Document Detail

miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1.
MedLine Citation:
PMID:  21186368     Owner:  NLM     Status:  MEDLINE    
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.
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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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-26
Journal Detail:
Title:  Nature medicine     Volume:  17     ISSN:  1546-170X     ISO Abbreviation:  Nat. Med.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-10     Completed Date:  2011-02-25     Revised Date:  2011-02-28    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  71-8     Citation Subset:  IM    
Division of Cardiovascular Research, National Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
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MeSH Terms
Base Sequence
Calcineurin / physiology*
GTP Phosphohydrolases / genetics,  physiology*
Mice, Transgenic
MicroRNAs / physiology*,  therapeutic use
Microtubule-Associated Proteins / genetics,  physiology*
Mitochondria / physiology*
Mitochondria, Heart / physiology
Mitochondrial Proteins / genetics,  physiology*
Myocardial Infarction / drug therapy
Reperfusion Injury / drug therapy
Sequence Alignment
Transcription, Genetic
Tumor Suppressor Protein p53 / physiology*
Ventricular Remodeling / drug effects
Reg. No./Substance:
0/MIRN499 microRNA, human; 0/MicroRNAs; 0/Microtubule-Associated Proteins; 0/Mitochondrial Proteins; 0/Tumor Suppressor Protein p53; EC; EC 3.6.1.-/GTP Phosphohydrolases; EC protein, human
Comment In:
Nat Rev Drug Discov. 2011 Feb;10(2):98   [PMID:  21283101 ]

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