{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:58Z","timestamp":1787027818437,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian Research Network","award":["SA-72\/2021"],"award-info":[{"award-number":["SA-72\/2021"]}]},{"name":"Hungarian Research Network","award":["OTKA ANN132280"],"award-info":[{"award-number":["OTKA ANN132280"]}]},{"name":"Hungarian Research Network","award":["OTKA K135759"],"award-info":[{"award-number":["OTKA K135759"]}]},{"name":"Hungarian Research Network","award":["OTKA K143248"],"award-info":[{"award-number":["OTKA K143248"]}]},{"name":"Hungarian Research Network","award":["OTKA FK135699"],"award-info":[{"award-number":["OTKA FK135699"]}]},{"name":"Hungarian Research Network","award":["2018-1.1.2-KFI-2018-00202"],"award-info":[{"award-number":["2018-1.1.2-KFI-2018-00202"]}]},{"name":"Hungarian Research Network","award":["TKP2021-NVA-19"],"award-info":[{"award-number":["TKP2021-NVA-19"]}]},{"name":"National Research, Development and Innovation Office","award":["SA-72\/2021"],"award-info":[{"award-number":["SA-72\/2021"]}]},{"name":"National Research, Development and Innovation Office","award":["OTKA ANN132280"],"award-info":[{"award-number":["OTKA ANN132280"]}]},{"name":"National Research, Development and Innovation Office","award":["OTKA K135759"],"award-info":[{"award-number":["OTKA K135759"]}]},{"name":"National Research, Development and Innovation Office","award":["OTKA K143248"],"award-info":[{"award-number":["OTKA K143248"]}]},{"name":"National Research, Development and Innovation Office","award":["OTKA FK135699"],"award-info":[{"award-number":["OTKA FK135699"]}]},{"name":"National Research, Development and Innovation Office","award":["2018-1.1.2-KFI-2018-00202"],"award-info":[{"award-number":["2018-1.1.2-KFI-2018-00202"]}]},{"name":"National Research, Development and Innovation Office","award":["TKP2021-NVA-19"],"award-info":[{"award-number":["TKP2021-NVA-19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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 \u00b0C higher than the external environment (40 \u00b0C), 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.<\/jats:p>","DOI":"10.3390\/cells13131141","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T08:45:34Z","timestamp":1719996334000},"page":"1141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mild Hyperthermia-Induced Thermogenesis in the Endoplasmic Reticulum Defines Stress Response Mechanisms"],"prefix":"10.3390","volume":"13","author":[{"given":"Barbara","family":"Dukic","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"},{"name":"Doctoral School of Environmental Sciences, Faculty of Science and Informatics, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8543-7198","authenticated-orcid":false,"given":"Zs\u00f3fia","family":"Ruppert","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"},{"name":"Doctoral School of Biology, Faculty of Science and Informatics, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda E.","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4547-9284","authenticated-orcid":false,"given":"\u00c1kos","family":"Hunya","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-2773","authenticated-orcid":false,"given":"\u00c1gnes","family":"Czibula","sequence":"additional","affiliation":[{"name":"Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"},{"name":"Department of Immunology, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8103-6248","authenticated-orcid":false,"given":"P\u00e9ter","family":"B\u00edr\u00f3","sequence":"additional","affiliation":[{"name":"Department of Optics and Quantum Electronics, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1d\u00e1m","family":"Tiszlavicz","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ria","family":"P\u00e9ter","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4565-6850","authenticated-orcid":false,"given":"G\u00e1bor","family":"Balogh","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"Erd\u00e9lyi","sequence":"additional","affiliation":[{"name":"Department of Optics and Quantum Electronics, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyula","family":"Timinszky","sequence":"additional","affiliation":[{"name":"Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7450-105X","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"V\u00edgh","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imre","family":"Gombos","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-3247","authenticated-orcid":false,"given":"Zsolt","family":"T\u00f6r\u00f6k","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/febs.14608","article-title":"Endoplasmic Reticulum Stress Signalling \u2013 from Basic Mechanisms to Clinical Applications","volume":"286","author":"Almanza","year":"2019","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/s41392-023-01570-w","article-title":"Endoplasmic Reticulum Stress: Molecular Mechanism and Therapeutic Targets - Signal Transduction and Targeted Therapy","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm2199","article-title":"Signal