线粒体自噬机制、相关疾病及中药对其调节作用的研究进展
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摘要
目的:了解线粒体自噬机制、相关疾病及中药(包括活性部位/成分)对其调节作用的研究进展,为促进中药药效物质挖掘、药理作用和机制研究以及创新中药研发等提供参考。方法:以"线粒体自噬""机制""疾病""中药""部位""成分""Mitophagy""Mechanism""Diseases""Traditional Chinese medicines""Herbal medicines""Site""Component"等为关键词,组合查询中国知网、万方、维普、PubMed、ScienceDirect、SpringerLink、Web of Science等数据库收录的相关文献,检索时限均为各数据库建库起至2018年5月,就线粒体自噬的分子机制、相关疾病及中药(包括活性部位/成分)对其调节作用的研究进展进行汇总与分析。结果与结论:共检索到相关文献1 925篇,其中有效文献54篇。线粒体自噬的调控主要由PTEN诱导激酶1(Pink1)/E3泛素连接酶Parkin、Nix/BNIP3、Mieap、FUN14结构域包含蛋白1(FUNDC1)、腺苷酸活化蛋白激酶(AMPK)、UNC-51样激酶1(ULK1)、高迁移率族蛋白B1(HMGB1)等蛋白介导,其功能异常可能会导致神经退行性疾病(阿尔茨海默病、帕金森病、肌萎缩性侧索硬化等)、肿瘤、心脏疾病(心肌缺血、心肌梗死等)、肝脏疾病(非酒精性脂肪肝、酒精性脂肪肝、肝损伤等)、代谢性疾病(胰岛素抵抗、尼曼匹克氏病等)的发生。部分中药活性部位/成分(三七总皂苷、槲皮素、白藜芦醇、姜黄素、褐藻素等)可通过激活AMPK、抑制Pink1/Parkin途径、增强Beclin1的表达等方式来调节线粒体自噬。深入研究中药对线粒体自噬的调节作用,有助于为揭示中药发挥药效作用的物质基础及本质、提高新药研发与临床治疗水平提供参考。
引文
[1]GATICA D,LAHIRI V,KLIONSKY DJ. Cargo recognition and degradation by selective autophagy[J]. Nat Cell Biol,2018,20(3):233-242.
[2]刘洹洹,王志舒,谭晓荣.线粒体自噬与人类疾病[J].中国生物化学与分子生物学报,2015,31(5):466-472.
[3]HARPER JW,ORDUREAU A,HEO JM. Building and decoding ubiquitin chains for mitophagy[J]. Cell Biol,2018,19(2):93-108.
[4]汤友静,牛玉娜,王辉. Pink1/Parkin介导的线粒体自噬分子机制[J].中国细胞生物学学报,2017,39(7):939-946.
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[6]奚慎立,卢克峰,张令强,等.泛素连接酶Smurf1与接头蛋白TRAF1相互作用并介导其泛素化降解[J].军事医学科学院院刊,2010,34(6):501-504.
[7]ORVEDAHL A,SUMPTER R JR,XIAO G,et al. Imagebased genome-wide siRNA screen identifies selective autophagy factors[J]. Nature,2011,480(7375):113-117.
[8]NOVAK I,KIRKIN V,MCEWAN DG,et al. Nix is a selective autophagy receptor for mitochondrial clearance[J].EMBO Rep,2010,11(1):45-51.
[9]SANDOVAL H,THIAGARAJAN P,DASGUPTA SK,et al. Essential role for Nix in autophagic maturation of erythroid cells[J]. Nature,2008,454(7201):232-235.
[10]ZHU Y,MASSEN S,TERENZIO M,et al. Modulation of serines 17 and 24 in the LC3-interacting region of BNIP3determines pro-survival mitophagy versus apoptosis[J]. J Biol Chem,2013,288(2):1099-1113.
[11]KITAMURA N,NAKAMURA Y,MIYAMOTO Y,et al.Mieap:a p53-inducible protein,controls mitochondrial quality by repairing or eliminating unhealthy mitochondria[J]. PLoS One,2011,6(1):e16060.
[12]王建东,张红,刘湧.线粒体自噬分子机制的研究进展[J].实用医学杂志,2011,27(17):3243-3245.
[13]史霄雨,于亮,王祯. FUNDC1与运动诱导线粒体自噬[J].生理科学进展,2017,48(5):388-392.
[14]WU W,TIAN W,HU Z,et al. ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy[J]. EMBO Rep,2014,15(5):566-575.
