Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence
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1-s2.0-S0092867419300510-main.pdf
Description
Published version
Size
4.65 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Neurohr, Gabriel
Terry, Rachel L.
Lengefeld, Jette
Bonney, Megan Ellis
Brittingham, Gregory P.
Moretto, Fabien
Miettinen, Teemu P
Vaites, Laura Pontano
Soares, Luis M.
Paulo, Joao A.
Date Issued
February 2019
Journal
Cell
Publisher
Elsevier BV
Citation
Neurohr, Gabriel E. et al. "Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence." Cell 175, 5 (February 2019): P1083-1097.e18 © 2019 The Author(s)
Version
Final published version
Abstract
Cell size varies greatly between cell types, yet within a specific cell type and growth condition, cell size is narrowly distributed. Why maintenance of a cell-type specific cell size is important remains poorly understood. Here we show that growing budding yeast and primary mammalian cells beyond a certain size impairs gene induction, cell-cycle progression, and cell signaling. These defects are due to the inability of large cells to scale nucleic acid and protein biosynthesis in accordance with cell volume increase, which effectively leads to cytoplasm dilution. We further show that loss of scaling beyond a certain critical size is due to DNA becoming limiting. Based on the observation that senescent cells are large and exhibit many of the phenotypes of large cells, we propose that the range of DNA:cytoplasm ratio that supports optimal cell function is limited and that ratios outside these bounds contribute to aging. Optimal cell function requires maintenance of a narrow range of DNA:cytoplasm ratios and when cell size exceeds this ratio cytoplasmic dilution contributes to senescence
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/j.cell.2019.01.018
