细胞器与疾病.ppt

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1、细胞器与疾病（分子医学）A mammalian cellNucleusThe nucleus is a membrane bound structure that contains the cells hereditary information and controls the cells growth and reproduction.It is commonly the most prominent organelle in the cellNuclear MembranesThe nuclear content is located in the nuclear lumennuclea

2、r lumen and is surrounded by a double membrane or nuclear envelopenuclear envelope,composed of inner membraneinner membrane and outerouter membranemembrane.The outer membrane is contiguous with the ERThe nuclear membrane contains nuclear nuclear porespores,which provide selective access into and out

3、 of the nuclear lumenThe inner membrane has a protein lining called the nuclear lamina,which binds to chromatin and other nuclear components.The Nuclear Pore Complexes form a form a continuous aqueous channel between cytoplasm&nucleoplasm-nuclear pore complex is large about 120 million Daltons-30 di

4、fferent proteins found in pore;basic subunit repeated 16 times.“Central granule now called transporter functions to move molecules through pore.There is a ring of proteins that anchors pore to N.E.and the basket of fibers with unknown function-no obvious motor proteins were found The NucleolusThe re

5、gion of the nucleus where portions of chromosomes that contain genes coding for ribosomal RNA are transcribed and ribosomal subunits are assembledStretch of DNA with rRNA genes nucleolar organizing region=(NOR)Ribosomal proteins are synthesized in cytoplasm and transported into the nucleusThese prot

6、eins self associate with appropriate rRNA during rRNA synthesis forming immature ribosomal subunitsRibosomes finish self assembly in cytoplasm Endoplasmic ReticulumKEDLR-GFP激光共聚焦显微镜下的ERThe Endoplasmin Reticulum(ER)is an extensive,extra-nuclear membrane system with the following functions:ER is a hom

7、e for various enzymes involved in protein folding,drug detoxification,membrane lipid biosynthesis,cholesterol and fatty acid metabolismER is an entry point for protein sorting.Targeting of these proteins is mediated by signal sequence.The membrane proteins are inserted into the ER membrane in their

8、proper orientation.Secreted proteins are translocated into ER lumen and then transported to the destination place Rough and Smooth ERTwo regions of the ER differ in both structure and function.Rough ER has ribosomes attached to the cytoplasmic side of the membrane.Smooth ER lacks attached ribosomes.

9、Typically,the smooth ER is a tubule network and the rough ER is a series of flattened sacs.http:/esg-www.mit.edu:8001/esgbio/cb/org/er.gifThe smooth ER has a wide range of functions including carbohydrate and lipid synthesis.It serves as a transitional area for vesicles that transport ER products to

10、 various destinations.In liver cells the smooth ER produces enzymes that help to detoxify certain compounds.In muscles the smooth ER assists in the contraction of muscle cells and in brain cells it synthesizes male and female hormones.The rough ER manufactures membranes and secretory proteins The ro

11、ugh and smooth ER areUsually interconnected and the proteinsand membranes made by the rough ER move into the smooth ER to be transferred to other locations.The cytoplasm has a reducing environment,while ER lumen is oxidizing.This difference is generated by unequal distribution of trypeptide glutathi

12、one and is essential for formation of disulfide bonds in proteins and for proper foldingER function-related diseases内质网应激与心血管疾病内质网与细胞凋亡内质网与PrP and Mad CowMitochondriaMitochondria(singular:mitochondrion)are the sites of aerobic respiration,and generally are the major energy production center in eukar

13、yotesThe number of mitochondria range from one to thousands per cells.They are often positioned in cells nearest to sites of energy utilizationOne of the richest sources of mitochondria is a hummingbird flight muscleMitochondria are a double membrane organelle in which the inner membrane is in-folde

14、d to form“cristae”.The outer membrane is a fairly simple phospholipid bilayer,containing porins,proteins that render it permeable to molecules of about 10 kilodaltons or less.Ions,nutrient molecules,ATP,ADP,etc.easily pass through the outer membrane and enter the intermembrane space The inner membra

15、ne is more complex and contains respiratory chains and transportersThe matrix lies within the inner membrane.The access to this compartment often requires specific transportersFour possible localization for mitochondrial enzymesThe Golgi ComplexLocated near cell nucleus,consists of flattened,membran

16、e-bounded sacs(cisternae)forming a stackEach stack has:cis-face is an entry face-adjacent to ER to accept incoming vesiclestrans-face is an exit face points towards plasma membrane,produces vesicles for forward flowThe function of the Golgi is to transport and process secreted and membrane proteins

