Multiple system-level feedback loops control life-and-death decisions in endoplasmic reticulum stress

Orsolya Kapuy, Margita Márton, Gábor Bánhegyi, P. K. Vinod

Research output: Contribution to journalArticle

Abstract

Scientific results have revealed that autophagy is able to promote cell survival in response to endoplasmic reticulum (ER) stress, while drastic events result in apoptotic cell death. Here, we analyse the important crosstalk of life-and-death decisions from a systems biological perspective by studying the regulatory modules of the unfolded protein response (UPR). While a double-negative loop between autophagy and apoptosis inducers is crucial for the switch-like characteristic of the stress response mechanism, a positive feedback loop between ER stress sensors is also essential. Corresponding to experimental data, here, we show the dynamical significance of Gadd34-CHOP connections inside the PERK branch of the UPR. The multiple system-level feedback loops seem to be crucial for managing a robust life-and-death decision depending on the level and durability of cellular stress.

Original languageEnglish
Pages (from-to)1112-1123
Number of pages12
JournalFEBS letters
Volume594
Issue number6
DOIs
Publication statusPublished - Mar 1 2020

Keywords

  • apoptosis
  • autophagy
  • endoplasmic reticulum stress
  • feedback loops
  • systems biology

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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