Different pathways involved in apoptosis

Schematic representation of different pathways involved in apoptosis. Extrinsic pathway: 1. Ligand-death-receptor pathway (green): death factors such as Fas ligand (FasL) and tumour necrosis factor (TNF) trigger apoptosis by binding on 'death receptors' such as Fas and Tumour Necrosis Factor Receptor 1 (TNFR1). FasL may be solubilized to sFasL by matrix metalloproteinases (MMP's). The death receptors recruit procaspase-8 by means of an adaptor protein, Fas associated death domain protein (FADD). After cleavage the mature caspase-8 then directly activates caspase-3 or cleaves Bid. Truncated Bid (tBid) interacts with Bax and Bak. A pore is formed in the outer mitochondrial membrane through which cytochrome c (Cyt C) is released. 2. Cytolytic effector cell pathway (orange): cytotoxic T cells can release granzyme B and perforin, a pore-forming protein. Granzyme B activates caspase-3 through cleavage. It can also cleave caspase-8. 3. Growth factor depletion pathway (red): deprivation of survival factors triggers Cyt C release through activation of Bax and Bak. Intrinsic pathway: 4. Mitochondrial pathway (grey): mitochondria release cytochrome c (Cyt C) in response to stress. Together with apoptotic protease activating factor-1 (Apaf-1) and procaspase-9, Cyt C will form the apoptosome complex. This results in the proteolytic activation of the procaspase. Mature caspase-9 can then proteolytically activate caspase-3 and other executioner caspases. 5. Endoplasmatic reticulum pathway (blue): the ER can also induce apoptosis as a reaction to stress. It might do so by stimulating the mitochondrial pathway or by directly targeting the nucleus. In mice both caspase-7 and -12 are linked to this pathway. These different initiation pathways converge further downstream into activation of caspase-3. The effector caspase-3 cleaves ICAD (inhibitor of CAD) and releases it from CAD (caspase-activated DNAase). CAD translocates from the cytoplasm to the nucleus and can now act as active endonuclease and fragment DNA.

Publication

Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema. (2006) Ingel K Demedts, et al. Respir Res. 2006;7(1):53-53. Figure: F2. Homo sapiens

Disease mentions