title: The axon-protective WLD(S) protein partially rescues mitochondrial respiration and glycolysis after axonal injury.
abstract: The axon-protective Wallerian degeneration slow (WLD(S)) protein can ameliorate the decline in axonal ATP levels after neurite transection. Here, we tested the hypothesis that this effect is associated with maintenance of mitochondrial respiration and/or glycolysis. We used isolated neurites of superior cervical ganglion (SCG) cultures in the Seahorse XF-24 Metabolic Flux Analyser to determine mitochondrial respiration and glycolysis under different conditions. We observed that both mitochondrial respiration and glycolysis declined significantly during the latent phase of Wallerian degeneration. WLD(S) partially reduced the decline both in glycolysis and in mitochondrial respiration. In addition, we found that depleting NAD levels in uncut cultures led to changes in mitochondrial respiration and glycolysis similar to those rescued by WLD(S) after cut, suggesting that the maintenance of NAD levels in Wld(S) neurites after axonal injury at least partially underlies the maintenance of ATP levels. However, by using another axon-protective mutation (Sarm1(-/-)), we could demonstrate that rescue of basal ECAR (and hence probably glycolysis) rather than basal OCR (mitochondrial respiration) may be part of the protective phenotype to delay Wallerian degeneration. These findings open new routes to study glycolysis and the connection between NAD and ATP levels in axon degeneration, which may help to eventually develop therapeutic strategies to treat neurodegenerative diseases.
authors.affiliation: The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
authors.forename: Katharina
authors.initials: K
authors.lastname: Godzik
authors.forename: Michael P
authors.initials: MP
authors.lastname: Coleman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D019069:Cell Respiration; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000166:cytology
chemical_list: D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C543961:SARM1 protein, mouse; C442580:Wld protein, mouse; D000255:Adenosine Triphosphate