Integration in the Endoplasmic Reticulum Unfolded Protein Response","volume":"8","author":"Ron","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15643","DOI":"10.1038\/s41598-017-15821-8","article-title":"Mild Heat Induces a Distinct \u201cEustress\u201d Response in Chinese Hamster Ovary Cells but Does Not Induce Heat Shock Protein Synthesis","volume":"7","author":"Peksel","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tiszlavicz, \u00c1., Gombos, I., P\u00e9ter, M., Heged\u0171s, Z., Hunya, \u00c1., Dukic, B., Nagy, I., Peksel, B., Balogh, G., and Horv\u00e1th, I. (2022). Distinct Cellular Tools of Mild Hyperthermia-Induced Acquired Stress Tolerance in Chinese Hamster Ovary Cells. Biomedicines, 10.","DOI":"10.3390\/biomedicines10051172"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.bbamcr.2014.09.016","article-title":"Thermotolerance Induced at a Mild Temperature of 40\u00b0C Alleviates Heat Shock-Induced ER Stress and Apoptosis in HeLa Cells","volume":"1853","author":"Bettaieb","year":"2015","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Xu, X., Gupta, S., Hu, W., McGrath, B.C., and Cavener, D.R. (2011). Hyperthermia Induces the ER Stress Pathway. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023740"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Adams, C.J., Kopp, M.C., Larburu, N., Nowak, P.R., and Ali, M.M.U. (2019). Structure and Molecular Mechanism of ER Stress Signaling by the Unfolded Protein Response Signal Activator IRE1. Front. Mol. Biosci., 6.","DOI":"10.3389\/fmolb.2019.00011"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lindholm, D., Korhonen, L., Eriksson, O., and K\u00f5ks, S. (2017). Recent Insights into the Role of Unfolded Protein Response in ER Stress in Health and Disease. Front. Cell Dev. Biol., 5.","DOI":"10.3389\/fcell.2017.00048"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Radanovi\u0107, T., and Ernst, R. (2021). The Unfolded Protein Response as a Guardian of the Secretory Pathway. Cells, 10.","DOI":"10.20944\/preprints202110.0447.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ceb.2018.04.013","article-title":"Cellular Mechanisms of Physicochemical Membrane Homeostasis","volume":"53","author":"Ernst","year":"2018","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Fun, X.H., and Thibault, G. (2020). Lipid Bilayer Stress and Proteotoxic Stress-Induced Unfolded Protein Response Deploy Divergent Transcriptional and Non-Transcriptional Programmes. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1865.","DOI":"10.1016\/j.bbalip.2019.04.009"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.bcp.2018.02.022","article-title":"Lipid Bilayer Stress in Obesity-Linked Inflammatory and Metabolic Disorders","volume":"153","author":"Gianfrancesco","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.molcel.2017.06.012","article-title":"Activation of the Unfolded Protein Response by Lipid Bilayer Stress","volume":"67","author":"Halbleib","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.devcel.2018.04.023","article-title":"The UPR Activator ATF6 Responds to Proteotoxic and Lipotoxic Stress by Distinct Mechanisms","volume":"46","author":"Tam","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3390\/metabo11010052","article-title":"Beyond Proteostasis: Lipid Metabolism as a New Player in Er Homeostasis","volume":"11","author":"Xu","year":"2021","journal-title":"Metabolites"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00018-022-04523-8","article-title":"The Multiple Facets of Mitochondrial Regulations Controlling Cellular Thermogenesis","volume":"79","author":"Beignon","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chr\u00e9tien, D., B\u00e9nit, P., Ha, H.-H., Keipert, S., El-Khoury, R., Chang, Y.-T., Jastroch, M., Jacobs, H.T., Rustin, P., and Rak, M. (2018). Mitochondria Are Physiologically Maintained at Close to 50 \u00b0C. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2003992"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Terzioglu, M., Veeroja, K., Montonen, T., Ihalainen, T.O., Salminen, T.S., B\u00e9nit, P., Rustin, P., Chang, Y.-T., Nagai, T., and Jacobs, H.T. Mitochondrial Temperature Homeostasis Resists External Metabolic Stresses; elife, 2023; 12, RP89232.","DOI":"10.7554\/eLife.89232"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6701","DOI":"10.1038\/srep06701","article-title":"A Molecular Fluorescent Probe for Targeted Visualization of Temperature at the Endoplasmic Reticulum","volume":"4","author":"Arai","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Macherel, D., Haraux, F., Guillou, H., and Bourgeois, O. (2021). The Conundrum of Hot Mitochondria. Biochim. Biophys. Acta - Bioenerg., 1862.","DOI":"10.1016\/j.bbabio.2020.148348"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e74342","DOI":"10.7554\/eLife.74342","article-title":"Endoplasmic Reticulum Stress Activates Human IRE1\u03b1 through Reversible Assembly of Inactive Dimers into Small Oligomers","volume":"11","author":"Belyy","year":"2022","journal-title":"eLife"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1089\/adt.2018.862","article-title":"Improved