Mitochondrial volume fraction and translation speed impact mRNA localization and production of nuclear-encoded mitochondrial proteins

Mitochondria are dynamic in their size and morphology yet must also precisely control their protein composition according to cellular energy demand. Although nuclear-encoded mRNAs can be localized to the mitochondrial outer membrane, the importance of this localization in altering mitochondrial protein composition is unclear. We have found that, as yeast switch from fermentative to respiratory metabolism, there is an increase in the fraction of the cytoplasm that is mitochondrial. This drives the localization of certain nuclear-encoded mitochondrial mRNAs to the surface of the mitochondria. Through tethering experiments, we show that mitochondrial mRNA localization is necessary and sufficient to increase protein production to levels required during respiratory growth. Furthermore, we find that ribosome stalling impacts mRNA sensitivity to mitochondrial volume fraction and counterintuitively leads to enhanced protein synthesis by increasing mRNA localization to the mitochondria. This points to a mechanism by which cells are able to use translation elongation and the geometric constraints of the cell to fine-tune organelle-specific gene expression through mRNA localization while potentially circumventing the need to directly coordinate with the nuclear genome.