ArticleMolecular systems biology2021
Multistability maintains redox homeostasis in human cells.
Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
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- Identification of an Anoikis-Related Gene Signature to Predict the Prognosis in Patients With Oral Squamous Cell Carcinoma.International dental journal · 2026Article
- Origins of Ultrasensitivity and Complex Signaling Dynamics of Cellular Hydrogen Peroxide and Peroxiredoxin.Antioxidants (Basel, Switzerland) · 2025Article
- Metabolic Reprogramming at the Edge of Redox: Connections Between Metabolic Reprogramming and Cancer Redox State.International journal of molecular sciences · 2025Review
- Mechanisms and therapeutic potential of disulphidptosis in cancer.Cell proliferation · 2025Review
- Ten "Cheat Codes" for Measuring Oxidative Stress in Humans.Antioxidants (Basel, Switzerland) · 2024Review
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- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Intimate intertwining of the pathogenesis of hypoxia and systemic sclerosis: A transcriptome integration analysis.Frontiers in immunology · 2022Article
- Multistability maintains redox homeostasis in human cells.Molecular systems biology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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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Registered trials
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