Figure 1

Intrinsic apoptosis signaling pathway. (A) Schematic diagram of the intrinsic or mitochondria apoptosis signaling pathway. Upon the release of Cytochrome C from mitochondria, it binds with apoptotic protease activating factor 1 (Apaf-1) to form the apoptosome. The apoptosome activates procaspase-9 into caspase 9, the initiator apoptotic caspase. Caspase 9 then cleaves and activates procaspase-3 to caspase3, the executioner or effector caspase. In turn, caspase 3 promotes the activation of caspase 9, forming a positive feedback loop. Meanwhile, the inhibitor of apoptosis protein (IAP) inhibits the activity of caspase 3. Elevated activity of caspase 3 induces irreversible fate of apoptosis. (B) Reaction scheme of our mathematical model of intrinsic apoptosis pathway, where Apaf-1, Cytochrome C, apoptosome, procaspase-9, caspase 9, procaspase-3 and caspase 3 are denoted by Apaf1, CC, a1cc, c9p, c9a, c3p and c3a, respectively. Note that the black arrows represent direct reactions such as binding, synthesis and degradation, the red line with hammerhead represents inhibiting regulatory reaction, and the two green arrows represent activating regulations, which are the modifications of the Fussenegger model.