Abstract 12925: Mir-761 Regulates Mitochondrial Dynamics and Apoptosis in the Heart
Myocardial infarction is a great threat for health worldwide. It is important to find out the molecular mechanism leading to cardiac apoptosis and the resulting myocardial infarction. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by inhibiting target mRNA translation or promoting mRNA degradation. Mitochondria are dynamic organelles that constantly undergo fission and fusion. The balance between fission and fusion determines the fate of the cells. It remains largely unknown as to how miRNAs regulate mitochondrial dynamics and apoptosis. In this study, we show that mitochondrial fission factor (MFF) is up-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Knockdown of MFF attenuated hydrogen peroxide- and I/R injury-induced mitochondrial fission. Concomitantly, cardiomyocyte apoptosis and myocardial infarction were reduced upon knockdown of MFF. In exploring the molecular mechanism by which MFF is upregulated under the pathological condition, we found that MFF is a direct target of miR-761. Enforced expression of miR-761 led to a reduction of MFF levels. Administration of miR-761 antagomir could elevate the expression of MFF. The luciferase assay showed that miR-761 influenced the translation of MFF. miR-761 inhibited mitochondrial fission and cardiomyocyte apoptosis through repressing MFF. miR-761 mimics significantly reduced infarct sizes and ameliorated cardiac function upon I/R injury. Our present study reveals a novel regulating model of mitochondrial fission which is composed of miR-761 and MFF. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction.
- © 2013 by American Heart Association, Inc.