细胞凋亡的线粒贴体途径.ppt

细胞凋亡的线粒体途径 蒋舜媛 董霞 程在全 2002-12-17 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 Programmed Cell Death Apoptosis 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. Fig.1. Schematic summary of biochemical mechanisms of apoptosis. 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。 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 inactivated (10). Such experimental observations argue that a caspase-independent mechanism for commitment to death exists. This mechanism is likely to involve mitochondria, as we will see. Mitochondrial Pathways in physiological cell death the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular ox