[15]EGAN DF,SHACKELFORD DB,MIHAYLOVA MM,et al. Phosphorylation of ULK1(HATG1)by AMP activated protein kinase connects energy sensing to mitophagy[J]. Science,2011,331(6016):456-461.
[16]PAULY M,DAUSSIN F,BURELLE Y,et al. AMPK activation stimulates autophagy and ameliorates muscular dystrophy in the mdx mouse diaphragm[J]. Am J Pathol,2012,181(2):583-592.
[17]BEHRENDS C,SOWA ME,GYGI SP,et al. Network organization of the human autophagy system[J]. Nature,2010,466(7302):68-76.
[18]RUSSELL RC,TIAN Y,YUAN H,et al. ULK1 induces autophagy byphosphorylating Beclin-1 and activating VPS34 lipid kinase[J]. Nat Cell Biol,2013,15(7):741-750.
[19]刘心怡,吴佳捷.高迁移率族蛋白B1基因沉默抑制子宫内膜癌侵袭与转移的机制[J].中南大学学报(医学版),2016,41(3):251-257.
[20]HUANG J,NI J,LIU K,et al. HMGB1 promotes drug resistance in osteosarcoma[J]. Cancer Res,2012,72(1):230-238.
[21]马文科,戴舒惠,罗鹏,等.线粒体自噬的研究进展[J].现代生物医学进展,2017,17(6):1176-1179.
[22]LEMASTERS JJ. Selective mitochondrial autophagy,or mitophagy,as a targeted defense against oxidative stress,mitochondrial dysfunction,and aging[J]. Rejuvenation Res,2005,8(1):3-5.
[23]MOREIRA PI,SIEDLAK SL,WANG XL,et al. Increased autophagic degradation of mitochondria in Alzheimer disease[J]. Autophagy,2017,3(6):614-615.
[24]王英,张强,乐卫东.线粒体自噬参与帕金森病发病机制的研究进展[J].中华临床医师杂志,2015,9(21):3962-3968.
[25]SMITH EF,SHAW PJ,DE VOS KJ. The role of mitochondria in amyotrophic lateral sclerosis[J]. Neurosci Lett,2017. DOI:10.1016/j.neulet.2017.06.052.
[26]MAZURE NM,BRAHIMI-HORN MC,POUYSSéGUR J. Hypoxic mitochondria:accomplices in resistance[J].Bull Cancer,2011,98(5):40-46.
[27]DUAN HY,LI YQ,YAN LJ,et al. Rcan1-1L overexpression induces mitochondrial autophagy and improves cell survival in angiotensinⅡ-exposed cardiomyocytes[J].Exp Cell Res,2015,335(1):99-106.
[28]李相迁. PINK1介导的线粒体自噬障碍在NASH发病机制中的作用[D].石家庄:河北医科大学,2017.
[29]WEI X,QI Y,ZHANG X,et al. Cadmium induces mitophagy through ROS-mediated PINK1/Parkin pathway[J].Toxicol Mech Methods,2014,24(7):504-511.
[30]KEANE PC,KURZAWA M,BLAIN PG,et al. Mitochondrial dysfunction in Parkinson’s disease[J]. Parkinsons Dis,2011. DOI:10.4061/2011/716871.
[31]赵鹏,孙亚平,陈红,等.阿尔茨海默病发病机制探究[J].中风与神经疾病杂志,2016,33(1):86-89.
[32]赵雪莲,于君,谢兆宏,等.线粒体自噬在阿尔茨海默病细胞模型中的作用机制[J].山东大学学报(医学版),2015,53(10):1-5.
[33]MOON HE,PAEK SH. Mitochondrial dysfunction in Parkinson’s disease[J]. Exp Neurobiol,2015. DOI:10.5607/en.2015.24.2.103.
[34]ROGERS RS,TUNGTUR S,TANAKA T,et al. Impaired mitophagy plays a role in denervation of neuromuscular junctions in ALS mice[J]. Front Neurosci,2017. DOI:10.3389/fnins.2017.00473.
[35]DING WX. Role of autophagy in liver physiology and pathophysiology[J]. World J Biol Chem,2010,1(1):3-12.
[36]MATHEW R,KARANTZA-WADSWORTH V,WHITE E. Role of autophagy in cancer[J]. Nat Rev Cancer,2007,7(12):961-967.
[37]KANAMORI H,TAKEMURA G,GOTO K,et al. Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion[J]. Am J Physiol Heart Circ Physiol,2011,300(6):2261-2271.
