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

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.