The extrinsic pathway is initiated by the binding of extracellular death ligands, such as Fas ligand or tumor necrosis factor (TNF), to their corresponding death receptors on the cell surface. This interaction activates the receptor and recruits adaptor proteins, forming the death-inducing signaling complex (DISC). This complex then activates initiator caspase-8, which either directly activates effector caspases or amplifies the apoptotic signal through the intrinsic pathway by cleaving Bid, a pro-apoptotic Bcl-2 family member.
