Cereghetti G M, Scorrano L
Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova, Italy.
Oncogene. 2006 Aug 7;25(34):4717-24. doi: 10.1038/sj.onc.1209605.
Mitochondria integrate apoptotic signalling by releasing cytochrome c and other proapoptotic cofactors needed for activation of effector caspases. Previously overlooked morphological changes, mitochondrial fragmentation and cristae remodelling, emerged as subroutines of the mitochondrial programme of apoptosis in mammalian cells, as well as in developmental cell death of Caenorhabditis elegans. Mitochondrial morphology results from fusion and fission processes, controlled by a growing set of 'mitochondria-shaping' proteins. Their levels and function appear to influence mitochondrial pathways of cell death, but mechanisms are largely unknown. An emerging model implicates different signals converging on mitochondria-shaping proteins to activate or deactivate them during apoptosis. In turn, these proteins can orchestrate changes in mitochondrial shape to insure cytochrome c release and progression of the apoptotic cascade. These therefore appear an appealing novel therapeutic target to modulate cell death in cancer.
线粒体通过释放细胞色素c和其他激活效应半胱天冬酶所需的促凋亡辅因子来整合凋亡信号。以前被忽视的形态学变化，即线粒体碎片化和嵴重塑，已成为哺乳动物细胞以及秀丽隐杆线虫发育性细胞死亡中线粒体凋亡程序的子程序。线粒体形态由融合和裂变过程决定，这些过程由越来越多的“线粒体塑形”蛋白控制。它们的水平和功能似乎会影响细胞死亡的线粒体途径，但机制在很大程度上尚不清楚。一个新兴的模型表明，不同的信号汇聚在线粒体塑形蛋白上，在凋亡过程中激活或失活它们。反过来，这些蛋白可以协调线粒体形状的变化，以确保细胞色素c的释放和凋亡级联反应的进行。因此，这些蛋白似乎是调节癌症细胞死亡的一个有吸引力的新治疗靶点。
