线粒体相关的细胞信号分子与心血管疾病
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摘要
线粒体上与心血管疾病相关的位点突变(mtDNA突变)是心血管疾病发病的分子机制之一。线粒体的代谢与线粒体活性氧簇(mROS)、钙离子、一氧化氮、激素等信号分子相关。这些信号分子的变化,如mROS增加、ATP减少等,影响线粒体及细胞功能,进而引发相关生物应激反应,最终导致心血管相关疾病。现讨论线粒体相关的信号分子参与转录、细胞凋亡与自噬、血管紧张和炎症等活动的过程,并详细介绍线粒体相关的信号分子与心血管疾病(着重介绍高血压和冠心病)之间的关系。
Mitochondrial DNA(mt DNA) mutation is one of the molecular mechanisms of cardiovascular diseases. mt DNA mutations affect mitochondrial metabolism which are associated with m ROS, calcium, nitric oxide, hormones as well as other related signaling molecules. These signaling molecules such as m ROS affect ATP production and change mitochondrial and cellular function, which causes bio-stress response, and ultimately may lead to cardiovascular diseases. This article reviewed mitochondrial signaling molecules involved in transcription, apoptosis, autophagy, vascular tension, inflammation, etc. as well as the relationship between mit=ochondrial signaling molecules and cardiovascular diseases(mainly coronary atherosclerotic heart disease and hypertension).
Mitochondrial DNA(mt DNA) mutation is one of the molecular mechanisms of cardiovascular diseases. mt DNA mutations affect mitochondrial metabolism which are associated with m ROS, calcium, nitric oxide, hormones as well as other related signaling molecules. These signaling molecules such as m ROS affect ATP production and change mitochondrial and cellular function, which causes bio-stress response, and ultimately may lead to cardiovascular diseases. This article reviewed mitochondrial signaling molecules involved in transcription, apoptosis, autophagy, vascular tension, inflammation, etc. as well as the relationship between mit=ochondrial signaling molecules and cardiovascular diseases(mainly coronary atherosclerotic heart disease and hypertension).
引文
[1]Drompari P,Michelakis ED,Mitochondria in vascular health and disease.Annu Rev Physiol,2013,75:95-126
[2]Niemann B,Rohrbach S,Miller MR,et al.Oxidative stress and cardiovascular risk:obesity,diabetes,smoking,and pollution:part 3 of a 3-part series.J Am Coll Cardiol,2017,70:230-51
[3]Starkov AA.The role of mitochondria in reactive oxygen species metabolism and signaling.Ann N Y Acad Sci,2008,1147:37-52
[4]Samhanarias AK,Gutierrezmerino C.Purified NADHcytochrome b5 reductase is a novel superoxide anion source inhibited by apocynin:sensitivity to nitric oxide and peroxynitrite.Free Rad Biol Med,2014,73:174-89
[5]Santin Y,Sicard P,Vigneron F,et al.Oxidative stress by monoamine oxidase-A impairs transcription factor-EB activation and autophagosome clearance leading to cardiomyocyte necrosis and heart failure.Antioxid Redox Signal,2016,25:10-7
[6]Kim YM,Kim SJ,Tatsunami R,et al.ROS-induced ROS release orchestrated by Nox4,Nox2 and mitochondria in VEGF signaling and angiogenesis.Am J Physiol Cell Physiol,2017,312:C749-64
[7]耿军伟,于涵,林枝,等.动物细胞中活性氧的生成及代谢.生命科学,2015,27:609-17
[8]郭云辉,陈凤江,吕红梅.线粒体相关内质网膜的钙信号.医学信息,2015,28:379
[9]Sch?nleitner P,Schotten U,Antoons G.Mechanosensitivity of microdomain calcium signalling in the heart.Prog Biophys Mol Biol,2017,130:288-301
[10]Nisoli E,Carruba MO.Nitric oxide and mitochondrial biogenesis.J Cell Sci,2006,119:2855-62
[11]曹茄柽,张崇高.一氧化氮可调控线粒体的生物形成.生理科学进展,2003,34:297
[12]宋绍辉,黄国雄,赵文,等.钙敏感受体与内源性一氧化氮在致大鼠高肺血流性肺动脉高压形成中的意义.微创医学,2013,8:256-8
[13]王晓健,厉朝龙.NO与细胞凋亡.国外医学:生理、病理科学与临床分册,2001,21:97-9
