Hsp104-Hsp70-Hsp110 chaperones disintegrate kinase aggregates formed upon stress in Saccharomyces cerevisiae.

The cellular protein quality control (PQC) machinery maintains proteostasis. However, knowledge of PQC machinery-mediated handling of stress-induced misfolded proteins is still insufficient. We used the yeast kinase Ste11 to observe its fate upon heat stress or Hsp90 inhibition. We observed that while mild heat stress (37 °C) primarily resulted in proteasomal degradation of Ste11, severe heat stress (42 °C) resulted predominantly in aggregation. Ste11 aggregates sequestered with Hsp42 upon heat stress or Hsp90 inhibition. These aggregates associate with Hsp70 and Hsp104, the yeast disaggregase machinery. Notably, Ste11 aggregates disappear upon recovery from stress. This phenomenon is impaired in the absence of Hsp104 or Sse1, a co-chaperone recruited to the aggregates by Hsp70, suggesting the involvement of Hsp104, Hsp70 and Sse1 in aggregate mobilisation.