The bioenergetics of neuronal morphogenesis and regeneration: Frontiers beyond the mitochondrion

The formation of axons and dendrites during development, and their regeneration following injury, are energy intensive processes. The underlying assembly and dynamics of the cytoskeleton, axonal transport mechanisms, and extensive signaling networks all rely on ATP and GTP consumption. Cellular ATP is generated through oxidative phosphorylation (OxP) in mitochondria, glycolysis and "regenerative" kinase systems. Recent investigations have focused on the role of the mitochondrion in axonal development and regeneration emphasizing the importance of this organelle and OxP in axon development and regeneration. In contrast, the understanding of alternative sources of ATP in neuronal morphogenesis and regeneration remains largely unexplored. This review focuses on the current state of the field of neuronal bioenergetics underlying morphogenesis and regeneration and considers the literature on the bioenergetics of non-neuronal cell motility to emphasize the potential contributions of non-mitochondrial energy sources.