How Cells Adapt to Stress in the Endoplasmic Reticulum
Author Information
Author(s): Rutkowski D. Thomas, Arnold Stacey M, Miller Corey N, Wu Jun, Li Jack, Gunnison Kathryn M, Mori Kazutoshi, Sadighi Akha Amir A., Raden David, Kaufman Randal J
Primary Institution: Howard Hughes Medical Institute, University of Michigan Medical Center
Hypothesis
How do cells selectively utilize the adaptive program of the unfolded protein response (UPR) during ER stress?
Conclusion
Cells can adapt to chronic, mild ER stress without undergoing apoptosis due to the short-lived expression of pro-apoptotic proteins.
Supporting Evidence
- Cells under mild ER stress activate survival pathways while suppressing pro-apoptotic signals.
- Pro-apoptotic proteins like CHOP are short-lived, allowing cells to adapt.
- Adapted cells show persistent expression of survival proteins like BiP.
- Uggt1-deficient cells exhibit similar adaptive responses to pharmacological stress.
Takeaway
When cells are stressed, they can either survive or die. This study shows that under mild stress, cells can survive by keeping the proteins that help them live while letting go of the ones that cause them to die.
Methodology
The study used mouse embryonic fibroblasts (MEFs) to investigate the effects of mild ER stress induced by thapsigargin and tunicamycin on cell survival and protein expression.
Limitations
The study primarily focuses on a specific cell type and may not fully represent responses in other cell types or in vivo conditions.
Digital Object Identifier (DOI)
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