Abstract P1036: Role Of Mitochondrial Ribosomal Protein L7/l12 (mrpl12) In Diabetic Ischemic Heart Disease

Myocardial infarction (MI) is a significant cause of death in diabetic patients. In addition, growing evidence suggests that mitochondrial dysfunction contributes to heart failure in diabetes. However, the molecular mechanisms of mitochondrial dysfunction mediating heart failure in diabetes are still poorly understood. The current study aimed to investigate the role of mitochondrial ribosomal protein L7/L12 (MRPL12) in mouse models of type II diabetes (db/db mice)and high-fat diet (HFD) mice with or without induction of MI and human hearts with or without diabetes (n=7) .Data analysis revealed an increase in MRPL12 levels in the LV tissue of HFD fed mice with MI than in LV tissues of low-fat diet-fed mice with MI, whereas MRPL12 levels remained unchanged in the db/db mice with MI. Intriguingly, we found increased MRPL12 levels in atrial appendage tissue of diabetic patients with ischemic heart disease compared to non-diabetic patients. We utilized human cardiomyocyte cell-line (AC-16) as surrogate models to delineate the mechanisms; surprisingly, adenovirus-mediated overexpression of MRPL12 with or without hyperglycemia in AC-16 cardiomyocytes does not affect mitochondrial OXPHOS . In addition, overexpression of MRPL12 had no effect on the mitochondrial ROS, mitochondrial membrane depolarization, and caspase activity in AC-16 cardiomyocytes. Whereas RNA interference (RNAi)-mediated MRPL12 silencing remarkedly reduced mitochondrial oxidative phosphorylation in AC-16 cells without any stress. In addition, knockdown of MRPL12 increased mitochondrial membrane depolarization mitochondrial ROS and reduced maximal respiratory capacity of mitochondria without any stress. Overall, our results provide new insights into the role of MRPL12 in the pathophysiology of MI in diabetes.