Light-evoked activity and BDNF regulate mitochondrial dynamics and mitochondrial localized translation in CNS axons

Mitochondria coordinate well-described maintenance functions within neuronal axons and dendrites. However, less is known about how mitochondria are regulated during axon development and maturation. Here, we demonstrate that within the developing visual system, retinal ganglion cell (RGC) axons in the retina and optic nerve exhibit increases in mitochondria size, number, and total area in vivo. Our findings indicate that these developmental changes in mitochondria are driven by neuronal activity associated with eye opening and by brain-derived neurotrophic factor (BDNF). These events occur in concert with downstream gene and protein expression changes consistent with mitochondrial biogenesis and energetics pathways. We further demonstrate that activity- and BDNF-regulated transcripts are localized and translated at mitochondria within RGC axons in vivo, concomitant with the regulation of mitochondrial dynamics. These data highlight the previously undescribed regulation of mitochondrial dynamics in axonal maturation, dependent on mechanisms involving neuronal activity and neurotrophic factor signaling, coordinated with mitochondrial-localized translation.