Multistability maintains redox homeostasis in human cells

Abstract Cells metabolize nutrients through a complex metabolic and signaling network that governs redox homeostasis. At the core of this, redox regulatory network is a mutually inhibitory relationship between reduced glutathione and reactive oxygen species (ROS)—two opposing metabolites that are li...

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Autores principales:	Jo‐Hsi Huang, Hannah KC Co, Yi‐Chen Lee, Chia‐Chou Wu, Sheng‐hong Chen
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	bistability glucose deprivation redox homeostasis Biology (General) QH301-705.5 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/60475745a9364f34bc3dd705e2085422
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spelling	oai:doaj.org-article:60475745a9364f34bc3dd705e20854222021-11-11T11:30:47ZMultistability maintains redox homeostasis in human cells1744-429210.15252/msb.202110480https://doaj.org/article/60475745a9364f34bc3dd705e20854222021-10-01T00:00:00Zhttps://doi.org/10.15252/msb.202110480https://doaj.org/toc/1744-4292Abstract Cells metabolize nutrients through a complex metabolic and signaling network that governs redox homeostasis. At the core of this, redox regulatory network is a mutually inhibitory relationship between reduced glutathione and reactive oxygen species (ROS)—two opposing metabolites that are linked to upstream nutrient metabolic pathways (glucose, cysteine, and glutamine) and downstream feedback loops of signaling pathways (calcium and NADPH oxidase). We developed a nutrient‐redox model of human cells to understand system‐level properties of this network. Combining in silico modeling and ROS measurements in individual cells, we show that ROS dynamics follow a switch‐like, all‐or‐none response upon glucose deprivation at a threshold that is approximately two orders of magnitude lower than its physiological concentration. We also confirm that this ROS switch can be irreversible and exhibits hysteresis, a hallmark of bistability. Our findings evidence that bistability modulates redox homeostasis in human cells and provide a general framework for quantitative investigations of redox regulation in humans.Jo‐Hsi HuangHannah KC CoYi‐Chen LeeChia‐Chou WuSheng‐hong ChenWileyarticlebistabilityglucose deprivationredox homeostasisBiology (General)QH301-705.5Medicine (General)R5-920ENMolecular Systems Biology, Vol 17, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bistability glucose deprivation redox homeostasis Biology (General) QH301-705.5 Medicine (General) R5-920
spellingShingle	bistability glucose deprivation redox homeostasis Biology (General) QH301-705.5 Medicine (General) R5-920 Jo‐Hsi Huang Hannah KC Co Yi‐Chen Lee Chia‐Chou Wu Sheng‐hong Chen Multistability maintains redox homeostasis in human cells
description	Abstract Cells metabolize nutrients through a complex metabolic and signaling network that governs redox homeostasis. At the core of this, redox regulatory network is a mutually inhibitory relationship between reduced glutathione and reactive oxygen species (ROS)—two opposing metabolites that are linked to upstream nutrient metabolic pathways (glucose, cysteine, and glutamine) and downstream feedback loops of signaling pathways (calcium and NADPH oxidase). We developed a nutrient‐redox model of human cells to understand system‐level properties of this network. Combining in silico modeling and ROS measurements in individual cells, we show that ROS dynamics follow a switch‐like, all‐or‐none response upon glucose deprivation at a threshold that is approximately two orders of magnitude lower than its physiological concentration. We also confirm that this ROS switch can be irreversible and exhibits hysteresis, a hallmark of bistability. Our findings evidence that bistability modulates redox homeostasis in human cells and provide a general framework for quantitative investigations of redox regulation in humans.
format	article
author	Jo‐Hsi Huang Hannah KC Co Yi‐Chen Lee Chia‐Chou Wu Sheng‐hong Chen
author_facet	Jo‐Hsi Huang Hannah KC Co Yi‐Chen Lee Chia‐Chou Wu Sheng‐hong Chen
author_sort	Jo‐Hsi Huang
title	Multistability maintains redox homeostasis in human cells
title_short	Multistability maintains redox homeostasis in human cells
title_full	Multistability maintains redox homeostasis in human cells
title_fullStr	Multistability maintains redox homeostasis in human cells
title_full_unstemmed	Multistability maintains redox homeostasis in human cells
title_sort	multistability maintains redox homeostasis in human cells
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/60475745a9364f34bc3dd705e2085422
work_keys_str_mv	AT johsihuang multistabilitymaintainsredoxhomeostasisinhumancells AT hannahkcco multistabilitymaintainsredoxhomeostasisinhumancells AT yichenlee multistabilitymaintainsredoxhomeostasisinhumancells AT chiachouwu multistabilitymaintainsredoxhomeostasisinhumancells AT shenghongchen multistabilitymaintainsredoxhomeostasisinhumancells
_version_	1718439129057853440

Multistability maintains redox homeostasis in human cells

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