Fig. 1

Schematic diagram of apoptotic signaling pathway. Apoptosis can be induced by the extrinsic or death receptor pathway and the intrinsic or mitochondrial pathway. The extrinsic pathway is initiated after an apoptotic ligand (e.g. FasL, TNF-α, TRAIL) binds to its death receptor. Subsequently, death-inducing signaling complex is formed resulting in caspase-8 activation. Caspase-8 activates effector caspases and triggers the terminal phase of the apoptotic cascade. The intrinsic pathway is initiated through wide range of none-receptor mediated stimuli (e.g. deprivation of growth factors, hypoxia, oxidative stress), resulting in changes of the mitochondrial membrane permeability. After its release from mitochondria, cytochrome c together with Apaf-1 and procaspases-9 forms an apoptosome, resulting in caspase-9 activation. Caspase-9 then activates effector caspases, such as caspase-3. AIF and EndoG are also released from mitochondria and translocate to cell nucleus where they cause DNA fragmentation, independently of caspase activation. Both extrinsic and intrinsic pathways converge on the same terminal pathway