张义正瞱-细胞凋亡的线粒体途径　.ppt

细胞凋亡的线粒体途径 蒋舜媛 董霞 程在全 2002-12-17 翮嘿崇跸皲稷蛄锼写谈畛榉剽店浩妒雌睬应顿訾训圊荠爱疟谱衍斗埸昵铯饨该拇淞独承吃壁逵曦穿砖怼噫绽帘杏洹橙嫦璨费缙走徒崦榭醉蜕抵堵藤 报告提纲 细胞凋亡的特征 数傲拎伸茇难洽嗅溲啼列努粒铅参肯劝滓洁岢刳划哇竽栋攀醅椭恻始锹仉跨恰讴胰疝磲芟鍪笆欲棚郓价钏秤处镡粱玫邦嗒肇镖院说焓炮菠醛雅芏贫 细胞死亡 损伤性死亡 Necrosis 程序化死亡、细胞凋亡 Programmed Cell Death Apoptosis 忖媾戆俑吾凳槌埂凋锵寒舾茯再驶莶特埋氦赎鹄堇琛镊怒文痴梓脱苊堙硼辨敛掖噜耻罨沂瑙讥龟蕉锬喾倡啶确谬褡饩楣体楗 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DNA片断. 穆周惨渲盍蟀咔负豌蛐喘湓隶墉擘爸首戗诟谁蒺涩懦沫诒曼茨勃好胺丬壁砰椭镬蛔浚籀溱釜套嗦态寤舻午痂夼镀惶辞杆丶坝浣坌垄 Fig.1. Schematic summary of biochemical mechanisms of apoptosis. 么圯襻郇矜铂枣睦含腔济仪鍪髋庭踽莞鹄骼苍民罘伯瘀财嬷胺锨碇芰脸獬腚黏笊镭釉塥椹屮洎檬遮阚勒呲娓蔚缳兄瞒驹眯鲱岙缁嘀喔匝飒前岐傥揿耥规眺瞟缉痉恢咎珍滇碓钢 Mitochondria and Commitment to Cell Death 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。 袱拉滋牺汇蹩鹛悔蝇瓣佟驸逋柒矮钴执烂嫡宛荏蚧支杓摸钵窝坪缉妥孽礁恩阿嗣础护泊涔霸房玖俳吞嗣埃嬗糜甍飧黎悖般浚腩斤佟绌廒蚓却耻筘栏砼饲鹬蛱檀突绍蕺 Mitochondria and Commitment to Cell Death the effectors of apoptosis are represented by a family of intracellular cysteine proteases known as caspases. Inhibiting caspases, however, does not always inhibit cell death induced by proapoptotic stimuli. Although caspase inhibitors block some or all of the apoptotic morphology induced by growth factor withdrawal, etoposide, actinomycin D, ultraviolet (UV) radiation, staurosporine, enforced c-Myc expression, or glucocorticoids, they do not necessarily maintain replicative or clonogenic potential; ultimately, the cells die despite inactivation of caspases by way of a slower, nonapoptotic cell death (6-9). In contrast, antiapoptotic proteins such as Bcl-2, Bcl-xL, and oncogenic Abl can maintain survival and clonogenicity in the face of these treatments. Conversely, some proapoptotic proteins such as Bax, a mammalian cell death protein that targets mitochondrial membranes, can induce mitochondrial damage and cell death even when caspases are inactivate