCIONET, et al.Apolipoprotein E regulates mitochondrial function through the PGC-1α-sirtuin 3 pathway[J]Aging, 2019, 11( 23): 11148-11156.
doi: 10.18632/aging.102516
[24]   HASAN-OLIVEM M, LAURITZENK H, ALIM, et al.A ketogenic diet improves mitochondrial biogenesis and bioenergetics via the PGC1α-SIRT3-UCP2 axis[J]Neurochem Res, 2019, 44( 1): 22-37.
doi: 10.1007/s11064-018-2588-6
[25]   HANY, ZHOUS, COETZEES, et al.SIRT4 and its roles in energy and redox metabolism in health, disease and during exercise[J]Front Physiol, 2019, 1006.
doi: 10.3389/fphys.2019.01006
[26]   LIY, ZHOUY, WANGF, et al.SIRT4 is the last puzzle of mitochondrial sirtuins[J]BioOrg Med Chem, 2018, 26( 14): 3861-3865.
doi: 10.1016/j.bmc.2018.07.031
[27]   SASAKIY. Metabolic aspects of neuronal degeneration: From a NAD+ point of view[J]Neurosci Res, 2019, 9-20.
doi: 10.1016/j.neures.2018.07.001
[28]   SHIHJ, LIUL, MASONA, et al.Loss of SIRT4 decreases GLT-1-dependent glutamate uptake and increases sensitivity to kainic acid[J]J Neurochem, 2014, 131( 5): 573-581.
doi: 10.1111/jnc.12942
[29]   BRINGMAN-RODENBARGERL R, GUOA H, LYSSIOTISC A, et al.Emerging roles for SIRT5 in metabolism and cancer[J]Antioxidants Redox Signal, 2018, 28( 8): 677-690.
doi: 10.1089/ars.2017.7264
[30]   DUY, HUH, HUAC, et al.Tissue distribution, subcellular localization, and enzymatic activity analysis of human SIRT5 isoforms[J]Biochem BioPhys Res Commun, 2018, 503( 2): 763-769.
doi: 10.1016/j.bbrc.2018.06.073
[31]   KUMARS, LOMBARDD B. Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology[J]Crit Rev Biochem Mol Biol, 2018, 53( 3): 311-334.
doi: 10.1080/10409238.2018.1458071
[32]   JESKOH, WENCELP, STROSZNAJDERR P, et al.Sirtuins and their roles in brain aging and neurodegenerative disorders[J]Neurochem Res, 2017, 42( 3): 876-890.
doi: 10.1007/s11064-016-2110-y
[33]   NAKAGAWAT, LOMBD J, HAIGISM C, et al.SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle[J]Cell, 2009, 137( 3): 560-570.
doi: 10.1016/j.cell.2009.02.026
[34]   POLLETTAL, VERNUCCIE, CARNEVALEI, et al.SIRT5 regulation of ammonia-induced autophagy and mitophagy[J]Autophagy, 2015, 11( 2): 253-270.
doi: 10.1080/15548627.2015.1009778
[35]   KORONOWSKIK B, KHOURYN, MORRIS-BLANCOK C, et al.Metabolomics based identification of SIRT5 and protein kinase C epsilon regulated pathways in brain[J]Front Neurosci, 2018, 32.
doi: 10.3389/fnins.2018.00032
[36]   LUK, ZIMMERMANNM, G?RGB, et al.Hepatic encephalopathy is linked to alterations of autophagic flux in astrocytes[J]EBioMedicine, 2019, 539-553.
doi: 10.1016/j.ebiom.2019.09.058
[37]   EID T, GRUENBAUM S E, DHAHER R, et al. The glutamate-glutamine cycle in epilepsy[J]. Adv Neurobiol, 2016, 13: 351-400
[38]   LIF, LIUL. SIRT5 deficiency enhances susceptibility to kainate-induced seizures and exacerbates hippocampal neurodegeneration not through mitochondrial antioxidant enzyme SOD2[J]Front Cell Neurosci, 2016, 171.
doi: 10.3389/fncel.2016.00171
[39]   NIKOLICL, NOBILIP, SHENW, et al.Role of astrocyte purinergic signaling in epilepsy[J]Glia, 2020, 68( 9): 1677-1691.
doi: 10.1002/glia.23747
[40]   WANGC H, WEIY H. Roles of mitochondrial sirtuins in mitochondrial function, redox homeostasis, insulin resistance and type 2 diabetes[J]Int J Mol Sci, 2020, 21( 15): 5266.
doi: 10.3390/ijms21155266
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