Nutrient Signaling, Stress Response, and Inter-organelle Communication Are Non-canonical Determinants of Cell Fate

N. Ezgi Wood, Piya Kositangool, Hanaa Hariri, Ashley J. Marchand, W. Mike Henne

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Isogenic cells manifest distinct cellular fates for a single stress; however, the nongenetic mechanisms driving such fates remain poorly understood. Here, we implement a robust multi-channel live-cell imaging approach to uncover noncanonical factors governing cell fate. We show that in response to acute glucose removal (AGR), budding yeast undergoes distinct fates, becoming either quiescent or senescent. Senescent cells fail to resume mitotic cycles following glucose replenishment but remain responsive to nutrient stimuli. Whereas quiescent cells manifest starvation-induced adaptation, senescent cells display perturbed endomembrane trafficking and defective nucleus-vacuole junction (NVJ) expansion. Surprisingly, senescence occurs even in the absence of lipid droplets. Importantly, we identify the nutrient-sensing kinase Rim15 as a key biomarker predicting cell fates before AGR stress. We propose that isogenic yeast challenged with acute nutrient shortage contains determinants influencing post-stress fate and demonstrate that specific nutrient signaling, stress response, trafficking, and inter-organelle biomarkers are early indicators for long-term fate outcomes.

Original languageEnglish (US)
Article number108446
JournalCell Reports
Volume33
Issue number9
DOIs
StatePublished - Dec 1 2020

Keywords

  • Bayesian analysis
  • LD
  • NVJ
  • cell cycle
  • cellular decision making
  • lipid droplet
  • nucleus-vacuole junction
  • quantitative imaging
  • quiescence
  • senescence
  • statistical evidence

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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