mRNAs and mitochondria co-transport to distant neuronal sites

Mitochondria are enriched in neuronal areas with high energy demands, such as synaptic nerve terminals and axon branches, and have essential roles in neuronal function. The protein content of these distant mitochondria needs to be continuously renewed to maintain their proper function. It is hypothesized that these distant mitochondria rely on local translation of nuclear-encoded mRNAs for their maintenance. Accordingly, mRNAs, ribosomes and translation factors need to be transported to neuronal extremities to allow such local synthesis. The mechanisms of transport of these elements is unknown. We propose that transport of these elements occurs through association with moving mitochondria.

Here we show by biochemical fractionation that mRNAs of nuclear-encoded mitochondrial genes are associated with mitochondria, in both neural-like cell line and motor neuron axons. Furthermore, by applying the MS2 mRNA visualization system we show that these mRNAs not only associate but are also co-transported with mitochondria along axons. We tested the importance of different Cox7c mRNA regions and found that the coding sequence has a much greater contribution for localization than its 3`UTR. Specifically, the predicted N-terminal 15 amino acids mitochondrial targeting sequence (MTS) is important for localization. These results reveal that mRNAs encoding mitochondrial proteins are associated and transported with mitochondria in a manner that might involve translation.