ArticleScience signaling2018
Mitochondrial redox sensing by the kinase ATM maintains cellular antioxidant capacity.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Biomarkers in Ataxia-Telangiectasia: a Systematic Review.Journal of neurology · 2025Pooled it
- Stem cell models in ataxia-telangiectasia.Neural regeneration research · 2026Article
- The meiotic achilles' heel: vulnerability and resilience under environmental stress.Protoplasma · 2026Review
- ReDisulphID: A discovery platform for thiol redox sensors identifies a druggable site regulating p53 activation.Redox biology · 2026Article
- Autoinflammatory syndromes of STING and TREX1 dysfunction.The Journal of clinical investigation · 2026Review
- Targeting the FNIP2-SERCA2b axis improves metabolic and mitochondrial defects in Ataxia Telangiectasia.Cell death & disease · 2026Article
- Attenuation of ATM signaling by ROS delays replicative senescence at physiological oxygen.Molecular cell · 2025Article
- PRDX1 protects ATM from arsenite-induced proteotoxicity and maintains its stability during DNA damage signaling.Oncotarget · 2025Article
- ATM knock out alters calcium signalling and augments contraction in skeletal muscle cells differentiated from human urine-derived stem cells.Cell death discovery · 2025Article
- Review
- ATM in immunobiology: From lymphocyte development to cancer immunotherapy.Translational oncology · 2025Review
- Increased exercise tolerance in humanized G6PD-deficient mice.Blood advances · 2025Article
- "Dissecting the role of T cell exhaustion in cancer progression: a multifaceted approach".Frontiers in immunology · 2025Review
- Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025Review
- Somatic mutations in angiogenesis-related pathways and RNA polymerase II activity in sporadic brain arteriovenous malformations.Frontiers in neurology · 2025Article
- Tumour reoxygenation after intratumoural hydrogen peroxide (KORTUC) injection: a novel approach to enhance radiosensitivity.BJC reports · 2024Article
- A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization.Acta pharmaceutica Sinica. B · 2024Article
- ATM-deficiency-induced microglial activation promotes neurodegeneration in ataxia-telangiectasia.Cell reports · 2024Article
- Altered Regulation of the Glucose Transporter GLUT3 in PRDX1 Null Cells Caused Hypersensitivity to Arsenite.Cells · 2023Article
- Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
Mitochondria are integral to cellular energy metabolism and ATP production and are involved in regulating many cellular processes. Mitochondria produce reactive oxygen species (ROS), which not only can damage cellular components but also participate in signal transduction. The kinase ATM, which is mutated in the neurodegenerative, autosomal recessive disease ataxia-telangiectasia (A-T), is a key player in the nuclear DNA damage response. However, ATM also performs a redox-sensing function mediated through formation of ROS-dependent disulfide-linked dimers. We found that mitochondria-derived hydrogen peroxide promoted ATM dimerization. In HeLa cells, ATM dimers were localized to the nucleus and inhibited by the redox regulatory protein thioredoxin 1 (TRX1), suggesting the existence of a ROS-mediated, stress-signaling relay from mitochondria to the nucleus. ATM dimer formation did not affect its association with chromatin in the absence or presence of nuclear DNA damage, consistent with the separation of its redox and DNA damage signaling functions. Comparative analysis of U2OS cells expressing either wild-type ATM or the redox sensing-deficient C2991L mutant revealed that one function of ATM redox sensing is to promote glucose flux through the pentose phosphate pathway (PPP) by increasing the abundance and activity of glucose-6-phosphate dehydrogenase (G6PD), thereby increasing cellular antioxidant capacity. The PPP produces the coenzyme NADPH needed for a robust antioxidant response, including the regeneration of TRX1, indicating the existence of a regulatory feedback loop involving ATM and TRX1. We propose that loss of the mitochondrial ROS-sensing function of ATM may cause cellular ROS accumulation and oxidative stress in A-T.
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Registered trials
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.