title: Mitochondria Localize to Injured Axons to Support Regeneration.
abstract: 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.
authors.affiliation: Departments of Genetics and Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Han
authors.affiliation: Departments of Genetics and Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Huma S
authors.initials: HS
authors.lastname: Baig
authors.affiliation: Departments of Genetics and Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. Electronic address: marc.hammarlund@yale.edu.
authors.forename: Marc
authors.initials: M
authors.lastname: Hammarlund
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D001692:Biological Transport; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009416:Nerve Regeneration; D012038:Regeneration
chemical_list: D029742:Caenorhabditis elegans Proteins; D000255:Adenosine Triphosphate; D020928:Mitogen-Activated Protein Kinases; C498050:DLK-1 protein, C elegans; D020930:MAP Kinase Kinase Kinases
keywords: C. elegans; DLK-1; MIRO; axon regeneration; mitochondria