ER-to-lysosome-associated degradation in a nutshell: mammalian, yeast, and plant ER-phagy as induced by misfolded proteins

Conserved catabolic pathways operate to remove aberrant polypeptides from the endoplasmic reticulum (ER), the major biosynthetic organelle of eukaryotic cells. The best known are the ER-associated degradation (ERAD) pathways that control the retrotranslocation of terminally misfolded proteins across the ER membrane for clearance by the cytoplasmic ubiquitin/proteasome system. In this review, we catalog folding-defective mammalian, yeast, and plant proteins that fail to engage ERAD machineries. We describe that they rather segregate in ER subdomains that eventually vesiculate. These ER-derived vesicles are captured by double membrane autophagosomes, engulfed by endolysosomes/vacuoles, or fused with degradative organelles to clear cells from their toxic cargo. These client-specific, mechanistically diverse ER-phagy pathways are grouped under the umbrella term of ER-to-lysosome-associated degradation for description in this essay.

Automated summary

Conserved catabolic pathways operate to remove aberrant polypeptides from the endoplasmic reticulum (ER), utilizing ERAD pathways and ER-phagy. ERAD pathways control retrotranslocation of misfolded proteins across the ER membrane, while ER-phagy segregates proteins into ER subdomains that eventually vesiculate. These ER-derived vesicles can be captured by autophagosomes, endolysosomes/vacuoles, or fused with degradative organelles.