Emerging Principles of Selective ER Autophagy

Abstract

The endoplasmic reticulum (ER) is a fundamental organelle in cellular metabolism and signal transduction. It is subject to complex, dynamic sculpting of morphology and composition. Degradation of ER content has an important role to play here. Indeed, a major emerging player in ER turnover is ER-phagy, the degradation of ER fragments by selective autophagy, particularly macroautophagy. This article proposes a number of unifying principles of ER-phagy mechanism and compares these with other selective autophagy pathways. A perspective on the likely roles of ER-phagy in determining cell fate is provided. Emerging related forms of intracellular catabolism of the ER or contents, including ER-phagy by microautophagy and selective ER protein removal via the lysosome, are outlined for comparison. Unresolved questions regarding the mechanism of ER-phagy and its significance in cellular and organismal health are put forward. This review concludes with a perspective on how this fundamental knowledge might inform future clinical developments.

Graphical abstract

Highlights

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  ER-phagy selectively degrades fragments of ER via the macroautophagy pathway.

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  ER membrane localized cargo receptors bind the ER to core autophagy proteins.

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  ER-phagy requires ER reshaping and may be selective for sub-ER content.

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  Different receptors link stress signals to differential degradation of ER content.

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  ER-phagy controls the pathogenesis of diseases including infection and cancer.