[38]班努·库肯,钟小兰,严金龙.大鼠心肌梗死后心脏线粒体及自噬小体的变化与Parkin蛋白活性的相关性[J].临床心血管病杂志,2016,32(6):598-602.
[39]KUBLI DA,ZHANG X,LEE Y,et al. Parkin protein deficiency exacerbates cardiac injuryand reduces survival following myocardial infarction[J]. J Biol Chem,2013,288(2):915-926.
[40]杨风丽.基于Pink1/Parkin信号通路研究白藜芦醇在酒精性脂肪肝中的线粒体自噬作用[D].合肥:安徽医科大学,2017.
[41]WILLIAMS JA,NI HM,HAYNES A,et al. Chronic deletion and acute knockdown of Parkin have differential responses to acetaminophen-induced mitophagy and liver injury in mice[J]. J Biol Chem,2015,290(17):10934-10946.
[42]DUGAIL I,KALOPISSIS A,MIQUEL M,et al. Lipids in metabolic diseases[J]. Biochimie,2014. DOI:10.1016/j.biochi.2013.11.009.
[43]时丽丽,张莉,谭初兵,等.线粒体功能损伤与胰岛素抵抗[J].中国药理学通报,2012,28(11):1481-1486.
[44]BONNARD C,DURAND A,PEYROL S,et al. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice[J]. J Clin Invest,2008,118(2):789-800.
[45]刘丹慧,吕建新.线粒体自噬的研究进展[J].细胞生物学杂志,2008,30(4):467-471.
[46]ORDONEZ MP. Defective mitophagy in human NiemannPick Type C1 neurons is due to abnormal autophagy activation[J]. Autophagy,2012,8(7):1157-1158.
[47]周金玲,杨玉芳,黄振光,等.三七总皂苷通过HIF-1α/BNIP3途径增强线粒体自噬保护大鼠顺铂肾损伤[J].中国药学杂志,2017,52(3):196-200.
[48]张怀念,曹治家,陈红梅,等.木犀草素对肝癌HepG2细胞线粒体自噬及Bcl-2表达的影响[J].广东医学,2015,36(23):3386-3390.
[49]GIBELLINI L,BIANCHINI E,DE BIASI S,et al. Natural compounds modulating mitochondrial functions[J]. Evid Based Complement Alternat Med,2015. DOI:10.1155/2015/527209.
[50]廖政邦,李明,谢松强.褐藻素诱导肝癌HepG2细胞凋亡和自噬的机制[J].中国实验方剂学杂志,2014,20(15):181-184.
[51]WANG X,LEUNG AW,LUO J,et al. TEM observation of ultrasound induced mitophagy in nasopharyngeal carcinoma cells in the presence of curcumin[J]. Exp Ther Med,2012,3(1):146-148.
[52]莫媛媛,侯华新,黎丹戎,等.大黄素乙酰化物致鼻咽癌CNE-1细胞线粒体自噬活性的研究[J].中国癌症防治杂志,2014,6(1):1-6.
[53]尤付玲.远志皂苷调节线粒体自噬在抗Aβ诱导细胞损伤中的作用及机制[D].广州:广东药科大学,2017.
[54]陈俊莉.阿魏酸通过诱导线粒体自噬保护糖氧剥夺引起的内皮细胞损伤[D].广州:广州中医药大学,2016.
[2]刘洹洹,王志舒,谭晓荣.线粒体自噬与人类疾病[J].中国生物化学与分子生物学报,2015,31(5):466-472.
[3]HARPER JW,ORDUREAU A,HEO JM. Building and decoding ubiquitin chains for mitophagy[J]. Cell Biol,2018,19(2):93-108.
[4]汤友静,牛玉娜,王辉. Pink1/Parkin介导的线粒体自噬分子机制[J].中国细胞生物学学报,2017,39(7):939-946.
[5]张盼. PINK1/Parkin介导的线粒体自噬在溃疡性结肠炎发病中的作用[D].石家庄:河北医科大学,2016.
[6]奚慎立,卢克峰,张令强,等.泛素连接酶Smurf1与接头蛋白TRAF1相互作用并介导其泛素化降解[J].军事医学科学院院刊,2010,34(6):501-504.
[7]ORVEDAHL A,SUMPTER R JR,XIAO G,et al. Imagebased genome-wide siRNA screen identifies selective autophagy factors[J]. Nature,2011,480(7375):113-117.
[8]NOVAK I,KIRKIN V,MCEWAN DG,et al. Nix is a selective autophagy receptor for mitochondrial clearance[J].EMBO Rep,2010,11(1):45-51.
