A heterogeneous population of nuclear-encoded mitochondrial mRNAs is present in the axons of primary sympathetic neurons.
Mitochondria are enriched in subcellular regions of high energy consumption, such as axons and pre-synaptic nerve endings. Accumulating evidence suggests that mitochondrial maintenance in these distal structural/functional domains of the neuron depends on the "in-situ" translation of nuclear-encoded mitochondrial mRNAs. In support of this notion, we recently provided evidence for the axonal targeting of several nuclear-encoded mRNAs, such as cytochrome c oxidase, subunit 4 (COXIV) and ATP synthase, H+ transporting and mitochondrial Fo complex, subunit C1 (ATP5G1). Furthermore, we showed that axonal trafficking and local translation of these mRNAs plays a critical role in the generation of axonal ATP. Using a global gene expression analysis, this study identified a highly diverse population of nuclear-encoded mRNAs that were enriched in the axon and presynaptic nerve terminals. Among this population of mRNAs, fifty seven were found to be at least two-fold more abundant in distal axons, as compared with the parental cell bodies. Gene ontology analysis of the nuclear-encoded mitochondrial mRNAs suggested functions for these gene products in molecular and biological processes, including but not limited to oxidoreductase and electron carrier activity and proton transport. Based on these results, we postulate that local translation of nuclear-encoded mitochondrial mRNAs present in the axons may play an essential role in local energy production and maintenance of mitochondrial function.
Laboratory of Molecular Biology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Armaz
A
Aschrafi
Laboratory of Molecular Biology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Amar N
AN
Kar
Laboratory of Molecular Biology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Jenna R
JR
Gale
Laboratory of Molecular Biology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Abdel G
AG
Elkahloun
Laboratory of Molecular Biology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Jose Noberto S
JN
Vargas
Laboratory of Molecular Biology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Naomi
N
Sales
Laboratory of Molecular Biology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Gabriel
G
Wilson
Laboratory of Molecular Biology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Miranda
M
Tompkins
Laboratory of Molecular Biology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Anthony E
AE
Gioio
Laboratory of Molecular Biology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: kaplanb@mail.nih.gov.
Barry B
BB
Kaplan
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D001692:Biological Transport; D020869:Gene Expression Profiling; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000166:cytology*
D012333:RNA, Messenger; D000255:Adenosine Triphosphate
Campenot cell culture chambers; Microarray analyses; Subcellular localization; Superior cervical ganglion; mRNAs