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 @entity35 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 @entity141 . Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the @entity141 -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 @entity141 in astrocytic processes. Thus, the regulation of intracellular @entity141 signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte @entity141 wave propagation, gliotransmission, and ultimately neuronal function. SIGNIFICANCE STATEMENT: Mitochondria are key cellular organelles that play important roles in providing cellular energy and buffering intracellular @entity460 ions. The mechanisms that control mitochondrial distribution within the processes of glial cells called astrocytes and the impact this may have on @entity460 signaling remains unclear. We show that activation of @entity3264 receptors or increased neuronal activity leads to the altered transport of mitochondria and their positioning at synapses dependent on a key mitochondrial trafficking protein called Miro1. We also show that, the control of mitochondrial movement and stopping by Miro plays an important role in regulating astrocyte @entity460 responses. Thus the regulation of intracellular @entity460 signaling, by Miro-mediated mitochondrial positioning, could have important consequences for astrocyte signaling and neuron-glial interactions.

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

@entity35 :: ('10116', 'Species') :: ['rat'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity3264 :: ('D018698', 'Chemical') :: ['glutamate'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium']
@entity460 :: (MESH:D002118,Chemical) :: ['Calcium']
