Retrograde mitochondrial transport is required for mitochondrial biogenesis in zebrafish neurons

To maintain a functional mitochondrial population in a long-lived cell like a neuron, mitochondria must be continuously replenished through the process of mitochondrial biogenesis. Because most mitochondrial proteins are nuclear encoded, mitochondrial biogenesis requires communication between mitochondria and the nucleus. This can be a challenge in a large, compartmentalized cell like a neuron in which a significant portion of the mitochondrial population is in neuronal compartments far from the nucleus. Using in vivo assessments of mitochondrial biogenesis in zebrafish neurons, we determined that mitochondrial transport between distal axonal compartments and the cell body is required for sustained mitochondrial biogenesis. Estrogen-related receptor transcriptional activation links transport with nuclear expression of mitochondrial genes. Together, our data support a role for retrograde feedback between axonal mitochondria and the nucleus for regulation of mitochondrial biogenesis in neurons. Lang et al. use larval zebrafish neurons to show that the axonal retrograde transport of mitochondria is required to activate mitochondrial biogenesis through NAD + /Sirt1/Estrogen-related receptor mediated nuclear transcription of mitochondrial genes.