Multistability maintains redox homeostasis in human cells |
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| Authors: | Jo&#x;Hsi Huang Hannah KC Co Yi&#x;Chen Lee Chia&#x;Chou Wu Sheng&#x;hong Chen |
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| Institution: | 1. Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford CA, USA ; 2. Institute of Molecular Biology, Academia Sinica, Taipei Taiwan ; 3. Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Science, National Defense Medical Center, Taipei Taiwan ; 4. Genome and Systems Biology Degree Program, Academia Sinica and National Taiwan University, Taipei Taiwan |
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| 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. |
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| Keywords: | bistability glucose deprivation redox homeostasis |
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