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Nuclear Hsp104 safeguards the dormant translation machinery during quiescence

Author

Listed:
  • Verena Kohler

    (Stockholm University
    University of Graz
    Umeå University)

  • Andreas Kohler

    (University of Graz
    Stockholm University
    Umeå University)

  • Lisa Larsson Berglund

    (University of Gothenburg)

  • Xinxin Hao

    (University of Gothenburg)

  • Sarah Gersing

    (University of Copenhagen)

  • Axel Imhof

    (Ludwig Maximilian University of Munich)

  • Thomas Nyström

    (University of Gothenburg)

  • Johanna L. Höög

    (University of Gothenburg)

  • Martin Ott

    (Stockholm University
    University of Gothenburg)

  • Claes Andréasson

    (Stockholm University)

  • Sabrina Büttner

    (Stockholm University)

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.

Suggested Citation

  • Verena Kohler & Andreas Kohler & Lisa Larsson Berglund & Xinxin Hao & Sarah Gersing & Axel Imhof & Thomas Nyström & Johanna L. Höög & Martin Ott & Claes Andréasson & Sabrina Büttner, 2024. "Nuclear Hsp104 safeguards the dormant translation machinery during quiescence," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44538-8
    DOI: 10.1038/s41467-023-44538-8
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    References listed on IDEAS

    as
    1. F. Ulrich Hartl & Andreas Bracher & Manajit Hayer-Hartl, 2011. "Molecular chaperones in protein folding and proteostasis," Nature, Nature, vol. 475(7356), pages 324-332, July.
    2. Won-Ki Huh & James V. Falvo & Luke C. Gerke & Adam S. Carroll & Russell W. Howson & Jonathan S. Weissman & Erin K. O'Shea, 2003. "Global analysis of protein localization in budding yeast," Nature, Nature, vol. 425(6959), pages 686-691, October.
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