miR-761 regulates the mitochondrial network by targeting mitochondrial fission factor

Free Radic Biol Med. 2013 Dec:65:371-379. doi: 10.1016/j.freeradbiomed.2013.07.009. Epub 2013 Jul 15.

Abstract

Mitochondria are dynamic organelles that constantly undergo fission and fusion. The balance between fission and fusion determines the fate of the cell. In this study, we show that mitochondrial fission factor (MFF) is upregulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Knockdown of MFF attenuated hydrogen peroxide- and I/R injury-induced cardiomyocyte apoptosis and myocardial infarction. We found that MFF is a direct target of miR-761, and miR-761 inhibits mitochondrial fission and cardiomyocyte apoptosis by repressing MFF. This study reveals a novel model of mitochondrial fission regulation, which is composed of miR-761 and MFF. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction.

Keywords: Apoptosis; Free radicals; Hydrogen peroxide; Ischemia/reperfusion; MFF; MicroRNAs; Mitochondrial fission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Immunoblotting
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Microscopy, Electron, Transmission
  • Mitochondrial Dynamics / physiology*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Myocytes, Cardiac / metabolism
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • MIRN761 microRNA, mouse
  • MIRN761 microRNA, rat
  • MicroRNAs
  • Mitochondrial Proteins