[14]Denton RM.Regulation of mitochondrial dehydrogenases by calcium ions.Biochim Biophys Acta,2009,1787:1309-16
[15]Papandreou I,Cairns RA,Fontana L,et al.HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption.Cell Metab,2006,3:187-97
[16]Nishikawa T,Edelstein D,Du XL,et al.Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.Nature,2000,404:787-90
[17]Cui Y,Xu X,Bi H,et al.Expression modification of uncoupling proteins and Mn SOD in retinal endothelial cells and pericytes induced by high glucose:the role of reactive oxygen species in diabetic retinopathy.Exp Eye Res,2006,83:807-16
[18]Lee KU,Lee IK,Han J,et al.Effects of recombinant adenovirus-mediated uncoupling protein 2 overexpression on endothelial function and apoptosis.Circ Res,2005,96:1200-7
[19]Injeong C,Jin HG,Hoon CJ.Uncoupling protein,UCP-4may be involved in neuronal defects during aging and resistance to pathogens in Caenorhabditis elegans.Mol Cell,2016,39:680-6
[20]Lentes KU,Tu N,Chen H,et al.Genomicorganization and mutational analysis of the human UCP2 gene,a prime candidate gene for human obesity.J Recept Signal Transduct Res,1999,19:229-44
[21]Wrutniak-Cabello C,Casas F,Cabello G.Thyroid hormone action in mitochondria.J Mol Endocrinol,2001,26:67-77
[22]Mancini A,Di Segni C,Raimondo S,et al.Thyroid hormones,oxidative stress,and inflammation.Med Inflamm,2016,2016:6757154
[23]Ye Q,Huang W,Li D,et al.Overexpression of PGC-1αinfluences mitochondrial signal transduction of dopaminergic neurons.Mol Neurobiol,2016,53:3756-70
[24]Michel S,Wanet A,De Pauw A,et al.Crosstalk between mitochondrial(dys)function and mitochondrial abundance.J Cell Physiol,2012,227:2297-310
[25]Ryan MT,Hoogenraad NJ.Mitochondrial-nuclear communications.Annu Rev Biochem,2007,76:701-22
[26]Zamzami N,Kroemer G.The mitochondrion in apoptosis:how Pandora’s box opens.Nat Rev Mol Cell Biol,2001,2:67-71
[27]Halestrap AP,Woodfield KY,Connern CP.Oxidative stress,thiol reagents,and membrane potential modulate the mitochondrial permeability transition by affecting nucleotide binding to the adenine nucleotide translocase.J Biol Chem,1997,272:3346-54
[28]Patwardhan GA,Beverly LJ,Siskind LJ.Sphingolipids and mitochondrial apoptosis.J Bioenerg Biomembr,2016,48:153-68
[29]Hailey DW,Rambold AS,Satpute-Krishnan P,et al.Mitochondria supply membranes for autophagosome biogenesis during starvation.Cell,2010,141:656-67
[30]Green DR,Galluzzi L,Kroemer G.Mitochondria and the autophagy-inflammation-cell death axis in organismal aging.Science,2011,333:1109-12
[31]Youle RJ,Narendra DP.Mechanisms of mitophagy.Nat Rev Mol Cell Biol,2011,12:9-14
[32]Prajapati P,Sripada L,Singh K,et al.Systemic analysis of mi RNAs in PD stress condition:mi R-5701 modulates mitochondrial-lysosomal cross talk to regulate neuronal death.Mol Neurobiol,2018,55:4689-701
[33]Zhou R,Yazdi AS,Menu P,et al.A role for mitochondria in NLRP3 inflammasome activation.Nature,2011,469:221-25
[34]Kepp O,Galluzzi L,Kroemer G.Mitochondrial control of the NLRP3 inflammasome.Nat Immunol,2011,12:199-200
[35]Ding Z,Liu S,Wang X,et al.LOX-1,mt DNA damage,and NLRP3 inflammasome activation in macrophages:implications in atherogenesis.Cardiovasc Res,2014,103:619-28
[36]Shimada K,Crother TR,Karlin J,et al.Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis.Immunity,2012,36:401-14
[37]Zhang Q,Raoof M,Chen Y,et al.Circulating mitochondrial DAMPs cause inflammatory responses to injury.Nature,2010,464:104-7
