Fine-Tuning of the Endoplasmic Reticulum Stress Response Mechanism Plays a Key Role in Cellular Survival-A Mathematical Study.

Proper functioning of the endoplasmic reticulum (ER) plays a key role in maintaining the internal homeostasis of the cell. A common feature of many common diseases (such as diabetes and inflammatory bowel diseases) is the induction of ER stress in cells. While some ER stress is beneficial for cellular survival, high levels of stress can lead to cell death. For this reason, many studies are focused on understanding the exact mechanism of the ER stress response. There are a variety of well-established stressors on the market that can be used to induce ER stress under laboratory conditions (i.e., thapsigargin and tunicamycin). However, new scientific results suggest that these ER stressors act very differently on the stress response mechanism and, therefore, cannot always be used reliably. By using various mathematical methods, our systems biology approach presented here seeks to answer how the well-known ER stressors affect the dynamic characteristic of the control network, specifically highlighting how we can delay the negative impact of ER stress. Furthermore, using mathematical models, we make suggestions on which ER stressors may be useful in which therapeutic treatment.