Regulation of axonal mitochondrial transport and its impact on synaptic transmission

Mitochondria are essential organelles for neuronal survival and play important roles in ATP generation, calcium buffering, and apoptotic signaling. Due to their extreme polarity, neurons utilize specialized mechanisms to regulate mitochondrial transport and retention along axons and near synaptic terminals where energy supply and calcium homeostasis are in high demand. Axonal mitochondria undergo saltatory and bidirectional movement and display complex mobility patterns. In cultured neurons, approximately one-third of axonal mitochondria are mobile, while the rest remain stationary. Stationary mitochondria at synapses serve as local energy stations that produce ATP to support synaptic function. In addition, axonal mitochondria maintain local Ca²+ homeostasis at presynaptic boutons. The balance between mobile and stationary mitochondria is dynamic and responds quickly to changes in axonal and synaptic physiology. The coordination of mitochondrial mobility and synaptic activity is crucial for neuronal function synaptic plasticity. In this update article, we introduce recent advances in our understanding of the motor-adaptor complexes and docking machinery that mediate mitochondrial transport and axonal distribution. We will also discuss the molecular mechanisms underlying the complex mobility patterns of axonal mitochondria and how mitochondrial mobility impacts the physiology and function of synapses.