Drp1 stabilizes p53 on the mitochondria to trigger necrosis under oxidative stress conditions, in vitro and in vivo

In this study, we showed that Dynamin-related protein 1 (Drp1), a primary mitochondrial fission protein, stabilizes the well-known stress gene p53 and is required for p53 translocation to the mitochondria under conditions of oxidative stress. We found that Drp1 binding to p53 induced mitochondria-related necrosis. In contrast, inhibition of Drp1 hyperactivation by Drp1 silence RNA reduced necrotic cell death in cell culture exposed to oxidative stress. Most significantly, we demonstrated that inhibition of Drp1 by the Drp1 peptide inhibitor P110, which was recently developed by our group, abolished p53 association with the mitochondria and reduced brain infarction in rats subjected to brain ischemia/reperfusion injury. Taken together, these findings reveal a novel mechanism of Drp1 hyperactivation in the induction of mitochondrial damage and subsequent cell death. We propose that a Drp1 inhibitor such as P110 is a possible therapeutic agent for diseases in which hyperactivated Drp1 contributes to the pathology.

Source: BJ Cell - April 23, 2014 Category: Biochemistry Authors: X Guo, H Sesaki, X Qi Tags: BJ Signal Source Type: research