Mild Hyperthermia-Induced Thermogenesis in the Endoplasmic Reticulum Defines Stress Response Mechanisms

Autor: Barbara Dukic, Zsófia Ruppert, Melinda E. Tóth, Ákos Hunya, Ágnes Czibula, Péter Bíró, Ádám Tiszlavicz, Mária Péter, Gábor Balogh, Miklós Erdélyi, Gyula Timinszky, László Vígh, Imre Gombos, Zsolt Török
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cells, Vol 13, Iss 13, p 1141 (2024)
Druh dokumentu: article
ISSN: 13131141
2073-4409
DOI: 10.3390/cells13131141
Popis: Previous studies reported that a mild, non-protein-denaturing, fever-like temperature increase induced the unfolded protein response (UPR) in mammalian cells. Our dSTORM super-resolution microscopy experiments revealed that the master regulator of the UPR, the IRE1 (inositol-requiring enzyme 1) protein, is clustered as a result of UPR activation in a human osteosarcoma cell line (U2OS) upon mild heat stress. Using ER thermo yellow, a temperature-sensitive fluorescent probe targeted to the endoplasmic reticulum (ER), we detected significant intracellular thermogenesis in mouse embryonic fibroblast (MEF) cells. Temperatures reached at least 8 °C higher than the external environment (40 °C), resulting in exceptionally high ER temperatures similar to those previously described for mitochondria. Mild heat-induced thermogenesis in the ER of MEF cells was likely due to the uncoupling of the Ca2+/ATPase (SERCA) pump. The high ER temperatures initiated a pronounced cytosolic heat-shock response in MEF cells, which was significantly lower in U2OS cells in which both the ER thermogenesis and SERCA pump uncoupling were absent. Our results suggest that depending on intrinsic cellular properties, mild hyperthermia-induced intracellular thermogenesis defines the cellular response mechanism and determines the outcome of hyperthermic stress.
Databáze: Directory of Open Access Journals
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