Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling

J Neurosci. 2015 Dec 2;35(48):15996-6011. doi: 10.1523/JNEUROSCI.2068-15.2015.


It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca(2+). Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca(2+)-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca(2+) in astrocytic processes. Thus, the regulation of intracellular Ca(2+) signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca(2+) wave propagation, gliotransmission, and ultimately neuronal function.

Keywords: Miro; NMDARs; astrocyte; calcium; mitochondria; mobility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / ultrastructure*
  • Calcium Signaling / physiology*
  • Cells, Cultured
  • Dependovirus / genetics
  • Embryo, Mammalian
  • Excitatory Amino Acid Agents / pharmacology
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutamic Acid / pharmacology
  • Hippocampus / cytology
  • In Vitro Techniques
  • Intracellular Space / genetics
  • Intracellular Space / metabolism*
  • Male
  • Mitochondria / physiology*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Neurons / physiology
  • Organ Culture Techniques
  • Protein Transport / drug effects
  • Protein Transport / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / physiology*
  • Vesicular Glutamate Transport Protein 1 / metabolism
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*


  • Excitatory Amino Acid Agents
  • Glial Fibrillary Acidic Protein
  • Mitochondrial Proteins
  • Vesicular Glutamate Transport Protein 1
  • Glutamic Acid
  • Rhot1 protein, rat
  • rho GTP-Binding Proteins