Nuclear Hsp104 safeguards the dormant translation machinery during quiescence
Abstract The resilience of cellular proteostasis declines with age, which drives protein aggregation and compromises viability. The nucleus has emerged as a key quality control compartment that handles misfolded proteins produced by the cytosolic protein biosynthesis system. Here, we find that age-a...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44538-8 |
| _version_ | 1827388329540190208 |
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| author | Verena Kohler Andreas Kohler Lisa Larsson Berglund Xinxin Hao Sarah Gersing Axel Imhof Thomas Nyström Johanna L. Höög Martin Ott Claes Andréasson Sabrina Büttner |
| author_facet | Verena Kohler Andreas Kohler Lisa Larsson Berglund Xinxin Hao Sarah Gersing Axel Imhof Thomas Nyström Johanna L. Höög Martin Ott Claes Andréasson Sabrina Büttner |
| author_sort | Verena Kohler |
| collection | DOAJ |
| description | Abstract The resilience of cellular proteostasis declines with age, which drives protein aggregation and compromises viability. The nucleus has emerged as a key quality control compartment that handles misfolded proteins produced by the cytosolic protein biosynthesis system. Here, we find that age-associated metabolic cues target the yeast protein disaggregase Hsp104 to the nucleus to maintain a functional nuclear proteome during quiescence. The switch to respiratory metabolism and the accompanying decrease in translation rates direct cytosolic Hsp104 to the nucleus to interact with latent translation initiation factor eIF2 and to suppress protein aggregation. Hindering Hsp104 from entering the nucleus in quiescent cells results in delayed re-entry into the cell cycle due to compromised resumption of protein synthesis. In sum, we report that cytosolic-nuclear partitioning of the Hsp104 disaggregase is a critical mechanism to protect the latent protein synthesis machinery during quiescence in yeast, ensuring the rapid restart of translation once nutrients are replenished. |
| first_indexed | 2024-03-08T16:16:17Z |
| format | Article |
| id | doaj.art-5dbf4037911449959b5703bfa8fbcbd3 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T16:16:17Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-5dbf4037911449959b5703bfa8fbcbd32024-01-07T12:35:18ZengNature PortfolioNature Communications2041-17232024-01-0115112010.1038/s41467-023-44538-8Nuclear Hsp104 safeguards the dormant translation machinery during quiescenceVerena Kohler0Andreas Kohler1Lisa Larsson Berglund2Xinxin Hao3Sarah Gersing4Axel Imhof5Thomas Nyström6Johanna L. Höög7Martin Ott8Claes Andréasson9Sabrina Büttner10Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityInstitute of Molecular Biosciences, University of GrazDepartment of Chemistry and Molecular Biology, University of GothenburgDepartment of Microbiology and Immunology, University of GothenburgThe Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of CopenhagenBiomedical Center Munich, Faculty of Medicine, Ludwig Maximilian University of MunichDepartment of Microbiology and Immunology, University of GothenburgDepartment of Chemistry and Molecular Biology, University of GothenburgDepartment of Biochemistry and Biophysics, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityAbstract The resilience of cellular proteostasis declines with age, which drives protein aggregation and compromises viability. The nucleus has emerged as a key quality control compartment that handles misfolded proteins produced by the cytosolic protein biosynthesis system. Here, we find that age-associated metabolic cues target the yeast protein disaggregase Hsp104 to the nucleus to maintain a functional nuclear proteome during quiescence. The switch to respiratory metabolism and the accompanying decrease in translation rates direct cytosolic Hsp104 to the nucleus to interact with latent translation initiation factor eIF2 and to suppress protein aggregation. Hindering Hsp104 from entering the nucleus in quiescent cells results in delayed re-entry into the cell cycle due to compromised resumption of protein synthesis. In sum, we report that cytosolic-nuclear partitioning of the Hsp104 disaggregase is a critical mechanism to protect the latent protein synthesis machinery during quiescence in yeast, ensuring the rapid restart of translation once nutrients are replenished.https://doi.org/10.1038/s41467-023-44538-8 |
| spellingShingle | Verena Kohler Andreas Kohler Lisa Larsson Berglund Xinxin Hao Sarah Gersing Axel Imhof Thomas Nyström Johanna L. Höög Martin Ott Claes Andréasson Sabrina Büttner Nuclear Hsp104 safeguards the dormant translation machinery during quiescence Nature Communications |
| title | Nuclear Hsp104 safeguards the dormant translation machinery during quiescence |
| title_full | Nuclear Hsp104 safeguards the dormant translation machinery during quiescence |
| title_fullStr | Nuclear Hsp104 safeguards the dormant translation machinery during quiescence |
| title_full_unstemmed | Nuclear Hsp104 safeguards the dormant translation machinery during quiescence |
| title_short | Nuclear Hsp104 safeguards the dormant translation machinery during quiescence |
| title_sort | nuclear hsp104 safeguards the dormant translation machinery during quiescence |
| url | https://doi.org/10.1038/s41467-023-44538-8 |
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