Activity-dependent trafficking of mitochondria to synapses by Miro1. (360G-Wellcome-093239_Z_10_Z)

This proposal will study the mechanisms that control the trafficking of the energy providing mitochondria within neurons, and how this relates to neuronal development and connectivity. Using imaging, molecular and cell biological techniques, combined with mouse transgenic approaches we will determine the molecular mechanisms underlying the activity-dependent subcellular positioning of mitochondria in neurons. We will examine how the mitochondrial calcium-sensing GTPase Miro1 acts as a molecul ar switch to regulate mitochondrial movement and distribution. How Miro1-dependent mitochondrial trafficking regulates neuronal migration and morphogenesis will also be determined in addition to the role of Miro1 in regulating the formation and maintenance of synapses and dendritic spines. A key goal will also be to determine if different roles exist for constitutive versus activity-dependent control of mitochondrial transport by Miro1 in these processes. These studies will significantly adv ance our understanding of the molecular mechanisms that control mitochondrial localisation in neurons and the role that activity-dependent mitochondrial trafficking plays in regulating neuronal morphogenesis and connectivity.