Axon viability and mitochondrial function are dependent on local protein synthesis in sympathetic neurons.
(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.
Hillefors
Mi
M
Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1381, USA.
Gioio
Anthony E
AE
Mameza
Marie G
MG
Kaplan
Barry B
BB
D000255:Adenosine Triphosphate / Q000378:metabolism; D000320:Adrenergic Fibers / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D018929:Cell Culture Techniques / Q000295:instrumentation; D002470:Cell Survival; D002478:Cells, Cultured; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D000255:Adenosine Triphosphate