Local translation of ATP synthase subunit 9 mRNA alters ATP levels and the production of ROS in the axon.
To date, it has been demonstrated that axonal mRNA populations contain a large number of nuclear-encoded mRNAs for mitochondrial proteins. Here, we report that the mRNA encoding ATP synthase subunit 9 (ATP5G1), a key component of Complex V of the oxidative phosphorylation chain, is present in the axons of rat primary sympathetic neurons, as judged by in situ hybridization and qRT-PCR methodology. Results of metabolic labeling studies establish that this nuclear-encoded mRNA is translated in the axon. The siRNA-mediated knock-down of axonal ATP5G1 mRNA resulted in a significant reduction of axonal ATP5G1 protein and ATP levels. Silencing of local ATP5G1 expression enhanced the production of local reactive oxygen species (ROS). Importantly, reduction in the levels of ATP5G1 expression resulted in a marked attenuation in the rate of elongation of the axon. Exposure of the distal axons to nordihydroguaiaretic acid (NDGA), a ROS scavenger, mitigated the reduction in the rate of axon elongation observed after knock-down of ATP5G1. Taken together, these data call attention to the key regulatory role that local translation of nuclear-encoded mitochondrial mRNAs plays in energy metabolism and growth of the axon.
Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1381, USA.
Orlangie
O
Natera-Naranjo
Amar N
AN
Kar
Armaz
A
Aschrafi
Noreen M
NM
Gervasi
Margaret A
MA
Macgibeny
Anthony E
AE
Gioio
Barry B
BB
Kaplan
D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; C573472:ATP synthase subunit 9, rat; D025261:Mitochondrial Proton-Translocating ATPases