Axon Viability and Mitochondrial Function are Dependent on Local Protein Synthesis in Sympathetic Neurons
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(1) Axons contain numerous mRNAs and a local protein synthetic system that can be regulated independently of the cell body. (2) In this study, cultured primary sympathetic neurons were employed, to assess the effect of local protein synthesis blockade on axon viability and mitochondrial function. (3) Inhibition of local protein synthesis reduced newly synthesized axonal proteins by 65% and resulted in axon retraction after 6 h. Acute inhibition of local protein synthesis also resulted in a significant decrease in the membrane potential of axonal mitochondria. Likewise, blockade of local protein transport into the mitochondria by transfection of the axons with Hsp90 C-terminal domain decreased the mitochondrial membrane potential by 65%. Moreover, inhibition of the local protein synthetic system also reduced the ability of mitochondria to restore axonal levels of ATP after KCl-induced depolarization. (4) Taken together, these results indicate that the local protein synthetic system plays an important role in mitochondrial function and the maintenance of the axon.
KeywordsSuperior cervical ganglia Axon Local protein synthesis Mitochondrial membrane potential ATP levels
We thank Dr. J. Young (McGill Faculty of Medicine, Montreal, Quebec, Canada) for providing the C90 plasmid.
- Bauer MF, Hofmann S (2006) Import of mitochondrial proteins. In: Schapira AHV (ed) Mitochondrial function and dysfunction. Academic Press, San Diego, CA, pp 57–90Google Scholar
- Cossarizza A, Baccaranicontri M, Kalashnikova G, Franceschi C (1993) A new method for the cytofluorometric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem Biophys Res Commun 197:40–45PubMedCrossRefGoogle Scholar
- Heales SJR, Gegg ME, Clark JB (2006) Oxidative phosporylation: structure, function, and intermediary metabolism. In: Schapira AHV (ed) Mitochondria function and dysfuntion. Academic Press, San Diego, CA, pp 25–56Google Scholar
- Li C, Sasaki Y, Takei K, Yamamoto H, Shouji M, Sugiyama Y, Kawakami T, Nakamura F, Yagi T, Ohshima T, Goshima Y (2004) Correlation between Semaphorin3A-induced facilitation of axonal transport and local activation of a translation initiation factor eukaryotic translation initiation factor 4E. J Neurosci 24:6161–6170PubMedCrossRefGoogle Scholar