17、from ER to the cell surfaceCis removal of mannose,phosphorylationMedial removal of mannose,addition of N-acetylglucosamineTrans Removal of galactose,addition of sialic acidTGN addition of sialic acid,SortingCisternae segregated into convex(cis),medial(middle),and concave(trans)compartments.ERcysmedi

18、altransTGNVesicular TransportGolgi structure/function/-related diseasesGolgi and MitosisGolgi and ApoptosisGolgi and Liver CancerHNE induces Golgi FragmentsControl30 min1 h2 h4 hThe Endocytic PathwayEndosomes and LysosomesLysosomes1、初级溶酶体、初级溶酶体 直径约直径约0.20.5um膜厚膜厚7.5nm，内含物均一，无，内含物均一，无明显颗粒，是高尔基体明显颗粒，是

19、高尔基体分泌形成的（如右图）。分泌形成的（如右图）。含有多种水解酶，但没含有多种水解酶，但没有活性，只有当溶酶体有活性，只有当溶酶体破裂，或其它物质进入，破裂，或其它物质进入，才有酶活性。其水解酶才有酶活性。其水解酶包括蛋白酶，核酸酶、包括蛋白酶，核酸酶、脂酶、磷酸酶、硫酸酯脂酶、磷酸酶、硫酸酯酶、磷脂酶类，已知酶、磷脂酶类，已知60余种，这些酶均属于酸余种，这些酶均属于酸性水解酶，反应的最适性水解酶，反应的最适PH值为值为5左右，溶酶体左右，溶酶体膜虽然与质膜厚度相近，膜虽然与质膜厚度相近，但成分不同但成分不同，2、次级溶酶体、次级溶酶体 这些都是消化泡，正这些都是消化泡，正在进行或完成消化

20、作在进行或完成消化作用的溶酶体，内含水用的溶酶体，内含水解酶和相应的底物，解酶和相应的底物，可分为自噬溶酶体可分为自噬溶酶体（autophagolysosome）和异噬溶酶体）和异噬溶酶体（phagolysosome），），前者消化的物质来自前者消化的物质来自细胞本身的各种组分细胞本身的各种组分,后者消化的物质来自后者消化的物质来自外源。外源。3、残体、残体 又称后溶酶体（又称后溶酶体（post-lysosome）已失去酶）已失去酶活性，仅留未消化的活性，仅留未消化的残渣故名，残体可通残渣故名，残体可通过外排作用排出细胞，过外排作用排出细胞，也可能留在细胞内逐也可能留在细胞内逐年增多，如肝细胞

21、中年增多，如肝细胞中的脂褐质（如右图）。的脂褐质（如右图）。LysosomesLysosomes are active in recycling the cells organic material and in the intracellular digestion of macromolecules.Lysosomes contain various hydrolytic enzymes that are capable of digesting nucleic acids,polysaccharides,fats and proteins.The inside of a lysosome

22、 is acidic.In humans,a variety of inherited conditions can affect lysosomes.These defects are called storage diseases.People with these disorders are missing one or more of the lysosomal hydrolytic enzymes.动物细胞溶酶体系统示意图 Lysosome-related diseases 溶酶体酶缺失或溶酶体酶的代谢环节故障，影响细胞代谢，引起疾病。如台-萨氏（Tay-Sachs）等各种储积症（隐

23、性的遗传病）。某些病原体（麻疯杆菌、利什曼原虫或病毒）被细胞摄入，进入吞噬泡但并未被杀死而繁殖（抑制吞噬泡的酸化或利用胞内体中的酸性环境）。类风湿性关节炎 溶酶体膜很易脆裂，其释放的酶导致关节组织损伤和发炎。矽肺 二氧化硅尘粒（矽尘）吸入肺泡后被巨噬细内吞噬，含有矽尘的吞噬小体与溶酶体合并成为次级溶酶体。二氧化硅的羟基与溶酶体膜的磷脂或蛋白形成氢键，导致吞噬细胞溶酶体崩解，细胞本身也被破坏，矽尘释出，后又被其他巨噬细内吞噬，如此反复进行。受损或已破坏的巨噬细胞释放“致纤维化因子”，并激活成纤维细胞，导致胶原纤维沉积，肺组织纤维化。The CytoskeletonCytoskeleton is

24、a network of protein filaments in the cytoplasmMain functions:Supports large volume of the cytoplasm.Participates in large-scale movements associated with the changes in cell shape and cell motility.Provides machinery for organelle transport,chromasome segregation during mitosis,and cell division.Ac

