# New insights into Sti1/Hop's cochaperone function highlight the complexity of proteostatic regulation

## TL;DR

Sti1/Hop, a cochaperone, helps manage misfolded proteins during stress, revealing a new role beyond its traditional function in chaperone complexes.

## Contribution

The study reveals that Sti1/Hop sequesters misfolded proteins during stress, extending its function beyond scaffolding chaperone complexes.

## Key findings

- Sti1/Hop sequesters misfolded proteins in the cytoplasm during high stress.
- Sti1/Hop's localization and levels are crucial for proper proteostasis under stress.
- Imbalances in Sti1/Hop levels affect cellular fitness and stress resilience.

## Abstract

Sti1/Hop is a cochaperone that regulates Hsp70 and Hsp90 chaperones. Sti1/Hop function is perceived as limited to scaffolding chaperone complexes, although recent studies suggest a broader function. Rutledge et al. show that while Sti1/Hop functions within chaperone complexes under basal conditions, during high stress, it operates independently to sequester soluble misfolded protein in the cytoplasm, a function typically associated with chaperones rather than cochaperones. Furthermore, the localisation and levels of Sti1/Hop are finely tuned to ensure orderly sequestration and resolution of misfolded proteins. These data support a role for Sti1/Hop as a cochaperone specialised for stressed proteostasis networks.

Sti1/Hop functions extend beyond scaffolding in the Hsp70‐Hsp90 chaperone complex to sequester misfolded proteins during cell stress. Consequently, imbalances between levels of Sti1/Hop relative to the rest of the proteostasis machinery negatively affect fitness and stress resilience.