Abstract 3593: Mir-30 Regulates Mitochondrial Fission in Cardiomyocytes
Apoptosis is involved in cardiac diseases such as myocardial infarction, cardiomyopathy and heart failure. MicroRNAs (miRNAs) participate in the regulation of apoptosis. However, it remains largely unknown as to how miRNAs are integrated into the apoptotic program. Mitochondrial fission is involved in the initiation of apoptosis. It is not yet clear whether miRNAs are able to regulate mitochondrial fission. Our present work aimed at delineating the molecular mechanism by which mitochondrial fission is regulated in cardiomyocytes. Our data show that miR-30 family members can inhibit mitochondrial fission and the consequent apoptosis in cardiomyocytes induced by reactive oxygen species. In exploring the underlying molecular mechanism, we identified that miR-30 family members can suppress p53 expression. In response to the treatment with reactive oxygen species, the expression levels of miR-30 family members were reduced, whereas p53 was upregulated. p53 transcriptionally activated the mitochondrial fission protein, dynamin-related protein-1 (Drp1). The latter conveyed the apoptotic signal of p53 by initiating mitochondrial fission program. miR-30 family members inhibited mitochondrial fission through suppressing the expression of p53 and its downstream target Drp1. Our data reveal a novel model in which a miRNA can regulate cardiomyocyte apoptosis through targeting the mitochondrial fission machinery.
This research has received full or partial funding support from the American Heart Association, National Center.