Mitochondria Localize to Injured Axons to Support Regeneration

Axon regeneration is essential to restore the nervous system after axon injury. However, the neuronal cell biology that underlies axon regeneration is incompletely understood. Here we use in vivo, single-neuron analysis to investigate the relationship between nerve injury, mitochondrial localization, and axon regeneration. Mitochondria translocate into injured axons so that average mitochondria density increases after injury. Moreover, single-neuron analysis reveals that axons that fail to increase mitochondria have poor regeneration. Experimental alterations to axonal mitochondrial distribution or mitochondrial respiratory chain function result in corresponding changes to regeneration outcomes. Axonal mitochondria are specifically required for growth-cone migration, identifying a key energy challenge for injured neurons. Finally, mitochondrial localization to the axon after injury is regulated in part by dual-leucine zipper kinase 1 (DLK-1), a conserved regulator of axon regeneration. These data identify regulation of axonal mitochondria as a new cell-biological mechanism that helps determine the regenerative response of injured neurons. •Axon injury increases mitochondria flux and axonal mitochondria density•Robust mitochondria density is critical for axon regeneration•Mitochondrial ATP production supports axon regeneration•The DLK-1 MAP kinase pathway regulates axonal mitochondria density Han et al. find that axon injury and activation of DLK-1 MAP kinase increase axonal mitochondria density. Robust mitochondria density is required to produce adequate ATP for axon regeneration.