Shi Y
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA.
Nat Struct Biol. 2001 May;8(5):394-401. doi: 10.1038/87548.
Mitochondria-mediated apoptosis plays a central role in animal development and tissue homeostasis, and its alteration results in a range of malignant disorders including cancer. Upon apoptotic stimuli, the mitochondrial proteins cytochrome c and Smac/DIABLO are released into the cytosol, where they synergistically activate caspases by activating Apaf-1 and relieving the apoptotic inhibition by IAPs. Recent biochemical and structural studies reveal a molecular basis for these important events and identify an evolutionarily conserved mechanism of apoptosis from fruit flies to mammals.
线粒体介导的细胞凋亡在动物发育和组织稳态中起核心作用，其改变会导致包括癌症在内的一系列恶性疾病。在凋亡刺激下，线粒体蛋白细胞色素c和Smac/DIABLO释放到细胞质中，在那里它们通过激活凋亡蛋白酶激活因子-1（Apaf-1）并解除凋亡抑制蛋白（IAPs）对凋亡的抑制作用，从而协同激活半胱天冬酶。最近的生化和结构研究揭示了这些重要事件的分子基础，并确定了从果蝇到哺乳动物的一种进化上保守的细胞凋亡机制。
