Mitochondrial volume fraction and translation duration impact mitochondrial mRNA localization and protein synthesis
Tatsuhisa Tsuboi, Matheus P. Viana, Fan Xu, Jingwen Yu, Raghav Chanchani, Ximena Garcia Arceo, Evelina Tutucci, Joonhyuk Choi, Yang S. Chen, Robert H. Singer, Susanne M. Rafelski, Brian M. Zid
Abstract
Mitochondria are dynamic organelles that must precisely control their protein composition according to cellular energy demand. Although nuclear-encoded mRNAs can be localized to the mitochondrial surface, the importance of this localization is unclear. As yeast switch to respiratory metabolism, there is an increase in the fraction of the cytoplasm that is mitochondrial. Our data point to this change in mitochondrial volume fraction increasing the localization of certain nuclear-encoded mRNAs to the surface of the mitochondria. 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 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.