So far three caspase-related signaling pathways have been identified that can lead to apoptosis [103,125,126,157], but crosstalk among these pathways is possible. The intrinsic mitochondria-mediated pathway is controlled by Bcl-2 family proteins. It is regulated by cytochrome c release from mitochondria, promoting the activation of caspase-9 through Apaf1 and then caspase-3 activation. The extrinsic death receptor pathway involves the activation of cell-surface death receptors (see below), including Fas and tumor necrosis factor receptor, leading to the formation of the death-inducing signaling complex (DISC) and caspase-8 activation that in turn cleaves and activates downstream caspases such as caspase-3, -6, and -7. Caspase-8 can also cleave Bid leading to the translocation, oligomerization, and insertion of Bax or Bak1 into the mitochondrial membrane. Another pathway involves the activation of caspase-2 by DNA damage or ER stress as a pre-mitochondrial signal [158].