The Hrd1-Mediated ERAD Pathway in Plants: Conserved Principles and Plant-Specific Innovations

Endoplasmic reticulum-mediated protein quality control (ERQC) safeguards secretory pathway proteostasis by recognizing, retaining, repairing, and removing misfolded proteins, and is therefore essential for plant growth, development, and stress tolerance. This system relies on ER-associated degradation (ERAD), in which irreparably misfolded proteins are first recognized in the ER, then exported across the ER membrane to the cytosol, where they are ubiquitinated by ER membrane-anchored ubiquitin ligases, and subsequently degraded by the cytosolic proteasome. Studies in yeast and mammals have defined several conserved ERAD branches, including a multiprotein ERAD complex centered on the polytopic ER membrane E3 ligase HMG-CoA reductase degradation protein 1 (Hrd1), which integrates substrate recognition, membrane retrotranslocation, ubiquitin conjugation, and cytosolic extraction. Recent advances in Arabidopsis show that plants retain the core Hrd1 ERAD architecture while incorporating additional regulatory elements that adapt this machinery to plant-specific physiological demands. Genetic and biochemical analyses of misfolded receptor kinases and engineered substrates have uncovered conserved and plant-specific components of the plant Hrd1 complex, revealing how the plant ERAD pathway integrates ERQC with hormone signaling, stress adaptation, immune responses, and growth regulation. This review synthesizes recent advances in plant ERAD research and highlights key conceptual and mechanistic questions that remain to be resolved.