A chaperone pathway in protein disaggregation. Hsp26 alters the nature of protein aggregates to facilitate reactivation by Hsp104

Cellular protein folding is challenged by environ-mental stress and aging, which lead to aberrant pro-tein conformations and aggregation. One way to antag-onize the detrimental consequences of protein misfolding is to reactivate vital proteins from aggre-gates. In the yeast Saccharomyces cerevisiae, Hsp104 facilitates disaggregation and reactivates aggregated proteins with assistance from Hsp70 (Ssa1) and Hsp40 (Ydj1). The small heat shock proteins, Hsp26 and Hsp42, also function in the recovery of misfolded pro-teins and prevent aggregation in vitro, but their in vivo roles in protein homeostasis remain elusive. We ob-served that after a sublethal heat shock, a majority of Hsp26 becomes insoluble. Its return to the soluble state during recovery depends on the presence o