25、tin filamentsMicrotubulesIntermediate filamentsMajor components of cytoskeletonMajor components of cytoskeletonThe cytoskeletal filamentsCommon Features:Linear polymers of protein subunitsActin(8 nm in diameter)Intermediate Filaments(10 nm in diameter)Microtubules(24 nm in diameter)Filaments are dyn

26、amic,i.e.they can assemble and disassembleHighly conserved Intermediate FilamentsIntermediate filaments enable cells to withstand mechanical stress when cells are stretched.They can span the entire cytoplasm and are anchored to the plasma membrane.The Microtubule CytoskeletonAlso penetrates the enti

27、re volume of the cellWhereas actin fibers are concentrated at the periphery,most microtubules radiate from a central location in the cellMain functions:intracellular transport and mitosis Microtubules provide an organizational structure in an interphase cell and separate chromosomes in a dividing ce

28、llMicrotubulesMicrotubulesMicrotubules Provide Tracks for TransportMicrotubulesMicrotubules are long hollow cylinders made of tubulinProtofilaments are linear chains of tubulin dimers,a parallel bundle of 13 protofilaments forms a microtubuleThere are three kinds of tubulins,each with many subtypes:

29、a a-tubulin-tubulin and b b-tubulin-tubulin form a/b tubulin dimers and represent the basic building block of microtubulesg g-tubulin-tubulin is involved in more specialized processes,such as nucleationMicrotubules have a GTP“cap”stabilizing the ends.Motor ProteinsMotor proteins bind to microtubules

30、 and move by cycles of conformational changes using energy from ATP.One end of the protein can bind to specific cellular components.Actin is the most common protein in the cytoplasmActin filaments are concentrated beneath the plasma membrane and give the cell mechanical strengthAssembly of actin fil

31、aments can determine cell shape and cause cell movementAssociation of actin filaments with myosin can form contractile structuresActin filaments=microfilamentsActin filaments=microfilaments核蛋白体核蛋白体 在在粗粗面面内内质质网网表表面面的的称称固固着着核核蛋蛋白白体体，在在细细胞胞质质内内分分散散存存在在的的称称游游离离核核蛋蛋白白体体。数数个个或或致致十十个个核核蛋蛋白白体体聚聚集集在在一一起起称称多多

32、聚聚核核蛋蛋白白体体，系系由由信信息息核核糖糖核核酸酸(mRNA)(mRNA)将将核核蛋蛋白白体体串串连连在在一一起起形形成。成。核核蛋蛋白白体体在在一一定定浓浓度度的的镁镁离离子子溶溶液液内内，可可分分成成一一大大一一小小两两个个亚亚单单位位。分分别别称称为为大大亚亚基基与与小小亚亚基基，可可用用超超速速离离心心法法将将两两者者分分开开。两两个个亚亚基基合合在在一一起起时时，由由于于一一大大一一小小，形形成成葫葫芦芦状状。核核蛋蛋白白体体与与蛋蛋白白质质合合成成有有密密切切关关系系，是是氨氨基基酸酸根根据据mBNAmBNA中中的的遗遗传传密密码码顺顺序序形形成成多多肽肽的的场场所所。合合成成

33、内内用用蛋蛋白白质质多多的的细细胞胞，游游离离的的核核蛋蛋白白体体丰丰富富，如如幼幼稚稚细细胞胞或或胚胚胎胎细细胞胞。合合成成外外用用蛋蛋白白质质多多的的细细胞胞，则则粗粗面面内内质质网网丰丰富富，例例如如肝肝细细胞胞、胰胰腺腺泡泡细细胞胞及及浆浆细细胞等。胞等。中心粒中心粒(centrio1es)中中心心粒粒与与细细胞胞分分裂裂有有关关，在在间间期期，中中心心粒粒常常在在细细胞胞核核一一侧侧。中中心心粒粒呈呈短短简简状状，成成双双存存在在，彼彼此此垂垂直直分分布布，又又称称双双体体(diplosome)(diplosome)。每每个个中中心心粒粒由由9 9组组三三联联体体构构成成，彼彼此此成

