Hsf1 and the molecular chaperone Hsp90 support a ‘rewiring stress response’ leading to an adaptive cell size increase in chronic stress
Cells are exposed to a wide variety of internal and external stresses. Although many studies have focused on cellular responses to acute and severe stresses, little is known about how cellular systems adapt to sublethal chronic stresses. Using mammalian cells in culture, we discovered that they adap...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2023-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/88658 |
| _version_ | 1797401360797270016 |
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| author | Samarpan Maiti Kaushik Bhattacharya Diana Wider Dina Hany Olesya Panasenko Lilia Bernasconi Nicolas Hulo Didier Picard |
| author_facet | Samarpan Maiti Kaushik Bhattacharya Diana Wider Dina Hany Olesya Panasenko Lilia Bernasconi Nicolas Hulo Didier Picard |
| author_sort | Samarpan Maiti |
| collection | DOAJ |
| description | Cells are exposed to a wide variety of internal and external stresses. Although many studies have focused on cellular responses to acute and severe stresses, little is known about how cellular systems adapt to sublethal chronic stresses. Using mammalian cells in culture, we discovered that they adapt to chronic mild stresses of up to two weeks, notably proteotoxic stresses such as heat, by increasing their size and translation, thereby scaling the amount of total protein. These adaptations render them more resilient to persistent and subsequent stresses. We demonstrate that Hsf1, well known for its role in acute stress responses, is required for the cell size increase, and that the molecular chaperone Hsp90 is essential for coupling the cell size increase to augmented translation. We term this translational reprogramming the ‘rewiring stress response’, and propose that this protective process of chronic stress adaptation contributes to the increase in size as cells get older, and that its failure promotes aging. |
| first_indexed | 2024-03-09T02:08:56Z |
| format | Article |
| id | doaj.art-8dccfe64e7dd4eff8c8191177c079f57 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-09T02:08:56Z |
| publishDate | 2023-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8dccfe64e7dd4eff8c8191177c079f572023-12-07T15:21:17ZengeLife Sciences Publications LtdeLife2050-084X2023-12-011210.7554/eLife.88658Hsf1 and the molecular chaperone Hsp90 support a ‘rewiring stress response’ leading to an adaptive cell size increase in chronic stressSamarpan Maiti0https://orcid.org/0000-0001-9090-2398Kaushik Bhattacharya1Diana Wider2Dina Hany3Olesya Panasenko4Lilia Bernasconi5Nicolas Hulo6https://orcid.org/0000-0003-2640-636XDidier Picard7https://orcid.org/0000-0001-8816-9668Département de Biologie Moléculaire et Cellulaire, Université de Genève, Genève, SwitzerlandDépartement de Biologie Moléculaire et Cellulaire, Université de Genève, Genève, SwitzerlandDépartement de Biologie Moléculaire et Cellulaire, Université de Genève, Genève, SwitzerlandDépartement de Biologie Moléculaire et Cellulaire, Université de Genève, Genève, Switzerland; On leave from: Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, EgyptBioCode: RNA to Proteins Core Facility, Département de Microbiologie et Médecine Moléculaire, Faculté de Médecine, Université de Genève, Genève, SwitzerlandDépartement de Biologie Moléculaire et Cellulaire, Université de Genève, Genève, SwitzerlandInstitute of Genetics and Genomics of Geneva, Université de Genève, Genève, SwitzerlandDépartement de Biologie Moléculaire et Cellulaire, Université de Genève, Genève, SwitzerlandCells are exposed to a wide variety of internal and external stresses. Although many studies have focused on cellular responses to acute and severe stresses, little is known about how cellular systems adapt to sublethal chronic stresses. Using mammalian cells in culture, we discovered that they adapt to chronic mild stresses of up to two weeks, notably proteotoxic stresses such as heat, by increasing their size and translation, thereby scaling the amount of total protein. These adaptations render them more resilient to persistent and subsequent stresses. We demonstrate that Hsf1, well known for its role in acute stress responses, is required for the cell size increase, and that the molecular chaperone Hsp90 is essential for coupling the cell size increase to augmented translation. We term this translational reprogramming the ‘rewiring stress response’, and propose that this protective process of chronic stress adaptation contributes to the increase in size as cells get older, and that its failure promotes aging.https://elifesciences.org/articles/88658proteostasistranslationagingcytoplasmic densitystress adaptationsenescence |
| spellingShingle | Samarpan Maiti Kaushik Bhattacharya Diana Wider Dina Hany Olesya Panasenko Lilia Bernasconi Nicolas Hulo Didier Picard Hsf1 and the molecular chaperone Hsp90 support a ‘rewiring stress response’ leading to an adaptive cell size increase in chronic stress eLife proteostasis translation aging cytoplasmic density stress adaptation senescence |
| title | Hsf1 and the molecular chaperone Hsp90 support a ‘rewiring stress response’ leading to an adaptive cell size increase in chronic stress |
| title_full | Hsf1 and the molecular chaperone Hsp90 support a ‘rewiring stress response’ leading to an adaptive cell size increase in chronic stress |
| title_fullStr | Hsf1 and the molecular chaperone Hsp90 support a ‘rewiring stress response’ leading to an adaptive cell size increase in chronic stress |
| title_full_unstemmed | Hsf1 and the molecular chaperone Hsp90 support a ‘rewiring stress response’ leading to an adaptive cell size increase in chronic stress |
| title_short | Hsf1 and the molecular chaperone Hsp90 support a ‘rewiring stress response’ leading to an adaptive cell size increase in chronic stress |
| title_sort | hsf1 and the molecular chaperone hsp90 support a rewiring stress response leading to an adaptive cell size increase in chronic stress |
| topic | proteostasis translation aging cytoplasmic density stress adaptation senescence |
| url | https://elifesciences.org/articles/88658 |
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