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Genome dilution by cell growth drives starvation-like proteome remodeling in yeast and mammalian cells

ABSTRACT: Cell size is tightly controlled in healthy tissues and single-celled organisms, but it remains unclear how cell size influences physiology. Increasing cell size was recently shown to remodel the proteomes of cultured human cells, demonstrating that large and small cells of the same type can be compositionally different. Here, we utilize the natural heterogeneity of hepatocyte ploidy and yeast genetics to establish that ploidy-to-cell size ratio is a highly conserved determinant of proteome composition. In both mammalian and yeast cells, genome dilution by cell growth elicits a starvation-like phenotype, suggesting that growth in large cells is restricted by genome concentration in manner that mimics a limiting nutrient. Moreover, genome dilution explains some proteomic changes ascribed to yeast aging. Overall, our data indicate that genome concentration drives changes in cell composition independently of external environmental cues.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast) Mus Musculus (mouse)

TISSUE(S): Hepatocyte, Liver

SUBMITTER: Michael Lanz

LAB HEAD: Jan Skotheim

PROVIDER: PXD052786 | Pride | 2024-06-05

REPOSITORIES: Pride

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Genome dilution by cell growth drives starvation-like proteome remodeling in mammalian and yeast cells.

Lanz Michael C MC Zhang Shuyuan S Swaffer Matthew P MP Hernández Götz Luisa L McCarty Frank F Ziv Inbal I Jarosz Daniel F DF Elias Joshua E JE Skotheim Jan M JM

bioRxiv : the preprint server for biology 20231026

Cell size is tightly controlled in healthy tissues and single-celled organisms, but it remains unclear how size influences cell physiology. Increasing cell size was recently shown to remodel the proteomes of cultured human cells, demonstrating that large and small cells of the same type can be biochemically different. Here, we corroborate these results in mouse hepatocytes and extend our analysis using yeast. We find that size-dependent proteome changes are highly conserved and mostly independen ...[more]

PMID: 37905015

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