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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 unloads the cytosolic protein biosynthesis system from misfolded proteins. 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 subcomplexes 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, ensuring the rapid restart of translation once nutrients are replenished.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Ignasi Forne

LAB HEAD: Sabrina Büttner

PROVIDER: PXD042987 | Pride | 2024-01-12

REPOSITORIES: Pride

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	BioID_sample_names_PXD042987_20230807.xlsx	Xlsx
	Ref4995_MO_01_20210319.raw	Raw
	Ref4995_MO_02_20210319.raw	Raw
	Ref4995_MO_03_20210319.raw	Raw
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