The Mitochondrial Pathways of Apoptosis
The Mitochondrial Pathways of Apoptosis
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DOI：
10.1007/978-94-007-2869-1_7
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发表时间：
2012-01-01
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影响因子：
--
通讯作者：
Mignotte, Bernard
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文献类型：
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作者：
Estaquier, Jerome;Vallette, Francois;Mignotte, Bernard
细胞凋亡是一种程序性细胞死亡过程，是精确调节细胞数量的主要机制，也是去除不需要的和潜在危险细胞的防御机制。对线虫、果蝇和哺乳动物的研究表明，尽管细胞死亡机制的调节在某种程度上因物种而异，但它是由同源蛋白质控制的，并涉及线粒体。在哺乳动物中，半胱天冬酶（作为细胞凋亡的主要执行者的半胱氨酸蛋白酶）的激活受到Bcl-2家族蛋白的严格控制，Bcl-2家族蛋白是根据第一个发现的哺乳动物细胞死亡调节剂命名的。这些蛋白质主要通过调节半胱天冬酶激活剂从线粒体的释放而起作用。虽然很长一段时间以来，线粒体的变化被认为是细胞凋亡的标志，线粒体今天似乎作为细胞凋亡的中央刽子手。在这一章中，我们提出了目前对线粒体凋亡途径的看法，特别关注Bcl-2蛋白家族控制线粒体膜透化的调节的新方面：在细胞凋亡过程中涉及其线粒体靶向和激活的机制，抑癌蛋白p53在线粒体中的功能以及线粒体融合和分裂过程中的作用
Apoptosis is a process of programmed cell death that serves as a major mechanism for the precise regulation of cell numbers, and as a defense mechanism to remove unwanted and potentially dangerous cells. Studies in nematode, Drosophila and mammals have shown that, although regulation of the cell death machinery is somehow different from one species to another, it is controlled by homologous proteins and involves mitochondria. In mammals, activation of caspases (cysteine proteases that are the main executioners of apoptosis) is under the tight control of the Bcl-2 family proteins, named in reference to the first discovered mammalian cell death regulator. These proteins mainly act by regulating the release of caspases activators from mitochondria. Although for a long time the absence of mitochondrial changes was considered as a hallmark of apoptosis, mitochondria appear today as the central executioner of apoptosis. In this chapter, we present the current view on the mitochondrial pathway of apoptosis with a particular attention to new aspects of the regulation of the Bcl-2 proteins family control of mitochondrial membrane permeabilization: the mechanisms implicated in their mitochondrial targeting and activation during apoptosis, the function(s) of the oncosuppressive protein p53 at the mitochondria and the role of the processes of mitochondrial fusion and fission