Biochemical Society transactionsMay 27, 2018

Selective Recycling of the Cell's Protein-Making and Recovery Systems

Updated Feb 15, 2026

Abstract

The endoplasmic reticulum (ER) is essential for synthesizing proteins, lipids, and other molecules while managing calcium storage and detoxification.

ER volume and activity must be adjusted during stress and recovery phases to maintain cellular function.
involves the fragmentation of ER and delivery of its parts to lysosomes for degradation.
This process is critical for maintaining cellular balance in proteins, lipids, and oligosaccharides.
ER turnover is triggered by factors such as ER stress, nutrient scarcity, and the presence of misfolded proteins.
Specific proteins at the ER membrane act as receptors that help target ER fragments for autophagic degradation.

Simplified

The endoplasmic reticulum (ER) is the site of protein, lipid, phospholipid, steroid and oligosaccharide synthesis and modification, calcium ion storage, and detoxification of endogenous and exogenous products. Its volume (and activity) must be maintained under normal growth conditions, must be expanded in a controlled manner on activation of ER stress programs and must be reduced to pre-stress size during the recovery phase that follows ER stress termination. is the constitutive or regulated fragmentation and delivery of ER fragments to lysosomal compartments for clearance. It gives essential contribution to the maintenance of cellular homeostasis, proteostasis, lipidostasis and oligosaccharidostasis (i.e. the capacity to produce the proteome, lipidome and oligosaccharidome in appropriate quality and quantity). ER turnover is activated on ER stress, nutrient deprivation, accumulation of misfolded polypeptides, pathogen attack and by activators of macroautophagy. The selectivity of these poorly characterized catabolic pathways is ensured by proteins displayed at the limiting membrane of the ER subdomain to be removed from cells. These proteins are defined as ER-phagy receptors and engage the cytosolic macroautophagy machinery via specific modules that associate with ubiquitin-like, cytosolic proteins of the Atg8/LC3/GABARAP family. In this review, we give an overview on selective ER turnover and on the yeast and mammalian ER-phagy receptors identified so far.

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Abstract

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