Apoptosis. Apoptosis can be initiated by the extrinsic or intrinsic pathways. The extrinsic pathway involves binding of ligands, such as tumor necrosis factor (TNF) or Fas ligand (FasL) to the death receptor. Subsequently, FAS-associating death domain (FADD) adapter protein is recruited to the receptor which leads to activation of caspase-8. The intrinsic pathway is initiated by cellular stress which induces loss of mitochondrial membrane potential, release of cytochrome C, and activation of caspase-9. The mitochondrial apoptotic pathway is controlled by the proapoptotic and antiapoptotic members of the Bcl-2 family. Cytochrome C release is inhibited by the prosurvival members Bcl-2/Bcl-xL and promoted by proapoptotic BAX/BIM. Both extrinsic and intrinsic pathways lead to activation of caspase-3 and, ultimately, cell death by apoptosis [40].