[9]SANDOVAL H,THIAGARAJAN P,DASGUPTA SK,et al. Essential role for Nix in autophagic maturation of erythroid cells[J]. Nature,2008,454(7201):232-235.
[10]ZHU Y,MASSEN S,TERENZIO M,et al. Modulation of serines 17 and 24 in the LC3-interacting region of BNIP3determines pro-survival mitophagy versus apoptosis[J]. J Biol Chem,2013,288(2):1099-1113.
[11]KITAMURA N,NAKAMURA Y,MIYAMOTO Y,et al.Mieap:a p53-inducible protein,controls mitochondrial quality by repairing or eliminating unhealthy mitochondria[J]. PLoS One,2011,6(1):e16060.
[12]王建东,张红,刘湧.线粒体自噬分子机制的研究进展[J].实用医学杂志,2011,27(17):3243-3245.
[13]史霄雨,于亮,王祯. FUNDC1与运动诱导线粒体自噬[J].生理科学进展,2017,48(5):388-392.
[14]WU W,TIAN W,HU Z,et al. ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy[J]. EMBO Rep,2014,15(5):566-575.
[15]EGAN DF,SHACKELFORD DB,MIHAYLOVA MM,et al. Phosphorylation of ULK1(HATG1)by AMP activated protein kinase connects energy sensing to mitophagy[J]. Science,2011,331(6016):456-461.
[16]PAULY M,DAUSSIN F,BURELLE Y,et al. AMPK activation stimulates autophagy and ameliorates muscular dystrophy in the mdx mouse diaphragm[J]. Am J Pathol,2012,181(2):583-592.
[17]BEHRENDS C,SOWA ME,GYGI SP,et al. Network organization of the human autophagy system[J]. Nature,2010,466(7302):68-76.
[18]RUSSELL RC,TIAN Y,YUAN H,et al. ULK1 induces autophagy byphosphorylating Beclin-1 and activating VPS34 lipid kinase[J]. Nat Cell Biol,2013,15(7):741-750.
[19]刘心怡,吴佳捷.高迁移率族蛋白B1基因沉默抑制子宫内膜癌侵袭与转移的机制[J].中南大学学报(医学版),2016,41(3):251-257.
[20]HUANG J,NI J,LIU K,et al. HMGB1 promotes drug resistance in osteosarcoma[J]. Cancer Res,2012,72(1):230-238.
[21]马文科,戴舒惠,罗鹏,等.线粒体自噬的研究进展[J].现代生物医学进展,2017,17(6):1176-1179.
[22]LEMASTERS JJ. Selective mitochondrial autophagy,or mitophagy,as a targeted defense against oxidative stress,mitochondrial dysfunction,and aging[J]. Rejuvenation Res,2005,8(1):3-5.
[23]MOREIRA PI,SIEDLAK SL,WANG XL,et al. Increased autophagic degradation of mitochondria in Alzheimer disease[J]. Autophagy,2017,3(6):614-615.
[24]王英,张强,乐卫东.线粒体自噬参与帕金森病发病机制的研究进展[J].中华临床医师杂志,2015,9(21):3962-3968.
[25]SMITH EF,SHAW PJ,DE VOS KJ. The role of mitochondria in amyotrophic lateral sclerosis[J]. Neurosci Lett,2017. DOI:10.1016/j.neulet.2017.06.052.
[26]MAZURE NM,BRAHIMI-HORN MC,POUYSSéGUR J. Hypoxic mitochondria:accomplices in resistance[J].Bull Cancer,2011,98(5):40-46.
[27]DUAN HY,LI YQ,YAN LJ,et al. Rcan1-1L overexpression induces mitochondrial autophagy and improves cell survival in angiotensinⅡ-exposed cardiomyocytes[J].Exp Cell Res,2015,335(1):99-106.
[28]李相迁. PINK1介导的线粒体自噬障碍在NASH发病机制中的作用[D].石家庄:河北医科大学,2017.
[29]WEI X,QI Y,ZHANG X,et al. Cadmium induces mitophagy through ROS-mediated PINK1/Parkin pathway[J].Toxicol Mech Methods,2014,24(7):504-511.
[30]KEANE PC,KURZAWA M,BLAIN PG,et al. Mitochondrial dysfunction in Parkinson’s disease[J]. Parkinsons Dis,2011. DOI:10.4061/2011/716871.
[31]赵鹏,孙亚平,陈红,等.阿尔茨海默病发病机制探究[J].中风与神经疾病杂志,2016,33(1):86-89.
