1. Academic Validation
  2. Multistability maintains redox homeostasis in human cells

Multistability maintains redox homeostasis in human cells

  • Mol Syst Biol. 2021 Oct;17(10):e10480. doi: 10.15252/msb.202110480.
Jo-Hsi Huang 1 Hannah Kc Co 2 3 Yi-Chen Lee 2 Chia-Chou Wu 2 Sheng-Hong Chen 2 3 4
Affiliations

Affiliations

  • 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.
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.

Keywords

bistability; glucose deprivation; redox homeostasis.

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