Mitochondrial dynamics in CNS health and disease

The tight regulation of mitochondrial transport and anchoring in brain cells is essential for providing ATP at the correct spatial location to power neural function and computation, and for providing calcium buffering at sites of calcium entry or release.

Using a multidisciplinary approach, combining imaging, biochemistry, electrophysiology and mouse transgenics we will determine the molecular and cellular mechanisms by which the cytoskeleton coordinates mitochondrial transport, localisation and remodelling in neurons and glial cells.

The influence of this regulation on the development and maintenance of neuronal connectivity, function, plasticity and pathology will then be determined in vitro and in vivo.

The main objectives are to define (i) the role of Miro proteins as central coordinators of the activity-dependent transport, positioning and remodelling of mitochondria through the microtubule, actin and septin cytoskeletons; (ii) how mitochondrial position and calcium buffering in neurons and glia impacts the formation, maintenance and plasticity of synapses; and (iii) the mechanisms by which disrupted mitochondrial dynamics lead to neuronal pathology and neurodegeneration.

Our proposal will provide unique insight into how mitochondrial networks in neurons and astrocytes contribute to regulating the operation and plasticity of synapses and how their disruption leads to neuronal pathology in brain diseases.