Regulation of Synaptic Transmission through Mitochondrial Positioning and Metabolism

Abstract This chapter provides an overview of axonal mitochondrial trafficking/anchoring and their metabolic function in modulating synaptic efficacy and plasticity. Synaptic transmission is a key neuronal information process. Mitochondria are commonly localized at presynaptic terminals, where they sustain presynaptic function by producing ATP and buffering calcium. Given their extremely polarized geometry, neurons face exceptional challenges maintaining local ATP and Ca2+ homeostasis at distal presynapses that are constantly changing with altered synaptic activity. Mitochondrial transport in axons and their distribution at presynapses are correlated with synaptic activity. Therefore, precise control of axonal mitochondrial trafficking and positioning and their capacity in buffering calcium and supplying presynaptic energy or “synaptoenergetics” are critical for neurons to adapt to dynamic synaptic activity. Mitochondrial dysfunction and impaired trafficking have been implicated in major neurological disorders associated with bioenergetic failure. Investigation into the roles of mitochondria in synaptic transmission is an important research frontier.