ArticleProceedings of the National Academy of Sciences of the United States of America2015
A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 66 citations in OpenAlex.
- Broiler Ascites Syndrome as a Potential Spontaneous Animal Model for Human Pulmonary Arterial Hypertension: A Narrative Review.Life (Basel, Switzerland) · 2026Review
- Mitochondrial Calcium Uniporter Regulates ITAM-Dependent Platelet Activation.Circulation research · 2025Article
- Stem cell-like reprogramming is required for leukemia-initiating activity in B-ALL.The Journal of experimental medicine · 2024Article
- AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived HJournal of Cancer · 2024Article
- Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition.Cancer research · 2023Article
- Opposite Effect of Thyroid Hormones on Oxidative Stress and on Mitochondrial Respiration in COVID-19 Patients.Antioxidants (Basel, Switzerland) · 2022Article
- Ascorbate synthesis as an alternative electron source for mitochondrial respiration: Possible implications for the plant performance.Frontiers in plant science · 2022Review
- Ubiquitin-like processing of TUG proteins as a mechanism to regulate glucose uptake and energy metabolism in fat and muscle.Frontiers in endocrinology · 2022Review
- Novel role of xanthine oxidase-dependent HRedox biology · 2021Article
- Single-cell intracellular epitope and transcript detection reveals signal transduction dynamics.Cell reports methods · 2021Article
- Shear and Integrin Outside-In Signaling Activate NADPH-Oxidase 2 to Promote Platelet Activation.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- The Mia40/CHCHD4 Oxidative Folding System: Redox Regulation and Signaling in the Mitochondrial Intermembrane Space.Antioxidants (Basel, Switzerland) · 2021Review
- Embryo and Its Mitochondria.Antioxidants (Basel, Switzerland) · 2021Review
- Review
- BAFF attenuates oxidative stress-induced cell death by the regulation of mitochondria membrane potential via Syk activation in WiL2-NS B lymphoblasts.Scientific reports · 2020Article
- Immunoglobulin expression in the endoplasmic reticulum shapes the metabolic fitness of B lymphocytes.Life science alliance · 2020Article
- Iron and Cadmium Entry Into Renal Mitochondria: Physiological and Toxicological Implications.Frontiers in cell and developmental biology · 2020Review
- Muscle and adipose tissue insulin resistance: malady without mechanism?Journal of lipid research · 2019Review
- Phosphoregulation on mitochondria: Integration of cell and organelle responses.CNS neuroscience & therapeutics · 2019Review
- The GTPase Rab1 Is Required for NLRP3 Inflammasome Activation and Inflammatory Lung Injury.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 8 institutions in 2 countries.
Funding
Abstract
Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) govern cellular homeostasis by inducing signaling. H2O2 modulates the activity of phosphatases and many other signaling molecules through oxidation of critical cysteine residues, which led to the notion that initiation of ROS signaling is broad and nonspecific, and thus fundamentally distinct from other signaling pathways. Here, we report that H2O2 signaling bears hallmarks of a regular signal transduction cascade. It is controlled by hierarchical signaling events resulting in a focused response as the results place the mitochondrial respiratory chain upstream of tyrosine-protein kinase Lyn, Lyn upstream of tyrosine-protein kinase SYK (Syk), and Syk upstream of numerous targets involved in signaling, transcription, translation, metabolism, and cell cycle regulation. The active mediators of H2O2 signaling colocalize as H2O2 induces mitochondria-associated Lyn and Syk phosphorylation, and a pool of Lyn and Syk reside in the mitochondrial intermembrane space. Finally, the same intermediaries control the signaling response in tissues and species responsive to H2O2 as the respiratory chain, Lyn, and Syk were similarly required for H2O2 signaling in mouse B cells, fibroblasts, and chicken DT40 B cells. Consistent with a broad role, the Syk pathway is coexpressed across tissues, is of early metazoan origin, and displays evidence of evolutionary constraint in the human. These results suggest that H2O2 signaling is under control of a signal transduction pathway that links the respiratory chain to the mitochondrial intermembrane space-localized, ubiquitous, and ancient Syk pathway in hematopoietic and nonhematopoietic cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.