IRE1 and PERK Pathway Sensors for Multiplex Endoplasmic Reticulum Stress Assay Reveal Stress Response to Nuclear Dyes Used for Image Segmentation","volume":"16","author":"Ylanko","year":"2018","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lebeau, P.F., Platko, K., Byun, J.H., and Austin, R.C. (2021). Calcium as a Reliable Marker for the Quantitative Assessment of Endoplasmic Reticulum Stress in Live Cells. J. Biol. Chem., 296.","DOI":"10.1016\/j.jbc.2021.100779"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"094012","DOI":"10.1088\/2040-8978\/15\/9\/094012","article-title":"Elements of Image Processing in Localization Microscopy","volume":"15","author":"Rees","year":"2013","journal-title":"J. Opt."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1073\/pnas.1915311117","article-title":"Quantitative Microscopy Reveals Dynamics and Fate of Clustered IRE1\u03b1","volume":"117","author":"Belyy","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00232-001-0171-5","article-title":"Ca2+-ATPases (SERCA): Energy Transduction and Heat Production in Transport ATPases","volume":"188","author":"Meis","year":"2002","journal-title":"J. Membr. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1083\/jcb.201003138","article-title":"Regulation of Basal Cellular Physiology by the Homeostatic Unfolded Protein Response","volume":"189","author":"Rutkowski","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8506","DOI":"10.1128\/MCB.22.24.8506-8513.2002","article-title":"Heat Shock Protein 90 Modulates the Unfolded Protein Response by Stabilizing IRE1alpha","volume":"22","author":"Marcu","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Somogyv\u00e1ri, M., Khatatneh, S., and S\u0151ti, C. (2022). Hsp90: From Cellular to Organismal Proteostasis. Cells, 11.","DOI":"10.3390\/cells11162479"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5729710","DOI":"10.1155\/2019\/5729710","article-title":"The Role of the ER-Induced UPR Pathway and the Efficacy of Its Inhibitors and Inducers in the Inhibition of Tumor Progression","volume":"2019","author":"Walczak","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/1567-1364.12125","article-title":"Management of the Endoplasmic Reticulum Stress by Activation of the Heat Shock Response in Yeast","volume":"14","author":"Hou","year":"2014","journal-title":"FEMS Yeast Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1034\/j.1600-0854.2002.31102.x","article-title":"Secretory Pathway Quality Control Operating in Golgi, Plasmalemmal, and Endosomal Systems","volume":"3","author":"Arvan","year":"2002","journal-title":"Traffic Cph. Den."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Alagar Boopathy, L.R., Jacob-Tomas, S., Alecki, C., and Vera, M. (2022). Mechanisms Tailoring the Expression of Heat Shock Proteins to Proteostasis Challenges. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.101796"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8637","DOI":"10.1038\/s41598-019-45020-6","article-title":"Membrane Phospholipid Alteration Causes Chronic ER Stress through Early Degradation of Homeostatic ER-Resident Proteins","volume":"9","author":"Shyu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101198","DOI":"10.1016\/j.plipres.2022.101198","article-title":"Endoplasmic Reticulum Stress and Lipids in Health and Diseases","volume":"89","author":"Celik","year":"2023","journal-title":"Prog. Lipid Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/1751-7915.13032","article-title":"Membrane Fluidification by Ethanol Stress Activates Unfolded Protein Response in Yeasts","volume":"11","author":"Querol","year":"2018","journal-title":"Microb. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.tibs.2023.08.004","article-title":"Membrane Homeostasis beyond Fluidity: Control of Membrane Compressibility","volume":"48","author":"Renne","year":"2023","journal-title":"Trends Biochem. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1016\/j.bbamem.2011.07.022","article-title":"Fluid Phase Lipid Areas and Bilayer Thicknesses of Commonly Used Phosphatidylcholines as a Function of Temperature","volume":"1808","author":"Nieh","year":"2011","journal-title":"Biochim. Biophys. Acta BBA - Biomembr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1529\/biophysj.107.115691","article-title":"Temperature Dependence of Structure, Bending Rigidity, and Bilayer Interactions of Dioleoylphosphatidylcholine Bilayers","volume":"94","author":"Pan","year":"2008","journal-title":"Biophys. