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TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress
The endoplasmic reticulum (ER) is an organelle of nucleated cells that produces proteins, lipids and oligosaccharides. ER volume and activity are increased upon induction of unfolded protein responses (UPR) and are reduced upon activation of ER-phagy programs. A specialized domain of the ER, the nuc...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264389/ https://www.ncbi.nlm.nih.gov/pubmed/37311770 http://dx.doi.org/10.1038/s41467-023-39172-3 |
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author | Kucińska, Marika K. Fedry, Juliette Galli, Carmela Morone, Diego Raimondi, Andrea Soldà, Tatiana Förster, Friedrich Molinari, Maurizio |
author_facet | Kucińska, Marika K. Fedry, Juliette Galli, Carmela Morone, Diego Raimondi, Andrea Soldà, Tatiana Förster, Friedrich Molinari, Maurizio |
author_sort | Kucińska, Marika K. |
collection | PubMed |
description | The endoplasmic reticulum (ER) is an organelle of nucleated cells that produces proteins, lipids and oligosaccharides. ER volume and activity are increased upon induction of unfolded protein responses (UPR) and are reduced upon activation of ER-phagy programs. A specialized domain of the ER, the nuclear envelope (NE), protects the cell genome with two juxtaposed lipid bilayers, the inner and outer nuclear membranes (INM and ONM) separated by the perinuclear space (PNS). Here we report that expansion of the mammalian ER upon homeostatic perturbations results in TMX4 reductase-driven disassembly of the LINC complexes connecting INM and ONM and in ONM swelling. The physiologic distance between ONM and INM is restored, upon resolution of the ER stress, by asymmetric autophagy of the NE, which involves the LC3 lipidation machinery, the autophagy receptor SEC62 and the direct capture of ONM-derived vesicles by degradative LAMP1/RAB7-positive endolysosomes in a catabolic pathway mechanistically defined as micro-ONM-phagy. |
format | Online Article Text |
id | pubmed-10264389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102643892023-06-15 TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress Kucińska, Marika K. Fedry, Juliette Galli, Carmela Morone, Diego Raimondi, Andrea Soldà, Tatiana Förster, Friedrich Molinari, Maurizio Nat Commun Article The endoplasmic reticulum (ER) is an organelle of nucleated cells that produces proteins, lipids and oligosaccharides. ER volume and activity are increased upon induction of unfolded protein responses (UPR) and are reduced upon activation of ER-phagy programs. A specialized domain of the ER, the nuclear envelope (NE), protects the cell genome with two juxtaposed lipid bilayers, the inner and outer nuclear membranes (INM and ONM) separated by the perinuclear space (PNS). Here we report that expansion of the mammalian ER upon homeostatic perturbations results in TMX4 reductase-driven disassembly of the LINC complexes connecting INM and ONM and in ONM swelling. The physiologic distance between ONM and INM is restored, upon resolution of the ER stress, by asymmetric autophagy of the NE, which involves the LC3 lipidation machinery, the autophagy receptor SEC62 and the direct capture of ONM-derived vesicles by degradative LAMP1/RAB7-positive endolysosomes in a catabolic pathway mechanistically defined as micro-ONM-phagy. Nature Publishing Group UK 2023-06-13 /pmc/articles/PMC10264389/ /pubmed/37311770 http://dx.doi.org/10.1038/s41467-023-39172-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Kucińska, Marika K. Fedry, Juliette Galli, Carmela Morone, Diego Raimondi, Andrea Soldà, Tatiana Förster, Friedrich Molinari, Maurizio TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress |
title | TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress |
title_full | TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress |
title_fullStr | TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress |
title_full_unstemmed | TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress |
title_short | TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress |
title_sort | tmx4-driven linc complex disassembly and asymmetric autophagy of the nuclear envelope upon acute er stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264389/ https://www.ncbi.nlm.nih.gov/pubmed/37311770 http://dx.doi.org/10.1038/s41467-023-39172-3 |
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