34、成4545，使使9 9组组三三联联体体排排列列成成风风车车状状。每每个个三三联联体体由由3 3根根微微管管组组成成。在在核核分分裂裂时时，双双体体复复制制，并并移移向向细细胞胞的的两两极极。以以后后各各端端中中心心粒粒的的纺纺锤锤丝丝与与染染色色体体相相连连，并并将染色体引向两极，形成二个核。将染色体引向两极，形成二个核。线粒体遗传病线粒体遗传病18941894年，首次发现年，首次发现年，首次发现年，首次发现18971897年，正式命名为年，正式命名为年，正式命名为年，正式命名为mitochondrion(mitochondrion(线粒体线粒体线粒体线粒体)19631963年，年，年，年，N

35、assNass在鸡胚中发现线粒体中存在在鸡胚中发现线粒体中存在在鸡胚中发现线粒体中存在在鸡胚中发现线粒体中存在DNADNA SchatzSchatz分离到完整的线粒体分离到完整的线粒体分离到完整的线粒体分离到完整的线粒体DNADNA19811981年，测定人年，测定人年，测定人年，测定人mtDNAmtDNA的的的的DNADNA序列序列序列序列19871987年，年，年，年，WallacWallac提出提出提出提出mtDNAmtDNA突变可引起疾病突变可引起疾病突变可引起疾病突变可引起疾病19881988年，首次报道年，首次报道年，首次报道年，首次报道mtDNAmtDNA突变突变突变突变mtDN

36、A的结构和遗传特征的结构和遗传特征mtDNAmtDNA的结构特点的结构特点的结构特点的结构特点线线线线粒粒粒粒体体体体是是是是细细细细胞胞胞胞质质质质中中中中独独独独立立立立的的的的细细细细胞胞胞胞器器器器，也也也也是是是是动动动动物物物物细细细细胞胞胞胞核核核核外外外外唯唯唯唯一一一一的的的的含含含含有有有有DNA(mitochondrial DNA(mitochondrial DNADNA，mtDNA)mtDNA)的细胞器。的细胞器。的细胞器。的细胞器。19811981年年年年，剑剑剑剑桥桥桥桥大大大大学学学学的的的的AndersonAnderson小小小小组组组组测测测测定定定定了了了了

37、人人人人mtDNAmtDNA的完整的完整的完整的完整DNADNA序列，称为序列，称为序列，称为序列，称为“剑桥序列剑桥序列剑桥序列剑桥序列”。由由由由于于于于缺缺缺缺乏乏乏乏组组组组蛋蛋蛋蛋白白白白的的的的保保保保护护护护，线线线线粒粒粒粒体体体体亦亦亦亦缺缺缺缺乏乏乏乏DNADNA损损损损伤伤伤伤修复系统，修复系统，修复系统，修复系统，mtDNAmtDNA的突变率较高。的突变率较高。的突变率较高。的突变率较高。人人人人mtDNAmtDNA是是是是一一一一个个个个长长长长为为为为16,569 16,569 bpbp的的的的双双双双链链链链闭闭闭闭合合合合环环环环状状状状分分分分子子子子，外外外

38、外环环环环含含含含GG较较较较多多多多，称称称称重重重重链链链链(H(H链链链链)，内内内内环环环环含含含含C C较较较较多，称轻链多，称轻链多，称轻链多，称轻链(L(L链链链链)。mtDNA的结构和遗传特征的结构和遗传特征mtDNAmtDNA结结结结构构构构紧紧紧紧凑凑凑凑，没没没没有有有有内内内内含含含含子子子子，唯唯唯唯一一一一的的的的非非非非编编编编码码码码区区区区是是是是D D环环环环区区区区，长长长长约约约约1,000 1,000 bpbp左右。左右。左右。左右。D D环环环环 区区区区 包包包包 括括括括 mtDNAmtDNA重重重重链链链链复复复复制制制制起起起起始始始始点点点

39、点，重重重重轻轻轻轻链链链链转录的启动子。转录的启动子。转录的启动子。转录的启动子。线线线线粒粒粒粒体体体体的的的的HH链链链链是是是是1212种种种种多多多多肽肽肽肽链链链链、12S 12S rRNArRNA、16S 16S rRNArRNA和和和和1414种种种种tRNAtRNA的的的的转转转转录录录录模模模模板板板板，L L链链链链是是是是1 1种种种种多多多多肽肽肽肽链链链链和和和和8 8种种种种tRNAtRNA转录的模板。转录的模板。转录的模板。转录的模板。人人人人类类类类的的的的mtDNAmtDNA编编编编码码码码1313条条条条多多多多肽肽肽肽链链链链、2222种种种种tRNAt

