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Chronic starvation induces noncanonical pro-death stress granules

Lucas C Reineke1,2, Shebna A Cheema3,4, Julien Dubrulle5

  • 1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA lcreinek@bcm.edu neilson@bcm.edu.

Journal of Cell Science
|September 7, 2018
PubMed

Insights

Chronic nutrient starvation forms unique stress granules (SGs) lacking ribosomes that promote cell death, differing from acute stress responses. These starvation-induced SGs (stSGs) reveal new insights into cellular stress adaptation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Stress granules (SGs) are cytoplasmic foci that assemble during cellular stress, inhibiting protein synthesis.
  • SGs are classically composed of translation factors, ribosomes, RNA-binding proteins, and mRNAs, regulating translation and promoting survival.
  • Existing research often uses acute stress models, potentially not reflecting chronic stress conditions in diseases.

Purpose of the Study:

  • To investigate the formation and function of SGs under prolonged nutrient starvation, a model for chronic stress.
  • To characterize the composition and behavior of SGs formed during chronic nutrient deprivation.
  • To compare SGs formed under chronic stress with those formed under acute stress conditions.

Main Methods:

  • Utilized prolonged nutrient starvation in human cell lines and mouse embryonic fibroblasts.
  • Analyzed the composition of stress granules, specifically looking for the presence of 40S ribosomes.
  • Investigated the dynamic exchange of components within stress granules and their effect on cell viability.

Main Results:

  • Discovered novel stress granules, termed starvation-induced SGs (stSGs), under prolonged nutrient starvation.
  • stSGs were found to lack 40S ribosomes, distinguishing them from classically defined SGs.
  • These stSGs exhibited limited component exchange and were associated with promoting cell death, not survival.

Conclusions:

  • Stress granule assembly and function differ significantly between acute and chronic stress conditions.
  • Starvation-induced SGs (stSGs) represent a distinct subset of SGs with unique properties and implications for cell fate.
  • These findings challenge the classical view of SGs and highlight their complex roles in cellular responses to prolonged stress.
Keywords:
Cell deathG3BP1StarvationStress granuleTranslationeIF2α

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