Intrinsic and extrinsic apoptotic pathways

Intrinsic and extrinsic apoptotic pathways. The extrinsic pathway is initiated by binding of ligands (FasL, tumour necrosis factor, or other cytokines) to death receptors, which recruits the adaptor protein Fas-associated Death Domain (FADD), and, consequently, procaspase-8. The formation of the death-inducing-signaling-complex (DISC) results in cleavage and auto-activation of caspase-8. The activated caspase-8 can then proteolytically activate downstream caspases (particularly caspase-3), which induce cell shrinkage, membrane blebbing and DNA fragmentation. Apoptosis can also be triggered by various apoptotic stimuli, which results in the activation of the intrinsic pathway. Here, caspase-8 cleaves and activates Bid. Subsequently, t-Bid translocates to the mitochondria where it can induce the oligomerization of Bax and/or Bak in the outer mitochondrial membrane leading to cytochrome c release. Afterwards, Apaf-1 binds cytochrome c and recruits caspase-9 to form a large complex, called apoptosome, which is responsible for the following avtivation of caspase-3. Anti-apoptotic Bcl-2 and Bcl-xL oppose the effecst of Bid and Bax.

Publication

Glycosidated phospholipids: uncoupling of signalling pathways at the plasma membrane. (2010) Kerstin Danker, et al. Br J Pharmacol. 2010 May;160(1):36-47. Figure: F3. All organisms Drosophila melanogaster Homo sapiens

Disease mentions