ArticleThe Journal of biological chemistry2013
Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor-initiated signal transduction.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Ferroptosis in T cells: mechanisms, biology and translational opportunities.Nature reviews. Immunology · 2026Review
- Review
- Extracellular Redox Balance as a Determinant of Immune Regulation and Tissue Inflammation.Antioxidants (Basel, Switzerland) · 2026Review
- Pyruvate kinase muscle 2 (PKM2) promotes CD4 T cell survival by regulating pyruvate oxidation during homeostasis and expansion.Science advances · 2026Article
- Mitochondria reactive oxygen species signaling-dependent immune responses in macrophages and T cells.Immunity · 2025Review
- Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway.Molecules (Basel, Switzerland) · 2024Article
- Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The relationship of redox signaling with the risk for atherosclerosis.Frontiers in pharmacology · 2024Review
- Manganese Superoxide Dismutase Acetylation and Regulation of Protein Structure in Breast Cancer Biology and Therapy.Antioxidants (Basel, Switzerland) · 2022Review
- Divalent Metal Uptake and the Role of ZIP8 in Host Defense Against Pathogens.Frontiers in cell and developmental biology · 2022Review
- Electrochemical Measurements Reveal Reactive Oxygen Species in Stress Granules*.Angewandte Chemie (International ed. in English) · 2021Article
- Complement's favourite organelle-Mitochondria?British journal of pharmacology · 2021Review
- The Redox-Metabolic Couple of T Lymphocytes: Potential Consequences for Hypertension.Antioxidants & redox signaling · 2021Review
- Metabolic ROS Signaling: To Immunity and Beyond.Biochemistry. Biokhimiia · 2020Review
- CTRP3 Activates the AMPK/SIRT1-PGC-1α Pathway to Protect Mitochondrial Biogenesis and Functions in Cerebral Ischemic Stroke.Neurochemical research · 2020Article
- Metformin enhances protection in guinea pigs chronically infected with Mycobacterium tuberculosis.Scientific reports · 2020Article
- Age-associated changes in human CD4Aging · 2019Article
- Review
- Ndufs2, a Core Subunit of Mitochondrial Complex I, Is Essential for Acute Oxygen-Sensing and Hypoxic Pulmonary Vasoconstriction.Circulation research · 2019Article
- Codonopsis lanceolata attenuates allergic lung inflammation by inhibiting Th2 cell activation and augmenting mitochondrial ROS dismutase (SOD2) expression.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
T cell receptor (TCR)-initiated signal transduction is reported to increase production of intracellular reactive oxygen species, such as superoxide (O2˙(-)) and hydrogen peroxide (H2O2), as second messengers. Although H2O2 can modulate signal transduction by inactivating protein phosphatases, the mechanism and the subcellular localization of intracellular H2O2 as a second messenger of the TCR are not known. The antioxidant enzyme superoxide dismutase (SOD) catalyzes the dismutation of highly reactive O2˙(-) into H2O2 and thus acts as an intracellular generator of H2O2. As charged O2˙(-) is unable to diffuse through intracellular membranes, cells express distinct SOD isoforms in the cytosol (Cu,Zn-SOD) and mitochondria (Mn-SOD), where they locally scavenge O2˙(-) leading to production of H2O2. A 2-fold organelle-specific overexpression of either SOD in Jurkat T cell lines increases intracellular production of H2O2 but does not alter the levels of intracellular H2O2 scavenging enzymes such as catalase, membrane-bound peroxiredoxin1 (Prx1), and cytosolic Prx2. We report that overexpression of Mn-SOD enhances tyrosine phosphorylation of TCR-associated membrane proximal signal transduction molecules Lck, LAT, ZAP70, PLCγ1, and SLP76 within 1 min of TCR cross-linking. This increase in mitochondrial H2O2 specifically modulates MAPK signaling through the JNK/cJun pathway, whereas overexpressing Cu,Zn-SOD had no effect on any of these TCR-mediated signaling molecules. As mitochondria translocate to the immunological synapse during TCR activation, we hypothesize this translocation provides the effective concentration of H2O2 required to selectively modulate downstream signal transduction pathways.
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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.