Axonal mitochondria are essential for the function and survival of neurons. Most mitochondrial proteins are encoded in the nucleus, so their replenishment or modulation in response to cellular needs require their time-consuming translation and transport from the distant cell soma into the axon. Some nuclear-encoded mRNAs are locally translated in distant mitochondria and transported there via RNA granules or through association with endosomes that are delivered into the vicinity of mitochondria. Interestingly, mRNAs encoding mitochondrial proteins have also been found at axonal mitochondria, and in this work, Yoav Arava, Eran Perlson and colleagues (Cohen et al., 2022) thus investigate whether certain mRNAs are transported with mitochondria to axons. Indeed, they show here that the mRNA encoding cytochrome c oxidase subunit 7C (Cox7c), but not other mRNAs that encode non-mitochondrial proteins, associates with mitochondria from primary motor neurons and a neuronal cell line, and is co-transported with them over significant distances, as observed by live imaging. Importantly, the coding region of the Cox7c mRNA is important for its mitochondria-mediated transport, rather than the 3′-UTR, which is involved in other means of axonal mRNA localisation. Taken together, this work thus provides evidence for a role of mRNA trafficking by motile mitochondria in the spatial regulation of the axonal proteome.
