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1、细胞凋亡的线粒体途径蒋舜媛董霞程在全2002-12-17报告提纲细胞凋亡的特征细胞死亡损伤性死亡Necrosis程序化死亡、细胞凋亡ProgrammedCellDeathApoptosis细胞凋亡的特征形态学特征:染色质的凝集,嗜碱性染色增强,细胞核崩解此时线粒体保持形态正常.细胞体积缩小,一部分细胞质和核碎片进入由膜包被的程序死亡小体,他们从细胞表面出芽脱落,并被巨噬细胞.上皮细胞吞噬.生化特征:染色质降解,核小体间连接DNA部位被降解,产生寡聚核小体DNA片段,即180-200DP整数倍的不同长度的
2、DNA片断.Fig.1.Schematicsummaryofbiochemicalmechanismsofapoptosis.MitochondriaandCommitmenttoCellDeath线粒体是真核细胞的重要细胞器，是动物细胞生成ATP的主要地点。线粒体基质的三羧酸循环酶系通过底物脱氢氧化生成NADH。NADH通过线粒体内膜呼吸链氧化。与此同时，导致跨膜质子移位形成跨膜质子梯度和/或跨膜电位。线粒体内膜上的ATP合成酶利用跨膜质子梯度能量合成ATP。合成的ATP通过线粒体内膜ADP/ATP载
3、体与细胞质中ADP交换进入细胞质，参与细胞的各种需能过程。MitochondriaandCommitmenttoCellDeaththeeffectorsofapoptosisarerepresentedbyafamilyofintracellularcysteineproteasesknownascaspases.Inhibitingcaspases,however,doesnotalwaysinhibitcelldeathinducedbyproapoptoticstimuli.Althoughca
4、spaseinhibitorsblocksomeoralloftheapoptoticmorphologyinducedbygrowthfactorwithdrawal,etoposide,actinomycinD,ultraviolet(UV)radiation,staurosporine,enforcedc-Mycexpression,orglucocorticoids,theydonotnecessarilymaintainreplicativeorclonogenicpotential;ulti
5、mately,thecellsdiedespiteinactivationofcaspasesbywayofaslower,nonapoptoticcelldeath(6-9).Incontrast,antiapoptoticproteinssuchasBcl-2,Bcl-xL,andoncogenicAblcanmaintainsurvivalandclonogenicityinthefaceofthesetreatments.Conversely,someproapoptoticproteinssu
6、chasBax,amammaliancelldeathproteinthattargetsmitochondrialmembranes,caninducemitochondrialdamageandcelldeathevenwhencaspasesareinactivated(10).Suchexperimentalobservationsarguethatacaspase-independentmechanismforcommitmenttodeathexists.Thismechanismislik
7、elytoinvolvemitochondria,aswewillsee.MitochondrialPathwaysinphysiologicalcelldeaththereleaseofcaspaseactivators(suchascytochromec),changesinelectrontransport,lossofmitochondrialtransmembranepotential,alteredcellularoxidation-reduction,participationofpro-
8、andantiapoptoticBcl-2familyproteins.MitochondrialPathwaysinphysiologicalcelldeathIfmitochondriaarepivotalincontrollingcelllifeanddeath,thenhowdotheseorganelleskill?Atleastthreegeneralmechanismsareknown,andtheireffectsmaybe
