Apoptosis pathway

The apoptosis pathway. Apoptosis is activated by intrinsic and extrinsic pathways. In the intrinsic pathway, certain apoptotic stimuli alter the normal status of the Bcl-2 family of proteins (), which leads to permeabilization of the mitochondrial membrane. Under normal circumstances, the pro-survival proteins of the Bcl-2 family protect the mitochondrial membrane. Once cytochrome c (CytoC) is released into the cytosol, it binds to the apoptosome [], a complex of proteins made up of the apoptosis activating factor-1 (Apaf1) protein and the initiator caspase-9. A morphological change in the apoptosome results from cytochrome c binding, which causes caspase-9 to become activated. Caspase-9 activates the effector caspase-3, leading to apoptosis []. Caspase-3 is known as the ‘executioner caspase’, because it activates or cleaves various protein targets, which is detrimental to the cell and results in death []. Activation of caspase-9 and caspase-3 are normally inhibited by a family of proteins known as the inhibitor of apoptosis proteins (IAPs), and XIAP (X-linked IAP) is the most potent IAP []. In the extrinsic pathway, ligands such as Fas ligand (FasL) or tumor necrosis factor α (TNF-α) bind to death receptors on the membrane of the host cell. Trimerization of the death receptors follows, forming what is known as the death-inducing signaling complex (DISC), which includes the Fas-associated death domain (FADD) adaptor protein, the Flice-like inhibitory protein (FLIP), and procaspase-8 []. Caspase-8 is activated, which in turn directly activates caspase-3 []. In addition, caspase-8 activates the pro-apoptotic protein Bid, which stimulates the intrinsic pathway to enhance the apoptotic signal, because Bid activation eventually leads to cytochrome c release [].

Publication

Staying alive: bacterial inhibition of apoptosis during infection. () Christina S. Faherty, et al. Trends Microbiol. ;16(4):173-180. Figure: F1. All organisms Homo sapiens Rattus norvegicus Danio rerio

Disease mentions