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Updated: May 11, 2026
10:36
Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Endoplasmic reticulum stress: cell life and death decisions
Chunyan Xu1, Beatrice Bailly-Maitre, John C Reed
1The Burnham Institute for Medical Research, La Jolla, California 92037, USA.
The Journal of Clinical Investigation
|October 4, 2005
Summary
Cellular stress responses, like the unfolded protein response, aim to repair endoplasmic reticulum (ER) damage. However, prolonged ER dysfunction can trigger cell death, with mechanisms still under investigation for various diseases.
Area of Science:
- Cellular Biology
- Molecular Mechanisms of Disease
- Stress Response Pathways
Background:
- Endoplasmic reticulum (ER) dysfunction triggers the unfolded protein response (UPR), an evolutionarily conserved cellular stress mechanism.
- The UPR initially attempts to restore ER homeostasis but can lead to cell death under severe or prolonged stress.
- The precise molecular mechanisms linking ER stress to cell death remain incompletely understood.
Purpose of the Study:
- To elucidate the enigmatic mechanisms by which ER stress induces cell death.
- To identify the dominant death effectors in specific cellular contexts of ER dysfunction.
- To clarify the role of ER-initiated cell death in various pathological conditions.
Main Methods:
- Investigation of cellular responses to ER stress.
- Analysis of molecular pathways involved in ER-initiated cell death.
- Comparative studies across different disease models exhibiting ER dysfunction.
Main Results:
- Multiple potential participants in ER-initiated cell death have been identified.
- Significant variability exists in the dominant death effectors depending on the cellular context.
- ER stress-induced cell death pathways are implicated in diseases such as neurodegeneration and diabetes.
Conclusions:
- While the UPR is initially protective, sustained ER stress is a potent trigger for cell death.
- Understanding the specific ER-to-death signaling pathways is crucial for therapeutic development.
- ER-initiated cell death plays a critical role in the pathogenesis of diverse human diseases.
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