Fig. 1.

TRAIL apoptosis signaling. On binding of TRAIL to death receptors DR4 or DR5, the apoptosis signal can be transmitted in two ways, depending on the particular cell type. In type I cells, caspase-8 activation can directly activate downstream effector caspases such as caspase-3, and there is no requirement for any participation of the mitochondria. In type II cells, caspase-8 activation needs to cleave Bid, resulting in mitochondrial perturbation, release of cytochrome c and Smac/DIABLO, and additional activation of the intrinsic apoptosis signaling pathway. In type II cells, this mitochondrial amplification loop is required for apoptosis to occur (figure adapted from Holoch and Griffith, European Journal of Pharmacology [49])