IRE1 coordinates UPR and ERAD pathways to maintain protein homeostasis under ER stress in Arabidopsis

Environmental stress in plants often leads to the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), triggering the unfolded protein response (UPR) and ER-associated degradation (ERAD) to restore protein homeostasis. In Arabidopsis, the ER stress sensor IRE1 catalyzes the unconventional splicing of bZIP60 mRNA, producing a transcription factor that regulates UPR-related genes. However, the role of IRE1 in ERAD regulation remains unclear. Here, we demonstrate that ire1a&b double mutants show delayed induction of key ERAD components, including HRD1B, EBS5/HRD3, and EBS6/OS9, under tunicamycin-induced ER stress. In a genetic background carrying the misfolded brassinosteroid receptor Bri1-5, loss of IRE1 exacerbates dwarfism and increases the stability of Bri1-5 protein, indicating impaired ERAD activity. Overexpression of Bri1-5 in the ire1a&b background phenocopied the dwarf and stress-sensitive traits, confirming the role of IRE1 in mitigating ERAD substrate accumulation. Chemical inhibition experiments further revealed that proper glycoprotein processing and degradation are essential for normal growth and stress tolerance, and that IRE1 function is critical for coordinating these processes. Our findings uncover a key regulatory function of IRE1 in linking the UPR and ERAD pathways, thereby maintaining ER homeostasis and supporting plant growth under stress conditions.