Nuclear Hsp104 safeguards the dormant translation machinery during quiescence
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Nuclear Hsp104 safeguards the dormant translation machinery during quiescence. / Kohler, Verena; Kohler, Andreas; Berglund, Lisa Larsson; Hao, Xinxin; Gersing, Sarah; Imhof, Axel; Nyström, Thomas; Höög, Johanna L.; Ott, Martin; Andréasson, Claes; Büttner, Sabrina.
I: Nature Communications, Bind 15, Nr. 1, 315, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Nuclear Hsp104 safeguards the dormant translation machinery during quiescence
AU - Kohler, Verena
AU - Kohler, Andreas
AU - Berglund, Lisa Larsson
AU - Hao, Xinxin
AU - Gersing, Sarah
AU - Imhof, Axel
AU - Nyström, Thomas
AU - Höög, Johanna L.
AU - Ott, Martin
AU - Andréasson, Claes
AU - Büttner, Sabrina
N1 - Publisher Copyright: © 2024, The Author(s).
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-023-44538-8
DO - 10.1038/s41467-023-44538-8
M3 - Journal article
C2 - 38182580
AN - SCOPUS:85181445502
VL - 15
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 315
ER -
ID: 379650356