miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1
Date
2011
Authors
Wang, J.X.
Jiao, J.Q.
Li, Q.
Long, B.
Wang, K.
Liu, J.P.
Li, Y.R.
Li, P.F.
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Journal article
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Nature Medicine, 2011; 17(1):71-78
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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.
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Data source: Supplementary data, http://www.nature.com/nm/journal/v17/n1/extref/nm.2282-S1.pdf
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Copyright 2011 Nature America