论文题目: | miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1 |
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作者: | Jian-Xun Wang, Jian-Qin Jiao, Qian Li, Bo Long, Kun Wang, Jin-Ping Liu, Yan-Rui Li, Pei-Feng Li |
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年: | 2011 |
卷: | 71 |
期: | 1 |
页: | 71-78 |
联系作者: | 李培峰 |
发表期刊: | Nature Medicine |
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论文连接 | http://www.nature.com/nm/journal/v17/n1/full/nm.2282.html |
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摘要: | 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 α- and β-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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