[38]Mabile L,Meilhac O,Escargueil-Blanc I,et al.Mitochondrial function is involved in LDL oxidation mediated by human cultured endothelial cells.Arterioscler Thromb Vasc Biol,1997,17:1575-82
[39]Landar A,Zmijewski JW,Dickinson DA,et al.Interaction of electrophilic lipid oxidation products with mitochondria in endothelial cells and formation of reactive oxygen species.Am J Physiol Heart Circ Physiol,2006,290:H1777-87
[40]Hessler JR,Robertson AL Jr,Chisolm GM 3rd.LDLinduced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture.Atherosclerosis,1979,32:213-29
[41]Chen J,Mehta JL,Haider N,et al.Role of caspases in OxLDL-induced apoptotic cascade in human coronary artery endothelial cells.Circ Res,2004,94:370-76
[42]Sato Y,Fujiwara H,Takatsu Y.Biochemical markers in heart failure.J Cardiol,2012,59:1-7
[43]王馨佩,刘振华.线粒体在肺动脉高压发生中的研究进展.医学研究生学报,2017,30:204-7
[44]刘晓鹏.新型经导管置入主动脉瓣膜临床前研究及线粒体自噬对动脉粥样硬化保护机制研究[D].北京:北京协和医学院中国医学科学院清华大学医学部,2016
[45]朱晓彤,李广平.线粒体功能障碍与心力衰竭的关系.中国心血管杂志,2016,21:65-8
[46]Razani B,Feng C,Coleman T,et al.Autophagy links inflammasomes to atherosclerotic progression.Cell Metab,2012,15:534-44
[47]Akazawa H,Komazaki S,Shimomura H,et al.Diphtheria toxin-induced autophagic cardiomyocyte death plays a pathogenic role in mouse model of heart failure.J Biol Chem,2004,279:41095-103
[48]Yu T,Robotham JL,Yoon Y.Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology.Proc Natl Acad Sci USA,2006,103:2653-58
[49]Shenouda SM,Widlansky ME,Chen K,et al.Altered mitochondrial dynamics contributes to endothelial dysfunction in diabetes mellitus.Circulation,2011,124:444-53
[50]Makino A,Scott BT,Dillmann WH.Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1diabetes.Diabetologia,2010,53:1783-94
[51]Boengler K,Kosiol M,Mayr M,et al.Mitochondria and ageing:role in heart,skeletal muscle and adipose tissue.J Cachexia Sarcopenia Muscle,2017,8:349-69
[52]Michelakis ED,Thebaud B,Weir EK,et al.Hypoxic pulmonary vasoconstriction:redox regulation of O2-sensitive K+channels by a mitochondrial O2-sensor in resistance artery smooth muscle cells.J Mol Cell Cardiol,2004,37:1119-36
[53]Weir EK,Lopez-Barneo J,Buckler KJ,et al.Acute oxygen-sensing mechanisms.N Engl J Med,2005,353:2042-55
[54]Jones G,Zhang H,Colman M.The effect of bioenergetic impairment of cytosolic processes in spatio-temporal Ca2+dynamics in a three-dimensional cardiomyocyte model[C].2016 Computing in Cardiology Conference
[55]Semenza GL.Oxygen sensing,homeostasis,and disease.N Engl J Med,2011,365:537-47
[56]Chen X,Zhang Y,Xu B,et al.The mitochondrial calcium uniporter is involved in mitochondrial calcium cycle dysfunction:underlying mechanism of hypertension associated with mitochondrial t RNAIle A4263G mutation.Int J Biochem Cell Biol,2016,78:307-14
[57]林枝,姜丰,王恒,等.一个携带线粒体DNA t RNALeu(UUR)3253T>C突变的中国汉族原发性高血压家系临床及遗传特征分析[C].浙江省医学遗传学学术年会暨高通量基因测序产前筛查与诊断技术研讨会,2015
[58]Xu M,He Y,Geng J,et al.The mitochondrial t RNAMet/t RNAGlnA4401G and t RNACysG5821A mutations may be associated with hypertension in two Han Chinese families.Hereditas,2014,36:127-34
[59]Wang S,Li R,Fettermann A,et al.Maternally inherited essential hypertension is associated with the novel4263A>G mutation in the mitochondrial t RNAIle gene in a large Han Chinese family.Circ Res,2011,108:862-70
[60]肖云.高血压相关的线粒体新突变t RNAAla T5655C的致病机理研究[D].杭州:浙江大学,2013
