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Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events
Although autophagy is a type of programmed cell death, it is also essential for cell survival upon tolerable level of various stress events. For the cell to respond adequately to an external and/or internal stimulus induced by cellular stress, autophagy must be controlled in a highly regulated manne...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988068/ https://www.ncbi.nlm.nih.gov/pubmed/33758166 http://dx.doi.org/10.1038/s41419-021-03599-7 |
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author | Kapuy, Orsolya Holczer, Marianna Márton, Margita Korcsmáros, Tamás |
author_facet | Kapuy, Orsolya Holczer, Marianna Márton, Margita Korcsmáros, Tamás |
author_sort | Kapuy, Orsolya |
collection | PubMed |
description | Although autophagy is a type of programmed cell death, it is also essential for cell survival upon tolerable level of various stress events. For the cell to respond adequately to an external and/or internal stimulus induced by cellular stress, autophagy must be controlled in a highly regulated manner. By using systems biology techniques, here we explore the dynamical features of autophagy induction. We propose that the switch-like characteristic of autophagy induction is achieved by a control network, containing essential feedback loops of four components, so-called autophagy inducer, autophagy controller, mTORC1 and autophagy executor, respectively. We show how an autophagy inducer is capable to turn on autophagy in a cellular stress-specific way. The autophagy controller acts as a molecular switch and not only promotes autophagy but also blocks the permanent hyperactivation of the process via downregulating the autophagy inducer. In this theoretical analysis, we explore in detail the properties of all four proposed controlling elements and their connections. Here we also prove that the kinetic features of this control network can be considered accurate in various stress processes (such as starvation, endoplasmic reticulum stress and oxidative stress), even if the exact components may be different. The robust response of the resulting control network is essential during cellular stress. |
format | Online Article Text |
id | pubmed-7988068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79880682021-04-16 Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events Kapuy, Orsolya Holczer, Marianna Márton, Margita Korcsmáros, Tamás Cell Death Dis Article Although autophagy is a type of programmed cell death, it is also essential for cell survival upon tolerable level of various stress events. For the cell to respond adequately to an external and/or internal stimulus induced by cellular stress, autophagy must be controlled in a highly regulated manner. By using systems biology techniques, here we explore the dynamical features of autophagy induction. We propose that the switch-like characteristic of autophagy induction is achieved by a control network, containing essential feedback loops of four components, so-called autophagy inducer, autophagy controller, mTORC1 and autophagy executor, respectively. We show how an autophagy inducer is capable to turn on autophagy in a cellular stress-specific way. The autophagy controller acts as a molecular switch and not only promotes autophagy but also blocks the permanent hyperactivation of the process via downregulating the autophagy inducer. In this theoretical analysis, we explore in detail the properties of all four proposed controlling elements and their connections. Here we also prove that the kinetic features of this control network can be considered accurate in various stress processes (such as starvation, endoplasmic reticulum stress and oxidative stress), even if the exact components may be different. The robust response of the resulting control network is essential during cellular stress. Nature Publishing Group UK 2021-03-23 /pmc/articles/PMC7988068/ /pubmed/33758166 http://dx.doi.org/10.1038/s41419-021-03599-7 Text en © The Author(s) 2021 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/. |
spellingShingle | Article Kapuy, Orsolya Holczer, Marianna Márton, Margita Korcsmáros, Tamás Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events |
title | Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events |
title_full | Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events |
title_fullStr | Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events |
title_full_unstemmed | Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events |
title_short | Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events |
title_sort | autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988068/ https://www.ncbi.nlm.nih.gov/pubmed/33758166 http://dx.doi.org/10.1038/s41419-021-03599-7 |
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