Increasing cell size remodels the proteome and promotes senescence.

Michael C Lanz, Evgeny Zatulovskiy, Matthew P Swaffer, Lichao Zhang, Ilayda Ilerten, Shuyuan Zhang, Dong Shin You, Georgi Marinov, Patrick McAlpine, Joshua E Elias, Jan M Skotheim

Molecular cell 2022 Sep 01

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Cell size is tightly controlled in healthy tissues, but it is unclear how deviations in cell size affect cell physiology. To address this, we measured how the cell's proteome changes with increasing cell size. Size-dependent protein concentration changes are widespread and predicted by subcellular localization, size-dependent mRNA concentrations, and protein turnover. As proliferating cells grow larger, concentration changes typically associated with cellular senescence are increasingly pronounced, suggesting that large size may be a cause rather than just a consequence of cell senescence. Consistent with this hypothesis, larger cells are prone to replicative, DNA-damage-induced, and CDK4/6i-induced senescence. Size-dependent changes to the proteome, including those associated with senescence, are not observed when an increase in cell size is accompanied by an increase in ploidy. Together, our findings show how cell size could impact many aspects of cell physiology by remodeling the proteome and provide a rationale for cell size control and polyploidization. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Michael C Lanz, Evgeny Zatulovskiy, Matthew P Swaffer, Lichao Zhang, Ilayda Ilerten, Shuyuan Zhang, Dong Shin You, Georgi Marinov, Patrick McAlpine, Joshua E Elias, Jan M Skotheim. Increasing cell size remodels the proteome and promotes senescence. Molecular cell. 2022 Sep 01;82(17):3255-3269.e8