miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1

Citation metadata

Date: Jan. 2011
From: Nature Medicine(Vol. 17, Issue 1)
Publisher: Nature Publishing Group
Document Type: Report
Length: 5,585 words
Lexile Measure: 1330L

Document controls

Main content

Abstract :

Myocardial infarction is a leading cause of mortality worldwide. Here we report that modulation of microRNA-499 (miR-499) levels affects apoptosis and the severity of myocardial infarction and cardiac dysfunction induced by ischemia-reperfusion. We found that both the [alpha]- and [beta]-isoforms of the calcineurin catalytic subunit are direct targets of miR-499 and that miR-499 inhibits cardiomyocyte apoptosis through its suppression of calcineurin-mediated dephosphorylation of dynamin-related protein-1 (Drp1), thereby decreasing Drp1 accumulation in mitochondria and Drp1-mediated activation of the mitochondrial fission program. We also found that p53 transcriptionally downregulates miR-499 expression. Our data reveal a role for miR-499 in regulating the mitochondrial fission machinery and we suggest that modulation of miR-499 levels may provide a therapeutic approach for treating myocardial infarction.

Source Citation

Source Citation   

Gale Document Number: GALE|A246715414