Mitochondria-assisted transport of mRNAs along axons

Neurons extend axons over long distances to form unique sites with specific functions. Proper mitochondrial activities are critical for supplying energy to these distant sites. Previous studies detected mRNAs encoding mitochondrial proteins at distant axonal sites, suggesting that localized translation is important for mitochondria functionality. However, the mechanism in which these mRNAs are localized to these distant sites are unknown. We found by fractionation analysis that mitochondria from a neuronal cell line or from motor neuron axons are associated with mRNAs encoding mitochondria proteins. Moreover, in vivo imaging of MS2-tagged mRNAs revealed their co-transport with mitochondria along axons. The coding region, and in particular the mitochondrial targeting sequence (MTS) appeared key for co-transport. Forced transport of mitochondria by Rapalog-induced heterodimerization further substantiated the role of a translational process in co-transport. These results reveal a novel, cotranslational transport mode of mRNAs with moving mitochondria. We propose that organelle-assisted transport of mRNAs is an abundant shuttling mechanism with important implications to cellular physiology.