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Mild Hyperthermia-Induced Thermogenesis in the Endoplasmic Reticulum Defines Stress Response Mechanisms
Barbara Dukic1,2, Zsófia Ruppert1,3, Melinda E Tóth1
1Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary.
Cells
|July 12, 2024
Summary
Mild heat stress triggers the unfolded protein response (UPR) by causing endoplasmic reticulum (ER) thermogenesis in cells. This intracellular temperature increase, linked to SERCA pump uncoupling, dictates cellular stress responses.
Area of Science:
- Cell Biology
- Biophysics
- Molecular Biology
Background:
- Mild hyperthermia can induce the unfolded protein response (UPR) in mammalian cells.
- The UPR is a cellular stress response pathway crucial for maintaining protein homeostasis.
Purpose of the Study:
- To investigate the role of intracellular thermogenesis in mild heat-induced UPR.
- To explore the mechanism of ER temperature regulation during hyperthermic stress.
- To compare cellular responses to mild heat stress in different cell lines.
Main Methods:
- dSTORM super-resolution microscopy to observe IRE1 clustering.
- ER thermo yellow fluorescent probe for ER temperature measurement.
- Comparison of mouse embryonic fibroblast (MEF) and human osteosarcoma (U2OS) cell lines.
Main Results:
- Mild heat stress caused IRE1 clustering, a UPR marker, in U2OS cells.
- MEF cells exhibited significant intracellular thermogenesis in the ER (up to 40°C), linked to SERCA pump uncoupling.
- High ER temperatures in MEF cells triggered a pronounced cytosolic heat-shock response, absent in U2OS cells.
Conclusions:
- Intracellular thermogenesis in the ER is a key mechanism in the cellular response to mild hyperthermia.
- Cellular properties influence the occurrence of ER thermogenesis and subsequent stress responses.
- SERCA pump activity is implicated in regulating ER temperature during heat stress.
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