[61]刘浩.母系遗传2型糖尿病相关的线粒体t RNA突变及其功能研究[D].浙江大学,2016
[62]Liu H,Li R,Li W,et al.Maternally inherited diabetes is associated with a homoplasmic T10003C mutation in the mitochondrial t RNAGly gene.Mitochondrion,2015,21:49-57
[63]Meng W,Peng Y,Jing Z,et al.A deafness-associated t RNAAsp mutation alters the m1G37 modification,aminoacylation and stability of t RNAAsp and mitochondrial function.Nucleic Acids Res,2016,44:10974
[64]Li G,Yong Y,Rui B.Mitochondrial DNA mutation m.5512A>G in the acceptor-stem of mitochondrial t RNATrp,causing maternally inherited essential hypertension.Biochem Biophys Res Commun,2016,479:800-7
[65]Gomes LC,Di Benedetto G,Scorrano L.During autophagy mitochondria elongate,are spared from degradation and sustain cell viability.Nat Cell Biol,2011,13:589-98
[66]Toyama EQ,Herzig S,Courchet J,et al.Metabolism.AMP-activated protein kinase mediates mitochondrial fission in response to energy stress.Science,2016,351:275-81
[67]Anand R,Langer T,Baker MJ.Proteolytic control of mitochondrial function and morphogenesis.Biochim Biophys Acta,2013,1833:195-204
[68]Givvimani S,Pushpakumar S,Veeranki S,et al.Dysregulation of Mfn2 and Drp-1 proteins in heart failure.Can J Physiol Pharmacol,2014,92:583-91
[69]Yu T,Robotham JL,Yoon Y.Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology.Proc Natl Acad Sci USA,2006,103:2653-8
[70]Trudeau K,Molina AJ,Guo W,et al.High glucose disrupts mitochondrial morphology in retinal endothelial cells:implications for diabetic retinopathy.Am J Pathol,2010,177:447-55
[71]Ambros V.The functions of animal micro RNAs.Nature2004,43l:350-5
[72]Guttman M,Donaghey J,Carey BW,et al.linc RNAs act in the circuitry controlling pluripotency and differentiation.Nature,2011,477:295-300
[73]Ishii N,Ozaki K,Mizuno H,et al.Identification of a novel non-coding RNA,MIAT,that confers risk of myocardial infarction.J Hum Genet,2006,51:1087-99
[74]Batlevi Y,Spada AR.Mitochondrial autophagy in neural function,neurodegenerative disease,neuron cell death,and aging.Neurobiol Dis,2011,43:46-51
[75]Kanki T,Klionsky DJ,Koji O.Mitochondria autophagy in yeast.Antioxiod Redox Signal,2011,14:1989-2001
[76]Youle RJ,Narendra DP.Mechanism of mitophagy.Nat Rev Mol Cell Biol,2011,12:9-14
[77]Cui C,Chen S,Qiao J,et al.PINK1-Parkin alleviates metabolic stress induced by obesity in adipose tissue and in 3T3-L1 preadipocytes.Biochem Biophys Commun,2018,498:445-52
[78]Heeman B,Van den Haute C,Aelvoet SA,et al.Pink1depletion affects mitochondrial homeostasis.Movement Disorders,2010,25:S624
[79]Tan AS,Baty JW,Dong LF,et al.Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA.Cell Metabolism,2015,21:81-94
[2]Niemann B,Rohrbach S,Miller MR,et al.Oxidative stress and cardiovascular risk:obesity,diabetes,smoking,and pollution:part 3 of a 3-part series.J Am Coll Cardiol,2017,70:230-51
[3]Starkov AA.The role of mitochondria in reactive oxygen species metabolism and signaling.Ann N Y Acad Sci,2008,1147:37-52
[4]Samhanarias AK,Gutierrezmerino C.Purified NADHcytochrome b5 reductase is a novel superoxide anion source inhibited by apocynin:sensitivity to nitric oxide and peroxynitrite.Free Rad Biol Med,2014,73:174-89
[5]Santin Y,Sicard P,Vigneron F,et al.Oxidative stress by monoamine oxidase-A impairs transcription factor-EB activation and autophagosome clearance leading to cardiomyocyte necrosis and heart failure.Antioxid Redox Signal,2016,25:10-7
