Novel Mechanisms of Increased Vulnerability to Ischemia/Reperfusion Injury in Diabetic Myocardium: Role of PTEN-Induced Putative Protein Kinase 1 (PINK1) Deficiency-Induced Mitophagy Impairment

ABSTRACT: Evidence from both animal experiments and clinical studies have shown an increased vulnerability of diabetic hearts to myocardial ischemia/reperfusion injury (MI/RI), but the underlying mechanisms remain unknown. Mitophagy, an important mitochondrial quality control mechanism to clear damaged mitochondria, is mediated by a pathway consisting of PTEN-induced putative protein kinase 1 (PINK1) and the E3 ubiquitin ligase parkin in mammals. Diminished mitophagy due to PINK1 deficiency induces apoptosis and promotes cell death. Our preliminary data showed that PINK1 was down-regulated in H9C2 cardiomyoblasts stimulated by high glucose and high fat. Therefore, we hypothesize that the expression of PINK1 may be reduced in diabetic hearts, which leads to impaired mitophagy and consequently increased myocardium vulnerability to MI/RI.

Keywords: Diabetes Complications, Mitochondria, Myocardial Reperfusion Injury