Cell death decision by p53 via control of the mitochondrial membrane

The tumor suppressor p53 is mutated in more than half of human cancers. Recent evidence has revealed that p53 not only regulates apoptosis but also regulates necrotic/necroptotic cell death via the mitochondria. The regulation of apoptosis by p53 is tightly connected to the mitochondrial outer membrane permeabilization and the induction of and interaction with Bcl-2 family members. Interestingly, p53-mediated regulation of necrosis/necroptosis is correlated with mitochondrial permeabilization pore opening via interactions with CypD and Drp1. This review discusses the p53-regulating molecules that induce apoptosis or necrosis/necroptosis via the mitochondria.