40、RNA和和和和2 2种种种种rRNArRNA。1313种种种种蛋蛋蛋蛋白白白白质质质质均均均均是是是是呼呼呼呼吸吸吸吸链链链链酶酶酶酶复复复复合合合合物物物物的的的的亚亚亚亚单位。单位。单位。单位。由由由由于于于于缺缺缺缺乏乏乏乏组组组组蛋蛋蛋蛋白白白白的的的的保保保保护护护护，线线线线粒粒粒粒体体体体亦亦亦亦缺缺缺缺乏乏乏乏DNADNA损损损损伤伤伤伤修复系统，修复系统，修复系统，修复系统，mtDNAmtDNA的突变率较高。的突变率较高。的突变率较高。的突变率较高。一、一、一、一、mtDNAmtDNA的结构特征的结构特征的结构特征的结构特征线线线线粒粒粒粒体体体体是是是是细细细细胞胞胞胞质质

41、质质中中中中独独独独立立立立的的的的细细细细胞胞胞胞器器器器，也也也也是是是是动动动动物物物物细细细细胞胞胞胞核外唯一的含有核外唯一的含有核外唯一的含有核外唯一的含有DNADNA的细胞器。的细胞器。的细胞器。的细胞器。19811981年年年年，剑剑剑剑桥桥桥桥大大大大学学学学的的的的AndersonAnderson小小小小组组组组测测测测定定定定了了了了人人人人mtDNAmtDNA的完整的完整的完整的完整DNADNA序列，称为序列，称为序列，称为序列，称为“剑桥序列剑桥序列剑桥序列剑桥序列”。第一节第一节 mtDNA的结构和遗传特征的结构和遗传特征1.mtDNA1.mtDNA具有半自主性具有半

42、自主性具有半自主性具有半自主性mtDNAmtDNA的遗传学特性的遗传学特性的遗传学特性的遗传学特性ComplexSubunitsNuclearmtDNA41347440111011310314122837013mtDNAmtDNA的的的的UGAUGA编编编编码码码码色色色色氨氨氨氨酸酸酸酸，而而而而非非非非终终终终止止止止信信信信号号号号。其其其其tRNAtRNA的通用性较强，的通用性较强，的通用性较强，的通用性较强，2222个个个个tRNAtRNA可识别可识别可识别可识别4848个密码子。个密码子。个密码子。个密码子。3.mtDNA3.mtDNA为母系遗传为母系遗传为母系遗传为母系遗传2.m

43、tDNA2.mtDNA的遗传密码与通用密码不同的遗传密码与通用密码不同的遗传密码与通用密码不同的遗传密码与通用密码不同1.mtDNA1.mtDNA具有半自主性具有半自主性具有半自主性具有半自主性mtDNAmtDNA的遗传学特征的遗传学特征的遗传学特征的遗传学特征mtDNA的母系遗传的母系遗传 1、母亲将她的、母亲将她的mtDNA传递给儿子和女儿，但只有女儿能传递给儿子和女儿，但只有女儿能 将其将其 mtDNA传递给下一代；传递给下一代；2、人的细胞里通常有上千个、人的细胞里通常有上千个mtDNA拷贝，在突变体和正拷贝，在突变体和正 常常mtDNA共存的细胞中，子细胞出现三种基因型：纯共存的细胞

44、中，子细胞出现三种基因型：纯 合的突变体、纯合的正常、突变体和正常的的杂合合的突变体、纯合的正常、突变体和正常的的杂合;3、线粒体病发病有一阈值，只有当异常的、线粒体病发病有一阈值，只有当异常的mtDNA超过阈超过阈 值才发病。女性携带者未发病，但仍可以通过值才发病。女性携带者未发病，但仍可以通过mtDNA 突变体向下代传递。突变体向下代传递。母系遗传的特点：母系遗传的特点：mtDNAmtDNA的遗传学特征的遗传学特征的遗传学特征的遗传学特征1.mtDNA1.mtDNA具有半自主性具有半自主性具有半自主性具有半自主性2.mtDNA2.mtDNA的遗传密码与通用密码不同的遗传密码与通用密码不同的

45、遗传密码与通用密码不同的遗传密码与通用密码不同3.mtDNA3.mtDNA为母系遗传为母系遗传为母系遗传为母系遗传4.mtDNA4.mtDNA在有丝分裂和减数分裂间都要经过在有丝分裂和减数分裂间都要经过在有丝分裂和减数分裂间都要经过在有丝分裂和减数分裂间都要经过复制分离复制分离复制分离复制分离5.mtDNA5.mtDNA的杂质性与阈值效应的杂质性与阈值效应的杂质性与阈值效应的杂质性与阈值效应6.mtDNA6.mtDNA的突变率和进化率极高的突变率和进化率极高的突变率和进化率极高的突变率和进化率极高线粒体基因突变与线粒体基因病线粒体基因突变与线粒体基因病对对对对mtDNAmtDNA分分分分子子子

