Sse1, Hsp110 chaperone of yeast, controls the cellular fate during Endoplasmic Reticulum-stress

Sse1 is a cytosolic Hsp110 molecular chaperone of yeast, Saccharomyces cerevisiae . Its multifaceted roles in cellular protein homeostasis as Nucleotide Exchange Factor (NEF), as protein-disaggregase and as a Chaperone linked to Protein Synthesis (CLIPS), are well documented. In the currently study, we show that SSE1 genetically interacts with IRE1 and HAC1 , the Endoplasmic Reticulum-Unfolded Protein Response (ER-UPR) sensors implicating its role in ER protein homeostasis. Interestingly, absence of this chaperone imparts unusual resistance to tunicamycin-induced ER stress which depends on the intact Ire1-Hac1 mediated ER-UPR signalling. Furthermore, cells lacking SSE1 show ER-stress-responsive inefficient reorganization of translating ribosomes from polysomes to monosomes and increased monosome content that drive uninterrupted protein translation. In consequence, the kinetics of ER-UPR is starkly different in sse1 Δ strain where we show that stress response induction and restoration of homeostasis is prominently faster in contrast to the wildtype (WT) cells. Importantly, Sse1 plays a critical role in controlling the ER-stress mediated cell division arrest which is escaped in sse1 Δ strain during chronic tunicamycin stress. Consequently, sse1 Δ strain shows significantly higher cell viability in comparison to WT yeast, following short-term as well as long-term tunicamycin stress. In summary, we demonstrate a new role of Sse1 in ER protein homeostasis where the chaperone genetically interacts with ER-UPR pathway, controls the protein translation during ER stress and the kinetics of ER-UPR. More importantly, we show the crtical role of Sse1 in regulating the ER-stress-induced cell division arrest and cell death during global ER stress by tunicamycin. Author Summary Sse1 is a cytosolic Hsp110 molecular chaperone of yeast, Saccharomyces cerevisiae . It performs various functions as Nucleotide Exchange Factor (NEF), as a protein-disaggregase and as a Chaperone linked to Protein Synthesis (CLIPS) to maintain a healthy proteome in the cytosol. In the present study, we show that SSE1 is a critical player to maintain Endoplasmic Reticulum (ER) protein homeostasis. We report that SSE1 genetically interacts with the ER-Unfolded Protein Response (ER-UPR) sensors, IRE1 and HAC1 . In absence of SSE1, yeast cells gain unusual fitness to tunicamycin (Tm)-induced ER stress which depends on the functional Ire1-Hac1 mediated ER-UPR signalling. Furthermore, Sse1 controls the ribosomal organization during tunicamycin-induced ER-stress and in absence of the chaperone the amount of polysomes and monosmes are high leading to uninterrupted protein translation during ER stress. Consequently, sse1 Δ strain exhibits starkly different ER-UPR kinetics compared to wildtype (WT) cells. Importantly, our data reveal that cell division arrest and cell death due to Tm-induced ER-stress is critically controlled by Sse1.