The mitochondrial apoptotic pathway of p53. When p53 is targeted to the mitochondria, it interacts with anti-apoptotic Bcl-XL, enables Bax and Bak oligomerization, and activates the intrinsic apoptotic pathway. The apoptosome (cytochrome c, APAF-1 and caspase-9) is triggered, leading to apoptosis via activation of caspases-3, -6, and -7. The left side of the diagram indicates the mitochondrial signals (MTSs) used and the different subsections of the mitochondria targeted, including the outer membrane (“XL-MTS” from Bcl-XL; “TOM-MTS” from TOM20), the inner membrane (“CCO-MTS” from cytochrome c oxidase), and the matrix (“OTC-MTS” from ornithine transcarbamylase).