Portrait of a Killer: The Mitochondrial Apoptosome Emerges From the Shadows

Caspase activation pathways. Initiator caspases are activated through protein–protein interactions, whereas effector caspases are activated through cleavage by initiator caspases. Two major pathways to caspase activation are illustrated. Binding of Fas ligand (FasL) to Fas induces oligomerization of caspase-8 through the adapter molecule FADD. Activated caspase-8 processes and activates caspase-3, leading to further caspase activation events and substrate proteolysis. In certain cells, caspase-8 also activates the mitochodrial pathway by cleaving the Bcl-2 family member Bid, leading to the release of cytochrome c from the intermembrane space and formation of the apoptosome. FADD, Fas-associated death domain–containing molecule. Bid, Bcl-2 homology 3–interacting domain death agonist. Apoptosome reprinted from Acehan et al. Molecular Cell 9, 423–432 (2002), with permission from Elsevier.