[32]赵雪莲,于君,谢兆宏,等.线粒体自噬在阿尔茨海默病细胞模型中的作用机制[J].山东大学学报(医学版),2015,53(10):1-5.
[33]MOON HE,PAEK SH. Mitochondrial dysfunction in Parkinson’s disease[J]. Exp Neurobiol,2015. DOI:10.5607/en.2015.24.2.103.
[34]ROGERS RS,TUNGTUR S,TANAKA T,et al. Impaired mitophagy plays a role in denervation of neuromuscular junctions in ALS mice[J]. Front Neurosci,2017. DOI:10.3389/fnins.2017.00473.
[35]DING WX. Role of autophagy in liver physiology and pathophysiology[J]. World J Biol Chem,2010,1(1):3-12.
[36]MATHEW R,KARANTZA-WADSWORTH V,WHITE E. Role of autophagy in cancer[J]. Nat Rev Cancer,2007,7(12):961-967.
[37]KANAMORI H,TAKEMURA G,GOTO K,et al. Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion[J]. Am J Physiol Heart Circ Physiol,2011,300(6):2261-2271.
[38]班努·库肯,钟小兰,严金龙.大鼠心肌梗死后心脏线粒体及自噬小体的变化与Parkin蛋白活性的相关性[J].临床心血管病杂志,2016,32(6):598-602.
[39]KUBLI DA,ZHANG X,LEE Y,et al. Parkin protein deficiency exacerbates cardiac injuryand reduces survival following myocardial infarction[J]. J Biol Chem,2013,288(2):915-926.
[40]杨风丽.基于Pink1/Parkin信号通路研究白藜芦醇在酒精性脂肪肝中的线粒体自噬作用[D].合肥:安徽医科大学,2017.
[41]WILLIAMS JA,NI HM,HAYNES A,et al. Chronic deletion and acute knockdown of Parkin have differential responses to acetaminophen-induced mitophagy and liver injury in mice[J]. J Biol Chem,2015,290(17):10934-10946.
[42]DUGAIL I,KALOPISSIS A,MIQUEL M,et al. Lipids in metabolic diseases[J]. Biochimie,2014. DOI:10.1016/j.biochi.2013.11.009.
[43]时丽丽,张莉,谭初兵,等.线粒体功能损伤与胰岛素抵抗[J].中国药理学通报,2012,28(11):1481-1486.
[44]BONNARD C,DURAND A,PEYROL S,et al. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice[J]. J Clin Invest,2008,118(2):789-800.
[45]刘丹慧,吕建新.线粒体自噬的研究进展[J].细胞生物学杂志,2008,30(4):467-471.
[46]ORDONEZ MP. Defective mitophagy in human NiemannPick Type C1 neurons is due to abnormal autophagy activation[J]. Autophagy,2012,8(7):1157-1158.
[47]周金玲,杨玉芳,黄振光,等.三七总皂苷通过HIF-1α/BNIP3途径增强线粒体自噬保护大鼠顺铂肾损伤[J].中国药学杂志,2017,52(3):196-200.
[48]张怀念,曹治家,陈红梅,等.木犀草素对肝癌HepG2细胞线粒体自噬及Bcl-2表达的影响[J].广东医学,2015,36(23):3386-3390.
[49]GIBELLINI L,BIANCHINI E,DE BIASI S,et al. Natural compounds modulating mitochondrial functions[J]. Evid Based Complement Alternat Med,2015. DOI:10.1155/2015/527209.
[50]廖政邦,李明,谢松强.褐藻素诱导肝癌HepG2细胞凋亡和自噬的机制[J].中国实验方剂学杂志,2014,20(15):181-184.
[51]WANG X,LEUNG AW,LUO J,et al. TEM observation of ultrasound induced mitophagy in nasopharyngeal carcinoma cells in the presence of curcumin[J]. Exp Ther Med,2012,3(1):146-148.
[52]莫媛媛,侯华新,黎丹戎,等.大黄素乙酰化物致鼻咽癌CNE-1细胞线粒体自噬活性的研究[J].中国癌症防治杂志,2014,6(1):1-6.
[53]尤付玲.远志皂苷调节线粒体自噬在抗Aβ诱导细胞损伤中的作用及机制[D].广州:广东药科大学,2017.
[54]陈俊莉.阿魏酸通过诱导线粒体自噬保护糖氧剥夺引起的内皮细胞损伤[D].广州:广州中医药大学,2016.