[6]Kim YM,Kim SJ,Tatsunami R,et al.ROS-induced ROS release orchestrated by Nox4,Nox2 and mitochondria in VEGF signaling and angiogenesis.Am J Physiol Cell Physiol,2017,312:C749-64
[7]耿军伟,于涵,林枝,等.动物细胞中活性氧的生成及代谢.生命科学,2015,27:609-17
[8]郭云辉,陈凤江,吕红梅.线粒体相关内质网膜的钙信号.医学信息,2015,28:379
[9]Sch?nleitner P,Schotten U,Antoons G.Mechanosensitivity of microdomain calcium signalling in the heart.Prog Biophys Mol Biol,2017,130:288-301
[10]Nisoli E,Carruba MO.Nitric oxide and mitochondrial biogenesis.J Cell Sci,2006,119:2855-62
[11]曹茄柽,张崇高.一氧化氮可调控线粒体的生物形成.生理科学进展,2003,34:297
[12]宋绍辉,黄国雄,赵文,等.钙敏感受体与内源性一氧化氮在致大鼠高肺血流性肺动脉高压形成中的意义.微创医学,2013,8:256-8
[13]王晓健,厉朝龙.NO与细胞凋亡.国外医学:生理、病理科学与临床分册,2001,21:97-9
[14]Denton RM.Regulation of mitochondrial dehydrogenases by calcium ions.Biochim Biophys Acta,2009,1787:1309-16
[15]Papandreou I,Cairns RA,Fontana L,et al.HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption.Cell Metab,2006,3:187-97
[16]Nishikawa T,Edelstein D,Du XL,et al.Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.Nature,2000,404:787-90
[17]Cui Y,Xu X,Bi H,et al.Expression modification of uncoupling proteins and Mn SOD in retinal endothelial cells and pericytes induced by high glucose:the role of reactive oxygen species in diabetic retinopathy.Exp Eye Res,2006,83:807-16
[18]Lee KU,Lee IK,Han J,et al.Effects of recombinant adenovirus-mediated uncoupling protein 2 overexpression on endothelial function and apoptosis.Circ Res,2005,96:1200-7
[19]Injeong C,Jin HG,Hoon CJ.Uncoupling protein,UCP-4may be involved in neuronal defects during aging and resistance to pathogens in Caenorhabditis elegans.Mol Cell,2016,39:680-6
[20]Lentes KU,Tu N,Chen H,et al.Genomicorganization and mutational analysis of the human UCP2 gene,a prime candidate gene for human obesity.J Recept Signal Transduct Res,1999,19:229-44
[21]Wrutniak-Cabello C,Casas F,Cabello G.Thyroid hormone action in mitochondria.J Mol Endocrinol,2001,26:67-77
[22]Mancini A,Di Segni C,Raimondo S,et al.Thyroid hormones,oxidative stress,and inflammation.Med Inflamm,2016,2016:6757154
[23]Ye Q,Huang W,Li D,et al.Overexpression of PGC-1αinfluences mitochondrial signal transduction of dopaminergic neurons.Mol Neurobiol,2016,53:3756-70
[24]Michel S,Wanet A,De Pauw A,et al.Crosstalk between mitochondrial(dys)function and mitochondrial abundance.J Cell Physiol,2012,227:2297-310
[25]Ryan MT,Hoogenraad NJ.Mitochondrial-nuclear communications.Annu Rev Biochem,2007,76:701-22
[26]Zamzami N,Kroemer G.The mitochondrion in apoptosis:how Pandora’s box opens.Nat Rev Mol Cell Biol,2001,2:67-71
[27]Halestrap AP,Woodfield KY,Connern CP.Oxidative stress,thiol reagents,and membrane potential modulate the mitochondrial permeability transition by affecting nucleotide binding to the adenine nucleotide translocase.J Biol Chem,1997,272:3346-54
[28]Patwardhan GA,Beverly LJ,Siskind LJ.Sphingolipids and mitochondrial apoptosis.J Bioenerg Biomembr,2016,48:153-68
[29]Hailey DW,Rambold AS,Satpute-Krishnan P,et al.Mitochondria supply membranes for autophagosome biogenesis during starvation.Cell,2010,141:656-67
[30]Green DR,Galluzzi L,Kroemer G.Mitochondria and the autophagy-inflammation-cell death axis in organismal aging.Science,2011,333:1109-12
[31]Youle RJ,Narendra DP.Mechanisms of mitophagy.Nat Rev Mol Cell Biol,2011,12:9-14
