Neuronal mitochondrial dynamics: roles in brain disorders and therapeutic potential

Mitochondrial dynamics - processes that include fission, fusion, transport, and mitophagy - are essential for shaping mitochondrial form and function to meet neuronal homeostatic demands. Growing evidence links imbalances in these processes to the pathogenesis of multiple brain disorders. In this review we comprehensively summarize the molecular mechanisms that govern mitochondrial dynamics and clarify their roles in key neuronal functions, including synaptic transmission, vesicle recycling, and calcium buffering. We also examine how disruptions in mitochondrial dynamics drive synaptic dysfunction and neuronal injury, with specific implications for neurodegenerative and psychiatric disorders. Finally, we evaluate emerging therapeutic strategies that target mitochondrial dynamics - both pharmacological and genetic - and highlight their promise as novel therapies for brain disorders. This synthesis provides an in-depth perspective on mitochondrial dynamics in brain health and disease and aims to guide future research and drug development.