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PreprintCC BY-NC-NDbioRxiv

PKA-regulated carbohydrate production protects cells by altering cytoplasmic biophysical properties

  1. 1Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland

Abstract

Proliferating cells maintain their cytoplasmic density within a narrow range but deviate when entering quiescence or experiencing stress, suggesting active regulation. The mechanisms driving these density adjustments and their impact on cellular function remain unclear. Here, we demonstrate that the conserved cAMP-activated protein kinase A (PKA) is a key regulator of cytoplasmic properties. Inactivation of PKA leads to a drastic increase in cytoplasmic dry mass density and reduced diffusion that depends on the environmental stress response (ESR) transcription factors Msn2/4. This change is mediated by the accumulation of glycogen and trehalose, which have opposing effects on intracellular diffusion. Importantly, the accumulation of these carbohydrates confers stress resistance in distinct ways and independently of their roles as energy sources. Our findings highlight the importance of the biophysical properties of the cytoplasm in stress resistance and the role of glycogen and trehalose in regulating these properties.

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BibTeX
@misc{kunzi2026pkaregulated,
  title = {{PKA-regulated carbohydrate production protects cells by altering cytoplasmic biophysical properties}},
  author = {M. Kunzi and L. Kronig and M. Bonassera and P. A. Gomez-Garcia and M. Peter and K. Weis and G. E. Neurohr},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.29.747980},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.29.747980v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - PKA-regulated carbohydrate production protects cells by altering cytoplasmic biophysical properties
AU  - M. Kunzi
AU  - L. Kronig
AU  - M. Bonassera
AU  - P. A. Gomez-Garcia
AU  - M. Peter
AU  - K. Weis
AU  - G. E. Neurohr
PY  - 2026
DA  - 2026/08/29
PB  - bioRxiv
DO  - 10.64898/2026.08.29.747980
UR  - https://www.biorxiv.org/content/10.64898/2026.08.29.747980v1
AB  - Proliferating cells maintain their cytoplasmic density within a narrow range but deviate when entering quiescence or experiencing stress, suggesting active regulation. The mechanisms driving these density adjustments and their impact on cellular function remain unclear. Here, we demonstrate that the conserved cAMP-activated protein kinase A (PKA) is a key regulator of cytoplasmic properties. Inactivation of PKA leads to a drastic increase in cytoplasmic dry mass density and reduced diffusion that depends on the environmental stress response (ESR) transcription factors Msn2/4. This change is mediated by the accumulation of glycogen and trehalose, which have opposing effects on intracellular diffusion. Importantly, the accumulation of these carbohydrates confers stress resistance in distinct ways and independently of their roles as energy sources. Our findings highlight the importance of the biophysical properties of the cytoplasm in stress resistance and the role of glycogen and trehalose in regulating these properties.
ER  -