Local translation of mtIF3 regulates mitochondrial translation for axonal growth

Abstract

Mitochondrial initiation factor 3 (mtIF3) is required for the initiation of mitochondrial translation to dissociate mitochondrial ribosomes by binding to their small subunit. Subsequently, mtIF2, mRNA, and N-formylmethionine-tRNA are positioning in the mtIF3-small subunit complex, which allows the formation of mitochondrial translation initiation complex. Recently, it has been shown that mRNA of nuclear-encoded mtIF3 gene is transported into axonal growth cones. However, biological roles of this mRNA transcript in axonal growth cones remain unknown. Here, we show that mRNA transcript of mtIF3 is locally translated in axonal growth cones upon brain-derived neurotrophic factor (BDNF) treatment and mtIF3 protein is incorporated into mitochondria. mtIF3 then promotes mitochondrial translation that is visualized by our newly developed bimolecular fluorescence complementation (BiFC) method for the ribosomal assembly during mitochondrial translation. We further demonstrate that mtIF3-dependent mitochondrial translation in axon growth cone is essential for axonal extension. Together, these findings provide new insights into the molecular mechanisms of mitochondrial translation in neurons.