DJ-1 protects the heart against ischemia–reperfusion injury by regulating mitochondrial fission. (August 2016)

• Record Type: Journal Article
• Authors: Shimizu, Yuuki; Lambert, Jonathan P.; Nicholson, Chad K.; Kim, Joshua J.; Wolfson, David W.; Cho, Hee Cheol; Husain, Ahsan; Naqvi, Nawazish; Chin, Li-Shen; Li, Lian; Calvert, John W.
• Is Part Of: Journal of molecular and cellular cardiology. Volume 97(2016:Aug.)
• Page Start: 56
• Page End: 66
• Publication Date: 2016-08
• Subjects: DJ-1 -- Myocardial ischemia -- Mitochondrial fission -- SUMOylation; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2016.04.008
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: 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. Graphical abstract: Highlights: Myocardial ischemia–reperfusion (I/R) injury induces the cleavage of DJ-1. DJ-1 influences protein SUMOylation following myocardial I/R injury. DJ-1 protects against myocardial I/R injury by attenuating mitochondrial fission. DJ-1 alters the expression of SENP5 to influence the SUMO status of Drp1.