Abstract
Governed by the unfolded protein response (UPR), the ability to counteract endoplasmic reticulum (ER) stress is critical for maintaining cellular homeostasis under adverse conditions. Unresolved ER stress leads to cell death through mechanisms that are yet not completely known. To identify key UPR effectors involved in unresolved ER stress, we performed an ethyl methanesulfonate (EMS) suppressor screen on the Arabidopsis bzip28/60 mutant, which is impaired in activating cytoprotective UPR pathways. This screen identified MAP kinase organizer 1 (MORG1), a conserved MAP kinase scaffold protein, as a previously uncharacterized regulator of ER stress tolerance. The coffin1 mutant, which carries a mutation in MORG1 , exhibited enhanced resilience to ER stress by partially restoring UPR gene expression and promoting growth under stress conditions. Mechanistically, we found that MORG1 modulates MPK6-dependent phosphorylation of the stress-responsive transcription factor WRKY8. Loss of WRKY8 phenocopied the coffin1 mutant, highlighting WRKY8's role as a key repressor in the UPR. Together, these findings reveal a MORG1-MPK6-WRKY8 signaling axis that fine-tunes UPR gene expression, providing new insights into ER stress regulation and strategies for improving stress tolerance in multicellular eukaryotes.