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1091\/mbc.e17-03-0144","article-title":"Generic Membrane-Spanning Features Endow IRE1\u03b1 with Responsiveness to Membrane Aberrancy","volume":"28","author":"Kono","year":"2017","journal-title":"Mol. Biol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.cell.2012.09.010","article-title":"Mechanism of Fatty-Acid-Dependent UCP1 Uncoupling in Brown Fat Mitochondria","volume":"151","author":"Fedorenko","year":"2012","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1038\/nm.2897","article-title":"Sarcolipin Is a Newly Identified Regulator of Muscle-Based Thermogenesis in Mammals","volume":"18","author":"Bal","year":"2012","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bal, N.C., and Periasamy, M. (2020). Uncoupling of Sarcoendoplasmic Reticulum Calcium ATPase Pump Activity by Sarcolipin as the Basis for Muscle Non-Shivering Thermogenesis. Philos. Trans. R. Soc. B Biol. Sci., 375.","DOI":"10.1098\/rstb.2019.0135"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1146\/annurev.ph.56.030194.002535","article-title":"Thermogenesis in Muscle","volume":"56","author":"Block","year":"1994","journal-title":"Annu. Rev. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev.biophys.36.040306.132643","article-title":"Bilayer Thickness and Membrane Protein Function: An Energetic Perspective","volume":"36","author":"Andersen","year":"2007","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1021\/bi00510a034","article-title":"Fluorescence Quenching in Model Membranes. 3. Relationship between Calcium Adenosinetriphosphatase Enzyme Activity and the Affinity of the Protein for Phosphatidylcholines with Different Acyl Chain Characteristicst","volume":"20","author":"Caffrey","year":"1981","journal-title":"Biochemistry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.bpc.2005.09.007","article-title":"Influence of N-Dodecyl-N,N-Dimethylamine N-Oxide on the Activity of Sarcoplasmic Reticulum Ca2+-Transporting ATPase Reconstituted into Diacylphosphatidylcholine Vesicles: Effects of Bilayer Physical Parameters","volume":"119","author":"Teixeira","year":"2006","journal-title":"Biophys. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1080\/02656730500307298","article-title":"How Do Cells Respond to Their Thermal Environment?","volume":"21","author":"Lepock","year":"2005","journal-title":"Int. J. Hyperthermia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/s41598-017-00291-9","article-title":"Optical Visualisation of Thermogenesis in Stimulated Single-Cell Brown Adipocytes","volume":"7","author":"Kriszt","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1038\/nm.4429","article-title":"UCP1-Independent Signaling Involving SERCA2b-Mediated Calcium Cycling Regulates Beige Fat Thermogenesis and Systemic Glucose Homeostasis","volume":"23","author":"Ikeda","year":"2017","journal-title":"Nat. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1016\/j.bbamem.2013.12.015","article-title":"Plasma Membranes as Heat Stress Sensors: From Lipid-Controlled Molecular Switches to Therapeutic Applications","volume":"1838","author":"Crul","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/B978-0-444-64074-1.00035-5","article-title":"Stress-Induced Hyperthermia and Hypothermia","volume":"157","author":"Oka","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/emboj.2008.42","article-title":"Heat Shock Response Relieves ER Stress","volume":"27","author":"Liu","year":"2008","journal-title":"EMBO J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1016\/j.febslet.2013.05.016","article-title":"Key Role of Lipids in Heat Stress Management","volume":"587","author":"Balogh","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0968-0004(98)01279-1","article-title":"Does the Membrane\u2019s Physical State Control the Expression of Heat Shock and Other Genes?","volume":"23","author":"Vigh","year":"1998","journal-title":"Trends Biochem. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/j.bbamem.2008.02.012","article-title":"Membrane-Associated Stress Proteins: More than Simply Chaperones","volume":"1778","author":"Multhoff","year":"2008","journal-title":"Biochim. Biophys. Acta BBA-Biomembr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nrneurol.2017.99","article-title":"ER Stress and the Unfolded Protein Response in Neurodegeneration","volume":"13","author":"Hetz","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.molmed.2011.07.010","article-title":"Endoplasmic Reticulum Stress, Obesity and Diabetes","volume":"18","author":"Cnop","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.bbrc.2017.01.154","article-title":"Saturation of SERCA\u2019s Lipid Annulus May Protect against Its Thermal Inactivation","volume":"484","author":"Fajardo","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e72861","DOI":"10.7554\/eLife.72861","article-title":"Alternate Patterns of Temperature Variation Bring about Very Different Disease Outcomes at Different Mean Temperatures","volume":"11","author":"Kunze","year":"2022","journal-title":"eLife"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/13\/1141\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:09:41Z","timestamp":1760108981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/13\/1141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,3]]},"references-count":61,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["cells13131141"],"URL":"https:\/\/doi.org\/10.3390\/cells13131141","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.05.24.595680","asserted-by":"object"}]},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,3]]}}}