The intrinsic pathway is tightly regulated by pro-apoptotic and anti-apoptotic members of the Bcl-2 family. Anti-apoptotic proteins such as Bcl-2 and Bcl-xL work to inhibit the activation of Bax and Bak, thus preventing the release of cytochrome c. Conversely, pro-apoptotic proteins like Bax, Bak, and BH3-only proteins promote apoptosis by facilitating mitochondrial outer membrane permeabilization.