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Title: The spatial regulation of astrocyte mitochondria by Miro1
Author: Stephen, T.-L.
ISNI:       0000 0004 7659 4490
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Mitochondria are energy generating organelles important for regulating the levels of Ca2+ inside cells. In terms of astrocytes, intracellular Ca2+ is crucial for many aspects of their signalling and for regulating their release of molecules that can profoundly modulate neuronal signalling. In addition, astrocytes take up potentially harmful molecules to prevent neuronal damage, a process that is energetically demanding. Therefore, it is expected that effective spatiotemporal provision of energy and Ca2+ buffering, by mitochondria, is important in astrocytes. In this thesis, a mechanism is proposed for the spatial regulation of mitochondria within the processes of astrocytes involving the EF-hand Ca2+-sensing motifs of the Mitochondrial Rho- GTPase protein, Miro1. Live-cell confocal microscopy of rat organotypic hippocampal slices, revealed that enhancing neuronal activity induces transient mitochondrial remodelling in astrocytes alongside a reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca2+. Stimulating neuronal activity also induces mitochondrial confinement within astrocytic processes close to synapses. Furthermore, the Ca2+-sensing EF-hands of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for their confinement near synapses. Additionally, activity-dependent mitochondrial positioning, by Miro1, reciprocally regulates intracellular Ca2+ signalling within astrocytes. Disrupting the regulation of astrocyte intracellular Ca2+, by Miro1, reduces the number of excitatory synapses, potentially though elevated gliotransmission. These results suggest that the spatial regulation of mitochondria in astrocytes is not only important for astrocyte communication and gliotransmission, but also for maintaining the function of surrounding neurons.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available