| First Author | Shimizu Y | Year | 2016 |
| Journal | J Mol Cell Cardiol | Volume | 97 |
| Pages | 56-66 | PubMed ID | 27108530 |
| Mgi Jnum | J:250832 | Mgi Id | MGI:6102215 |
| Doi | 10.1016/j.yjmcc.2016.04.008 | Citation | Shimizu Y, et al. (2016) DJ-1 protects the heart against ischemia-reperfusion injury by regulating mitochondrial fission. J Mol Cell Cardiol 97:56-66 |
| abstractText | Recent data indicates that DJ-1 plays a role in the cellular response to stress. Here, we aimed to examine the underlying molecular mechanisms mediating the actions of DJ-1 in the heart following myocardial ischemia-reperfusion (I/R) injury. In response to I/R injury, DJ-1 KO mice displayed increased areas of infarction and worsened left ventricular function when compared to WT mice, confirming a protective role for DJ-1 in the heart. In an effort to evaluate the potential mechanism(s) responsible for the increased injury in DJ-1 KO mice, we focused on SUMOylation, a post-translational modification process that regulates various aspects of protein function. DJ-1 KO hearts after I/R injury were found to display enhanced accumulation of SUMO-1 modified proteins and reduced SUMO-2/3 modified proteins. Further analysis, revealed that the protein expression of the de-SUMOylation enzyme SENP1 was reduced, whereas the expression of SENP5 was enhanced in DJ-1 KO hearts after I/R injury. Finally, DJ-1 KO hearts were found to display enhanced SUMO-1 modification of dynamin-related protein 1, excessive mitochondrial fission, and dysfunctional mitochondria. Our data demonstrates that the activation of DJ-1 in response to myocardial I/R injury protects the heart by regulating the SUMOylation status of Drp1 and attenuating excessive mitochondrial fission. |