[32]Prajapati P,Sripada L,Singh K,et al.Systemic analysis of mi RNAs in PD stress condition:mi R-5701 modulates mitochondrial-lysosomal cross talk to regulate neuronal death.Mol Neurobiol,2018,55:4689-701
[33]Zhou R,Yazdi AS,Menu P,et al.A role for mitochondria in NLRP3 inflammasome activation.Nature,2011,469:221-25
[34]Kepp O,Galluzzi L,Kroemer G.Mitochondrial control of the NLRP3 inflammasome.Nat Immunol,2011,12:199-200
[35]Ding Z,Liu S,Wang X,et al.LOX-1,mt DNA damage,and NLRP3 inflammasome activation in macrophages:implications in atherogenesis.Cardiovasc Res,2014,103:619-28
[36]Shimada K,Crother TR,Karlin J,et al.Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis.Immunity,2012,36:401-14
[37]Zhang Q,Raoof M,Chen Y,et al.Circulating mitochondrial DAMPs cause inflammatory responses to injury.Nature,2010,464:104-7
[38]Mabile L,Meilhac O,Escargueil-Blanc I,et al.Mitochondrial function is involved in LDL oxidation mediated by human cultured endothelial cells.Arterioscler Thromb Vasc Biol,1997,17:1575-82
[39]Landar A,Zmijewski JW,Dickinson DA,et al.Interaction of electrophilic lipid oxidation products with mitochondria in endothelial cells and formation of reactive oxygen species.Am J Physiol Heart Circ Physiol,2006,290:H1777-87
[40]Hessler JR,Robertson AL Jr,Chisolm GM 3rd.LDLinduced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture.Atherosclerosis,1979,32:213-29
[41]Chen J,Mehta JL,Haider N,et al.Role of caspases in OxLDL-induced apoptotic cascade in human coronary artery endothelial cells.Circ Res,2004,94:370-76
[42]Sato Y,Fujiwara H,Takatsu Y.Biochemical markers in heart failure.J Cardiol,2012,59:1-7
[43]王馨佩,刘振华.线粒体在肺动脉高压发生中的研究进展.医学研究生学报,2017,30:204-7
[44]刘晓鹏.新型经导管置入主动脉瓣膜临床前研究及线粒体自噬对动脉粥样硬化保护机制研究[D].北京:北京协和医学院中国医学科学院清华大学医学部,2016
[45]朱晓彤,李广平.线粒体功能障碍与心力衰竭的关系.中国心血管杂志,2016,21:65-8
[46]Razani B,Feng C,Coleman T,et al.Autophagy links inflammasomes to atherosclerotic progression.Cell Metab,2012,15:534-44
[47]Akazawa H,Komazaki S,Shimomura H,et al.Diphtheria toxin-induced autophagic cardiomyocyte death plays a pathogenic role in mouse model of heart failure.J Biol Chem,2004,279:41095-103
[48]Yu T,Robotham JL,Yoon Y.Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology.Proc Natl Acad Sci USA,2006,103:2653-58
[49]Shenouda SM,Widlansky ME,Chen K,et al.Altered mitochondrial dynamics contributes to endothelial dysfunction in diabetes mellitus.Circulation,2011,124:444-53
[50]Makino A,Scott BT,Dillmann WH.Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1diabetes.Diabetologia,2010,53:1783-94
[51]Boengler K,Kosiol M,Mayr M,et al.Mitochondria and ageing:role in heart,skeletal muscle and adipose tissue.J Cachexia Sarcopenia Muscle,2017,8:349-69
[52]Michelakis ED,Thebaud B,Weir EK,et al.Hypoxic pulmonary vasoconstriction:redox regulation of O2-sensitive K+channels by a mitochondrial O2-sensor in resistance artery smooth muscle cells.J Mol Cell Cardiol,2004,37:1119-36
[53]Weir EK,Lopez-Barneo J,Buckler KJ,et al.Acute oxygen-sensing mechanisms.N Engl J Med,2005,353:2042-55
[54]Jones G,Zhang H,Colman M.The effect of bioenergetic impairment of cytosolic processes in spatio-temporal Ca2+dynamics in a three-dimensional cardiomyocyte model[C].2016 Computing in Cardiology Conference
[55]Semenza GL.Oxygen sensing,homeostasis,and disease.N Engl J Med,2011,365:537-47
