Cells also activate their apoptosis program from inside the cell, usually in response to injury or other stresses, such as DNA damage, lack of oxygen, nutrients, extracellular survival signals.

• [ ] 细胞色素c的发现与鉴定

  Mechanism of caspase activation : 1996年，Emory大学, 王晓东博士研究小组, a cell-free system, theoretically possible to study caspase activation。

  在HeLa细胞提取物中加入dATP能够诱发caspase-3降解，以及外源细胞核DNA断裂等典型的凋亡特征。HeLa细胞提取物经过柱层析后分为两种组分，流出组分和吸附组分，并发现这两种组分只有合并起来才能诱导凋亡。

  • 吸附组分: 15kD的蛋白是凋亡的必需因子, 细胞色素 c， a puzzling finding since it is the essential protein in energy production.
  • 流出组分:
    • Apaf-1: the downstream binding partner of cytochrome c , the homolog of C. elegans Ced-4.
    • Caspase-9: homolog of C. elegans Ced-3.

  The discovery of cytochrome c-mediated caspase activation pathway delineated a mammalian activation pathway that is the counterpart of the C. elegans cell death pathway.

• Two models of ways in which ced-9 might act as a negative regulator of ced-3 and ced-4 function