Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling
| Autor: | Terri-Leigh, Stephen, Nathalie F, Higgs, David F, Sheehan, Sana, Al Awabdh, Guillermo, López-Doménech, I Lorena, Arancibia-Carcamo, Josef T, Kittler |
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| Rok vydání: | 2015 |
| Předmět: |
Male
rho GTP-Binding Proteins Intracellular Space Glutamic Acid In Vitro Techniques Hippocampus Mitochondrial Proteins Rats Sprague-Dawley Organ Culture Techniques Glial Fibrillary Acidic Protein Animals Calcium Signaling Excitatory Amino Acid Agents Cells Cultured Neurons Articles Dependovirus Embryo Mammalian Mitochondria Rats Protein Transport Animals Newborn Astrocytes Synapses Vesicular Glutamate Transport Protein 1 Female |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 35(48) |
| ISSN: | 1529-2401 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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