@article{7989695ceade423e8eb0a2db1643f7a5,
title = "Mitochondrial volume fraction and translation duration impact mitochondrial mRNA localization and protein synthesis",
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.",
author = "Tatsuhisa Tsuboi and Viana, {Matheus P.} and Fan Xu and Jingwen Yu and Raghav Chanchani and Arceo, {Ximena G.} and Evelina Tutucci and Joonhyuk Choi and Chen, {Yang S.} and Singer, {Robert H.} and Rafelski, {Susanne M.} and Zid, {Brian M.}",
note = "Funding Information: We thank members of the Zid laboratory as well as T Endo, S Iwasaki, G Goshima, E Koslover, W Wang and V Bilanchone for helpful discussions and A Subramaniam and S Mukherji for feedback on the paper. Receipt of the MS2-tagging plasmids and yeast-optimized fluorophore plasmids from Dr. J Gerst and Dr. K Thorn is gratefully acknowledged. We thank M Zid, A Guzikowski and V Harjono for critically reading the manuscript. This work was supported in part by National Institutes of Health GM57071 (to RHS), startup funds from UCI, NSF grant MCB-1330451 and Ellison Medical Foundation (to SMR), startup funds from UCSD and from the National Institutes of Health R35GM128798 (to BMZ), and NINDS P30NS047101 (to UCSD microscopy Core). ET was supported by Swiss National Science Foundation Fellowships P2GEP3_155692 and P300PA_164717. TT acknowledges support from a Japan Society for the Promotion of Science (JSPS) for a research abroad fellowship and postdoctoral fellowship (18J00995), and Uehara Memorial Foundation for research abroad fellowship.Japan Society for the Promotion Research abroad fellowship Tatsuhisa Tsuboi of Science Japan Society for the Promotion 18J00995 Tatsuhisa Tsuboi of Science Uehara Memorial Foundation Research abroad fellowship Tatsuhisa Tsuboi National Institute of General R35GM128798 Brian M Zid Medical Sciences National Science Foundation MCB-1330451 Susanne M Rafelski Ellison Medical Foundation New Scholar Award In Susanne M Rafelski Aging National Institute of General GM57071 Robert H Singer Medical Sciences Swiss National Science Foundation Fellowship P2GEP3_155692 Evelina Tutucci Swiss National Science Foundation Fellowship P300PA_164717 Evelina Tutucci. Funding Information: We thank members of the Zid laboratory as well as T Endo, S Iwasaki, G Goshima, E Koslover, W Wang and V Bilanchone for helpful discussions and A Subramaniam and S Mukherji for feedback on the paper. Receipt of the MS2-tagging plasmids and yeast-optimized fluorophore plasmids from Dr. J Gerst and Dr. K Thorn is gratefully acknowledged. We thank M Zid, A Guzikowski and V Harjono for critically reading the manuscript. This work was supported in part by National Institutes of Health GM57071 (to RHS), startup funds from UCI, NSF grant MCB-1330451 and Ellison Medical Foundation (to SMR), startup funds from UCSD and from the National Institutes of Health R35GM128798 (to BMZ), and NINDS P30NS047101 (to UCSD microscopy Core). ET was supported by Swiss National Science Foundation Fellowships P2GEP3_155692 and P300PA_164717. TT acknowledges support from a Japan Society for the Promotion of Science (JSPS) for a research abroad fellowship and postdoctoral fellowship (18J00995), and Uehara Memorial Foundation for research abroad fellowship. Publisher Copyright: {\textcopyright} Tsuboi et al.",
year = "2020",
month = aug,
doi = "10.7554/ELIFE.57814",
language = "English (US)",
volume = "9",
pages = "1--24",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}