p53 mediates autophagy and cell death by a mechanism contingent upon Bnip3
Autophagy is a process by which cells re-cycle organelles and macromolecular proteins during cellular stress. Defects in the regulation of autophagy have been associated with various human pathologies including heart failure. In the heart tumor suppressor p53 protein is known to promote apoptotic and autophagic cell death. We found p53 over-expression increased endogenous protein level of the hypoxia-inducible Bcl-2 death gene Bnip3 which leads to loss of mitochondrial membrane potential (ΔΨm). This was accompanied by autophagic flux and cell death. Conversely, loss of function of Bnip3 in cardiac myocytes or Bnip3-/- mouse embryonic fibroblasts prevented mitochondrial targeting of p53 and autophagic cell death. These data provide the first evidence for the dual regulation of autophagic cell death of cardiac myocytes by p53 that is mutually dependent on Bnip3 activation. Hence, our findings may explain how autophagy and cell death are dually regulated during cardiac stress conditions where p53 is activated.
p53, Bnip3, autophagy, cell death, cardiac myocytes
Wang Y, Gang H, Aviv Y, Dhingra R, Margulets V, and Kirshenbaum LA. p53 Mediates Autophagy and Cell Death by a Mechanism Contingent Upon Bnip3. Hypertension. 62:70-77; 2013.