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Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events

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Title: Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events
Authors: Kapuy, O
Holczer, M
Marton, M
Korcsmaros, T
Item Type: Journal Article
Abstract: 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.
Issue Date: 23-Mar-2021
Date of Acceptance: 25-Feb-2021
URI: http://hdl.handle.net/10044/1/94348
DOI: 10.1038/s41419-021-03599-7
ISSN: 2041-4889
Publisher: Nature Publishing Group
Start Page: 1
End Page: 11
Journal / Book Title: Cell Death and Disease
Volume: 12
Issue: 4
Copyright Statement: © 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/.
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Cell Survival
Stress, Physiological
Cell Survival
Stress, Physiological
Science & Technology
Life Sciences & Biomedicine
Cell Biology
0601 Biochemistry and Cell Biology
1112 Oncology and Carcinogenesis
Publication Status: Published
Article Number: ARTN 309
Online Publication Date: 2021-03-23
Appears in Collections:Department of Metabolism, Digestion and Reproduction

This item is licensed under a Creative Commons License Creative Commons