Sti1 participates in the dynamics of protein aggregation triggered by glucose signaling in Saccharomyces cerevisiae.

Environmental changes put stress on living organisms. We find that nutrient starvation induces dynamic protein aggregations in yeast cells, and many chaperones are involved in this process. Among them, Sti1/HOP, the co-chaperone of Hsp70 and Hsp90, plays roles in the formation of protein quality control (PQC) compartments and protein stasis (or proteostasis) maintenance, and it co-localizes to insoluble protein deposits (IPOD) by liquid-liquid phase separation (LLPS). Notably, the subcellular localization and cytoplasmic aggregation of Sti1 are rigorously regulated by the PQC machinery, including Ssa1/Hsp70 and Hsp82/Hsp90. On the other hand, STI1 deletion abolishes cytoplasmic aggregation of chaperones, including Ssa1, Hsp42, and Hsp104. These results reveal an interdependent model of chaperone-mediated aggregate formation. Furthermore, lysine 9 (K9) of Sti1 is identified as a critical residue governing its cytoplasmic condensation through a potential post-translational modification.