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Cell death induced by endoplasmic reticulum stress
Raffaella Iurlaro1, Cristina Muñoz-Pinedo1
1Cell Death Regulation Group, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain.
The FEBS Journal
|November 21, 2015
Summary
Cellular stress triggers the unfolded protein response (UPR) to restore balance. While aiming for homeostasis, this endoplasmic reticulum stress pathway can lead to cell death, impacting various diseases.
Area of Science:
- Cell Biology
- Molecular Biology
- Pathology
Background:
- The endoplasmic reticulum (ER) is vital for protein synthesis and folding.
- Cellular stress conditions like hypoxia and infection induce ER stress.
- ER stress challenges protein folding capacity, necessitating cellular responses.
Purpose of the Study:
- To elucidate the cellular mechanisms underlying the unfolded protein response (UPR).
- To explore the signaling pathways activated by ER stress.
- To understand the role of ER stress in various disease pathologies.
Main Methods:
- Analysis of key UPR sensors (PERK, IRE1, ATF6).
- Investigation of downstream signaling nodes (JNK, XBP1, ATF4, CHOP).
- Examination of cell death pathways (necroptosis, apoptosis, caspase-8 activation).
Main Results:
- UPR activation involves specific sensors and transcription factors.
- ER stress can trigger both homeostatic mechanisms and cell death pathways.
- The UPR intersects with the integrated stress response, affecting protein synthesis.
Conclusions:
- ER stress is implicated in neurodegeneration, stroke, cancer, metabolic diseases, and inflammation.
- Understanding ER stress mechanisms is crucial for developing therapeutic strategies.
- The UPR's dual role in homeostasis and cell death highlights its complex involvement in disease.
Keywords:
Bcl-2 family proteinsapoptosisautophagycaspase-8cell deathdeath receptorsendoplasmic reticulum stressiDISCmitochondrial pathwaynecrosisMore Related Videos
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