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Ribotoxic Stress Response: Coordinating Pyroptosis and Apoptosis

Jie Sun1,2, Yiyun Zhang3, Lisha Yan3

  • 1Department of Pathogenic Biology, College of Basic Medical Sciences, Jilin Medical University, Jilin City, People's Republic of China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 21, 2026
PubMed

Insights

The ribotoxic stress response (RSR) links ribosome stalling to cell death pathways like apoptosis and pyroptosis. Understanding RSR

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Immunology

Background:

  • Ribotoxic stress response (RSR) is a translation-dependent stress pathway triggered by ribosome stalling.
  • MAP3K/ZAKα kinase initiates RSR, influencing metabolism, immune signaling, and cell fate.
  • RSR is increasingly recognized for its role in coordinating apoptosis and pyroptosis.

Purpose of the Study:

  • To summarize current knowledge on RSR's molecular mechanisms.
  • To elucidate RSR's interface with apoptotic and pyroptotic pathways.
  • To discuss RSR's roles in cellular homeostasis and disease.

Main Methods:

  • Literature review and synthesis of existing research.
  • Analysis of molecular signaling pathways.
  • Discussion of RSR's implications in disease.

Main Results:

  • RSR acts as a crucial link between ribosome stress and programmed cell death.
  • RSR coordinates signaling crosstalk between apoptosis and pyroptosis.
  • Dysregulation of RSR is implicated in inflammatory disorders, immune dysfunction, and cancer.

Conclusions:

  • RSR plays a significant role in regulating cell death outcomes.
  • Targeting RSR could offer therapeutic strategies for diseases involving inflammation and cell death.
  • Further clarification of RSR's mechanisms is needed for therapeutic development.
Keywords:
ZAKαapoptosispyroptosisribotoxic stress responsetherapeutic target

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