[56]Chen X,Zhang Y,Xu B,et al.The mitochondrial calcium uniporter is involved in mitochondrial calcium cycle dysfunction:underlying mechanism of hypertension associated with mitochondrial t RNAIle A4263G mutation.Int J Biochem Cell Biol,2016,78:307-14
[57]林枝,姜丰,王恒,等.一个携带线粒体DNA t RNALeu(UUR)3253T>C突变的中国汉族原发性高血压家系临床及遗传特征分析[C].浙江省医学遗传学学术年会暨高通量基因测序产前筛查与诊断技术研讨会,2015
[58]Xu M,He Y,Geng J,et al.The mitochondrial t RNAMet/t RNAGlnA4401G and t RNACysG5821A mutations may be associated with hypertension in two Han Chinese families.Hereditas,2014,36:127-34
[59]Wang S,Li R,Fettermann A,et al.Maternally inherited essential hypertension is associated with the novel4263A>G mutation in the mitochondrial t RNAIle gene in a large Han Chinese family.Circ Res,2011,108:862-70
[60]肖云.高血压相关的线粒体新突变t RNAAla T5655C的致病机理研究[D].杭州:浙江大学,2013
[61]刘浩.母系遗传2型糖尿病相关的线粒体t RNA突变及其功能研究[D].浙江大学,2016
[62]Liu H,Li R,Li W,et al.Maternally inherited diabetes is associated with a homoplasmic T10003C mutation in the mitochondrial t RNAGly gene.Mitochondrion,2015,21:49-57
[63]Meng W,Peng Y,Jing Z,et al.A deafness-associated t RNAAsp mutation alters the m1G37 modification,aminoacylation and stability of t RNAAsp and mitochondrial function.Nucleic Acids Res,2016,44:10974
[64]Li G,Yong Y,Rui B.Mitochondrial DNA mutation m.5512A>G in the acceptor-stem of mitochondrial t RNATrp,causing maternally inherited essential hypertension.Biochem Biophys Res Commun,2016,479:800-7
[65]Gomes LC,Di Benedetto G,Scorrano L.During autophagy mitochondria elongate,are spared from degradation and sustain cell viability.Nat Cell Biol,2011,13:589-98
[66]Toyama EQ,Herzig S,Courchet J,et al.Metabolism.AMP-activated protein kinase mediates mitochondrial fission in response to energy stress.Science,2016,351:275-81
[67]Anand R,Langer T,Baker MJ.Proteolytic control of mitochondrial function and morphogenesis.Biochim Biophys Acta,2013,1833:195-204
[68]Givvimani S,Pushpakumar S,Veeranki S,et al.Dysregulation of Mfn2 and Drp-1 proteins in heart failure.Can J Physiol Pharmacol,2014,92:583-91
[69]Yu T,Robotham JL,Yoon Y.Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology.Proc Natl Acad Sci USA,2006,103:2653-8
[70]Trudeau K,Molina AJ,Guo W,et al.High glucose disrupts mitochondrial morphology in retinal endothelial cells:implications for diabetic retinopathy.Am J Pathol,2010,177:447-55
[71]Ambros V.The functions of animal micro RNAs.Nature2004,43l:350-5
[72]Guttman M,Donaghey J,Carey BW,et al.linc RNAs act in the circuitry controlling pluripotency and differentiation.Nature,2011,477:295-300
[73]Ishii N,Ozaki K,Mizuno H,et al.Identification of a novel non-coding RNA,MIAT,that confers risk of myocardial infarction.J Hum Genet,2006,51:1087-99
[74]Batlevi Y,Spada AR.Mitochondrial autophagy in neural function,neurodegenerative disease,neuron cell death,and aging.Neurobiol Dis,2011,43:46-51
[75]Kanki T,Klionsky DJ,Koji O.Mitochondria autophagy in yeast.Antioxiod Redox Signal,2011,14:1989-2001
[76]Youle RJ,Narendra DP.Mechanism of mitophagy.Nat Rev Mol Cell Biol,2011,12:9-14
[77]Cui C,Chen S,Qiao J,et al.PINK1-Parkin alleviates metabolic stress induced by obesity in adipose tissue and in 3T3-L1 preadipocytes.Biochem Biophys Commun,2018,498:445-52
[78]Heeman B,Van den Haute C,Aelvoet SA,et al.Pink1depletion affects mitochondrial homeostasis.Movement Disorders,2010,25:S624
[79]Tan AS,Baty JW,Dong LF,et al.Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA.Cell Metabolism,2015,21:81-94