The Heat Shock Response in Yeast Maintains Protein Homeostasis by Chaperoning and Replenishing Proteins

Summary: Life is resilient because living systems are able to respond to elevated temperatures with an ancient gene expression program called the heat shock response (HSR). In yeast, the transcription of hundreds of genes is upregulated at stress temperatures. Besides stress protection conferred by...

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Main Authors: Moritz Mühlhofer, Evi Berchtold, Chris G. Stratil, Gergely Csaba, Elena Kunold, Nina C. Bach, Stephan A. Sieber, Martin Haslbeck, Ralf Zimmer, Johannes Buchner
Format: Article
Language:English
Published: Elsevier 2019-12-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719316328
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author Moritz Mühlhofer
Evi Berchtold
Chris G. Stratil
Gergely Csaba
Elena Kunold
Nina C. Bach
Stephan A. Sieber
Martin Haslbeck
Ralf Zimmer
Johannes Buchner
author_facet Moritz Mühlhofer
Evi Berchtold
Chris G. Stratil
Gergely Csaba
Elena Kunold
Nina C. Bach
Stephan A. Sieber
Martin Haslbeck
Ralf Zimmer
Johannes Buchner
author_sort Moritz Mühlhofer
collection DOAJ
description Summary: Life is resilient because living systems are able to respond to elevated temperatures with an ancient gene expression program called the heat shock response (HSR). In yeast, the transcription of hundreds of genes is upregulated at stress temperatures. Besides stress protection conferred by chaperones, the function of the majority of the upregulated genes under stress has remained enigmatic. We show that those genes are required to directly counterbalance increased protein turnover at stress temperatures and to maintain the metabolism. This anaplerotic reaction together with molecular chaperones allows yeast to efficiently buffer proteotoxic stress. When the capacity of this system is exhausted at extreme temperatures, aggregation processes stop translation and growth pauses. The emerging concept is that the HSR is modular with distinct programs dependent on the severity of the stress. : Mühlhofer et al. show that under mild and severe heat stress, proteins lost due to increased aggregation and degradation are replenished by increased protein synthesis to ensure a constant pool of proteins, together with the molecular chaperones. The heat shock response is activated in modules by transcriptional regulation. Keywords: heat shock response, protein aggregation, chaperones, transcriptome, translatome, proteome, S. cerevisiae, ribosome profiling, mass spectrometry
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spelling doaj.art-4d1484a5a9214374857af164b3a56f322022-12-21T19:38:19ZengElsevierCell Reports2211-12472019-12-01291345934607.e8The Heat Shock Response in Yeast Maintains Protein Homeostasis by Chaperoning and Replenishing ProteinsMoritz Mühlhofer0Evi Berchtold1Chris G. Stratil2Gergely Csaba3Elena Kunold4Nina C. Bach5Stephan A. Sieber6Martin Haslbeck7Ralf Zimmer8Johannes Buchner9Center for Integrated Protein Science at the Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, GermanyInstitute of Bioinformatics, Department of Informatics, Ludwig-Maximilians-Universität München, Amalienstrasse 17, 80333 Munich, GermanyCenter for Integrated Protein Science at the Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, GermanyInstitute of Bioinformatics, Department of Informatics, Ludwig-Maximilians-Universität München, Amalienstrasse 17, 80333 Munich, GermanyCenter for Integrated Protein Science at the Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, GermanyCenter for Integrated Protein Science at the Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, GermanyCenter for Integrated Protein Science at the Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, GermanyCenter for Integrated Protein Science at the Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, GermanyInstitute of Bioinformatics, Department of Informatics, Ludwig-Maximilians-Universität München, Amalienstrasse 17, 80333 Munich, GermanyCenter for Integrated Protein Science at the Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany; Corresponding authorSummary: Life is resilient because living systems are able to respond to elevated temperatures with an ancient gene expression program called the heat shock response (HSR). In yeast, the transcription of hundreds of genes is upregulated at stress temperatures. Besides stress protection conferred by chaperones, the function of the majority of the upregulated genes under stress has remained enigmatic. We show that those genes are required to directly counterbalance increased protein turnover at stress temperatures and to maintain the metabolism. This anaplerotic reaction together with molecular chaperones allows yeast to efficiently buffer proteotoxic stress. When the capacity of this system is exhausted at extreme temperatures, aggregation processes stop translation and growth pauses. The emerging concept is that the HSR is modular with distinct programs dependent on the severity of the stress. : Mühlhofer et al. show that under mild and severe heat stress, proteins lost due to increased aggregation and degradation are replenished by increased protein synthesis to ensure a constant pool of proteins, together with the molecular chaperones. The heat shock response is activated in modules by transcriptional regulation. Keywords: heat shock response, protein aggregation, chaperones, transcriptome, translatome, proteome, S. cerevisiae, ribosome profiling, mass spectrometryhttp://www.sciencedirect.com/science/article/pii/S2211124719316328
spellingShingle Moritz Mühlhofer
Evi Berchtold
Chris G. Stratil
Gergely Csaba
Elena Kunold
Nina C. Bach
Stephan A. Sieber
Martin Haslbeck
Ralf Zimmer
Johannes Buchner
The Heat Shock Response in Yeast Maintains Protein Homeostasis by Chaperoning and Replenishing Proteins
Cell Reports
title The Heat Shock Response in Yeast Maintains Protein Homeostasis by Chaperoning and Replenishing Proteins
title_full The Heat Shock Response in Yeast Maintains Protein Homeostasis by Chaperoning and Replenishing Proteins
title_fullStr The Heat Shock Response in Yeast Maintains Protein Homeostasis by Chaperoning and Replenishing Proteins
title_full_unstemmed The Heat Shock Response in Yeast Maintains Protein Homeostasis by Chaperoning and Replenishing Proteins
title_short The Heat Shock Response in Yeast Maintains Protein Homeostasis by Chaperoning and Replenishing Proteins
title_sort heat shock response in yeast maintains protein homeostasis by chaperoning and replenishing proteins
url http://www.sciencedirect.com/science/article/pii/S2211124719316328
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