Cellular Stress: Modulator of Regulated Cell Death

Prem Prasad Lamichhane, Parimal Samir

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations


Cellular stress response activates a complex program of an adaptive response called integrated stress response (ISR) that can allow a cell to survive in the presence of stressors. ISR reprograms gene expression to increase the transcription and translation of stress response genes while repressing the translation of most proteins to reduce the metabolic burden. In some cases, ISR activation can lead to the assembly of a cytoplasmic membraneless compartment called stress granules (SGs). ISR and SGs can inhibit apoptosis, pyroptosis, and necroptosis, suggesting that they guard against uncontrolled regulated cell death (RCD) to promote organismal homeostasis. However, ISR and SGs also allow cancer cells to survive in stressful environments, including hypoxia and during chemotherapy. Therefore, there is a great need to understand the molecular mechanism of the crosstalk between ISR and RCD. This is an active area of research and is expected to be relevant to a range of human diseases. In this review, we provided an overview of the interplay between different cellular stress responses and RCD pathways and their modulation in health and disease.

Original languageEnglish (US)
Article number1172
Issue number9
StatePublished - Sep 2023
Externally publishedYes


  • GCN2
  • HRI
  • PERK
  • PKR
  • apoptosis
  • integrated stress response
  • necroptosis
  • programmed cell death
  • pyroptosis
  • stress granules

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences


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