MiR-34a regulates blood-brain barrier permeability and mitochondrial function by targeting cytochrome c

J Cereb Blood Flow Metab. 2016 Feb;36(2):387-92. doi: 10.1177/0271678X15606147. Epub 2015 Sep 30.


The blood-brain barrier is composed of cerebrovascular endothelial cells and tight junctions, and maintaining its integrity is crucial for the homeostasis of the neuronal environment. Recently, we discovered that mitochondria play a critical role in maintaining blood-brain barrier integrity. We report for the first time a novel mechanism underlying blood-brain barrier integrity: miR-34a mediated regulation of blood-brain barrier through a mitochondrial mechanism. Bioinformatics analysis suggests miR-34a targets several mitochondria-associated gene candidates. We demonstrated that miR-34a triggers the breakdown of blood-brain barrier in cerebrovascular endothelial cell monolayer in vitro, paralleled by reduction of mitochondrial oxidative phosphorylation and adenosine triphosphate production, and decreased cytochrome c levels.

Keywords: Blood–brain barrier; cerebrovascular endothelial cells; cytochrome c; mir-34a; mitochondria.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Diphosphate / biosynthesis
  • Animals
  • Blood-Brain Barrier / physiology*
  • Cerebrovascular Circulation / genetics
  • Cerebrovascular Circulation / physiology
  • Computational Biology
  • Cytochromes c / genetics*
  • Cytochromes c / physiology*
  • Endothelial Cells
  • Endothelium, Vascular / cytology
  • Kinetics
  • Mice
  • MicroRNAs / genetics*
  • Mitochondria / genetics*
  • Mitochondria / physiology*
  • Oxidative Phosphorylation
  • Oxygen Consumption / physiology
  • Permeability
  • Tight Junctions


  • MIRN34a microRNA, mouse
  • MicroRNAs
  • Adenosine Diphosphate
  • Cytochromes c