Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.

The protein folding capacity of the endoplasmic reticulum (ER) is regulated by the unfolded protein response (UPR). The UPR senses unfolded proteins in the ER lumen and transmits that information to the cell nucleus, where it drives a transcriptional program that is tailored to re-establish homeosta...

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Main Authors: Sebastián Bernales, Kent L McDonald, Peter Walter
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2006-11-01
Series:PLoS Biology
Online Access:http://europepmc.org/articles/PMC1661684?pdf=render
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spelling doaj-3a241f79ed05421e93655c65f62bc30a2021-07-02T08:04:48ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852006-11-01412e42310.1371/journal.pbio.0040423Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.Sebastián BernalesKent L McDonaldPeter WalterThe protein folding capacity of the endoplasmic reticulum (ER) is regulated by the unfolded protein response (UPR). The UPR senses unfolded proteins in the ER lumen and transmits that information to the cell nucleus, where it drives a transcriptional program that is tailored to re-establish homeostasis. Using thin section electron microscopy, we found that yeast cells expand their ER volume at least 5-fold under UPR-inducing conditions. Surprisingly, we discovered that ER proliferation is accompanied by the formation of autophagosome-like structures that are densely and selectively packed with membrane stacks derived from the UPR-expanded ER. In analogy to pexophagy and mitophagy, which are autophagic processes that selectively sequester and degrade peroxisomes and mitochondria, the ER-specific autophagic process described utilizes several autophagy genes: they are induced by the UPR and are essential for the survival of cells subjected to severe ER stress. Intriguingly, cell survival does not require vacuolar proteases, indicating that ER sequestration into autophagosome-like structures, rather than their degradation, is the important step. Selective ER sequestration may help cells to maintain a new steady-state level of ER abundance even in the face of continuously accumulating unfolded proteins.http://europepmc.org/articles/PMC1661684?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Sebastián Bernales
Kent L McDonald
Peter Walter
spellingShingle Sebastián Bernales
Kent L McDonald
Peter Walter
Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.
PLoS Biology
author_facet Sebastián Bernales
Kent L McDonald
Peter Walter
author_sort Sebastián Bernales
title Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.
title_short Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.
title_full Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.
title_fullStr Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.
title_full_unstemmed Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.
title_sort autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.
publisher Public Library of Science (PLoS)
series PLoS Biology
issn 1544-9173
1545-7885
publishDate 2006-11-01
description The protein folding capacity of the endoplasmic reticulum (ER) is regulated by the unfolded protein response (UPR). The UPR senses unfolded proteins in the ER lumen and transmits that information to the cell nucleus, where it drives a transcriptional program that is tailored to re-establish homeostasis. Using thin section electron microscopy, we found that yeast cells expand their ER volume at least 5-fold under UPR-inducing conditions. Surprisingly, we discovered that ER proliferation is accompanied by the formation of autophagosome-like structures that are densely and selectively packed with membrane stacks derived from the UPR-expanded ER. In analogy to pexophagy and mitophagy, which are autophagic processes that selectively sequester and degrade peroxisomes and mitochondria, the ER-specific autophagic process described utilizes several autophagy genes: they are induced by the UPR and are essential for the survival of cells subjected to severe ER stress. Intriguingly, cell survival does not require vacuolar proteases, indicating that ER sequestration into autophagosome-like structures, rather than their degradation, is the important step. Selective ER sequestration may help cells to maintain a new steady-state level of ER abundance even in the face of continuously accumulating unfolded proteins.
url http://europepmc.org/articles/PMC1661684?pdf=render
work_keys_str_mv AT sebastianbernales autophagycounterbalancesendoplasmicreticulumexpansionduringtheunfoldedproteinresponse
AT kentlmcdonald autophagycounterbalancesendoplasmicreticulumexpansionduringtheunfoldedproteinresponse
AT peterwalter autophagycounterbalancesendoplasmicreticulumexpansionduringtheunfoldedproteinresponse
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