Shakeri Raheleh, Kheirollahi Asma, Davoodi Jamshid
Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran.
Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Science, Tehran, Iran.
Biochimie. 2017 Apr;135:111-125. doi: 10.1016/j.biochi.2017.02.001. Epub 2017 Feb 9.
Apoptosis, a form of programmed cell death, is responsible for eliminating damaged or unnecessary cells in multicellular organisms. Various types of intracellular stress trigger apoptosis by induction of cytochrome c release from mitochondria into the cytosol. Apoptotic protease activating factor-1 (Apaf-1) is a key molecule in the intrinsic or mitochondrial pathway of apoptosis, which oligomerizes in response to cytochrome c release and forms a large complex known as apoptosome. Procaspase-9, an initiator caspase in the mitochondrial pathway, is recruited and activated by the apoptosome leading to downstream caspase-3 processing. Various cellular proteins and small molecules can modulate apoptosome formation and function directly or indirectly. Despite recent progress in understanding the mitochondrial pathway of apoptosis, numerous questions such as the molecular mechanism of Apaf-1 oligomerization and caspase-9 activation remain poorly understood. In addition, reports have emerged showing non-apoptotic functions for Apaf-1. The current review summarizes the latest findings regarding structure-function relationship of Apaf-1 as well as its modifiers.
细胞凋亡是一种程序性细胞死亡形式，负责清除多细胞生物中受损或不必要的细胞。各种类型的细胞内应激通过诱导细胞色素c从线粒体释放到细胞质中触发细胞凋亡。凋亡蛋白酶激活因子-1（Apaf-1）是细胞凋亡内在或线粒体途径中的关键分子，它响应细胞色素c的释放而寡聚化，形成一种称为凋亡小体的大复合物。Procaspase-9是线粒体途径中的起始半胱天冬酶，被凋亡小体招募并激活，导致下游半胱天冬酶-3的加工。各种细胞蛋白和小分子可以直接或间接调节凋亡小体的形成和功能。尽管最近在理解细胞凋亡的线粒体途径方面取得了进展，但许多问题，如Apaf-1寡聚化和半胱天冬酶-9激活的分子机制，仍然知之甚少。此外，有报道显示Apaf-1具有非凋亡功能。本综述总结了关于Apaf-1及其调节剂的结构-功能关系的最新发现。