46、子病病病病理理理理学学学学的的的的研研研研究究究究证证证证实实实实mtDNAmtDNA突突突突变变变变在在在在许许许许多多多多疾疾疾疾病病病病中中中中存存存存在在在在，包包包包括括括括具具具具有有有有母母母母系系系系遗遗遗遗传传传传特特特特征征征征的的的的疾疾疾疾病病病病，中中中中老年时发病的一些退化性疾病，甚至衰老本身。老年时发病的一些退化性疾病，甚至衰老本身。老年时发病的一些退化性疾病，甚至衰老本身。老年时发病的一些退化性疾病，甚至衰老本身。线粒体突变导致的疾病主要累及肌肉、中枢和外线粒体突变导致的疾病主要累及肌肉、中枢和外周神经系统，与贫血和糖尿病等疾病也相关。周神经系统，与贫血和糖尿病

47、等疾病也相关。线粒体遗传病（线粒体遗传病（mitochondrial diseases）致病基因位于线粒体基因组上，由于受精卵的致病基因位于线粒体基因组上，由于受精卵的 细胞质主要来自卵子，存在于细胞质中的线粒体也细胞质主要来自卵子，存在于细胞质中的线粒体也 来自卵子，所以线粒体遗传病表现为母系遗传，即来自卵子，所以线粒体遗传病表现为母系遗传，即 男女均可患病，但只有女性患者的子代患病，男性男女均可患病，但只有女性患者的子代患病，男性 患者子代正常。患者子代正常。线粒体线粒体线粒体线粒体DNADNA的突变类型的突变类型的突变类型的突变类型(一一一一)碱基突变碱基突变碱基突变碱基突变也也也也称称

48、称称氨氨氨氨基基基基酸酸酸酸替替替替换换换换突突突突变变变变，主主主主要要要要与与与与脑脑脑脑脊脊脊脊髓髓髓髓性性性性及及及及神神神神经经经经性性性性疾疾疾疾病病病病有有有有关关关关，常常常常见见见见有有有有LeberLeber遗遗遗遗传传传传性性性性视视视视神神神神经经经经病病病病(LHON)(LHON)(MIM 535000)(MIM 535000)和神经肌病。和神经肌病。和神经肌病。和神经肌病。1.1.错义突变错义突变错义突变错义突变比比比比错错错错义义义义突突突突变变变变的的的的疾疾疾疾病病病病表表表表型型型型更更更更具具具具有有有有系系系系统统统统性性性性特特特特征征征征，且且且且所

49、所所所有有有有生生生生物物物物合合合合成成成成基基基基因因因因突突突突变变变变都都都都为为为为tRNAtRNA突突突突变变变变，并并并并与与与与线线线线粒粒粒粒体体体体肌肌肌肌病病病病相相相相关关关关。主主主主要要要要有有有有MERRFMERRF综综综综合合合合征征征征(癫癫癫癫痫痫痫痫伴伴伴伴碎碎碎碎红红红红纤纤纤纤维维维维病病病病)(MIM 545000)(MIM 545000)。2.2.蛋白质生物合成基因突变蛋白质生物合成基因突变蛋白质生物合成基因突变蛋白质生物合成基因突变线粒体线粒体线粒体线粒体DNADNA的突变类型的突变类型的突变类型的突变类型(一一一一)碱基突变碱基突变碱基突变碱基

50、突变1.1.错义突变错义突变错义突变错义突变mtDNAmtDNA缺缺缺缺失失失失突突突突变变变变引引引引起起起起绝绝绝绝大大大大多多多多数数数数眼眼眼眼肌肌肌肌病病病病，这这这这种种种种缺缺缺缺失导致的疾病一般无家族史。失导致的疾病一般无家族史。失导致的疾病一般无家族史。失导致的疾病一般无家族史。线粒体线粒体线粒体线粒体DNADNA的突变类型的突变类型的突变类型的突变类型2.2.蛋白质生物合成基因突变蛋白质生物合成基因突变蛋白质生物合成基因突变蛋白质生物合成基因突变(一一一一)碱基突变碱基突变碱基突变碱基突变1.1.错义突变错义突变错义突变错义突变(二二二二)缺失、插入突变缺失、插入突变缺失、