ArticleThe Journal of clinical investigation2017
Sirtuin 2 regulates cellular iron homeostasis via deacetylation of transcription factor NRF2.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Targeting ferroptosis unveils a new era for traditional Chinese medicine: a scientific metrology study.Frontiers in pharmacology · 2024Pooled it
- SIRT6-Mediated Deacetylation of ATF3 Promotes Silica-Induced Lung Fibrosis by Enhancing its Nuclear Import via Binding to Importin α.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Microglial SIRT6 confers protection against neuroinflammation-associated depression through NRF2-HO1 signaling.Neurobiology of stress · 2026Article
- Review
- Oxidative Stress andInternational journal of molecular sciences · 2026Review
- Iron regulation by Sirtuins 1 & 2 and their therapeutic modulation by Sirtinol.Frontiers in pharmacology · 2026Review
- Elucidating the role of SIRT2 in hepatocellular carcinoma through multi-omics and deep learning.Discover oncology · 2025Article
- Sirtuins as mediators and targets of arsenic toxicity: unraveling signaling pathway crosstalk.Archives of toxicology · 2025Review
- Iron-sensitive RNA regulation by poly C-binding proteins.Nucleic acids research · 2025Article
- Modulating nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in liver-brain axis disorders.World journal of psychiatry · 2025Review
- Regulatory Dynamics of Nrf2 With Sirtuins in the Brain: Exploring Cellular Metabolism, Synaptic Plasticity, and Defense Mechanisms.Journal of neurochemistry · 2025Review
- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- TaHSP18.6 and TaSRT1 interact to confer resistance toProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sirtuins Contribute to the Migraine-Stroke Connection.International journal of molecular sciences · 2025Review
- Hydroxycitric acid inhibits ferroptosis and ameliorates benign prostatic hyperplasia by upregulating the Nrf2/GPX4 pathway.World journal of urology · 2025Article
- SIRT7-mediated NRF2 deacetylation promotes antioxidant response and protects against chemodrug-induced liver injury.Cell death & disease · 2025Article
- Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects.Bone research · 2025Review
- Electroacupuncture attenuates ferroptosis by promoting Nrf2 nuclear translocation and activating Nrf2/SLC7A11/GPX4 pathway in ischemic stroke.Chinese medicine · 2025Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
SIRT2 is a cytoplasmic sirtuin that plays a role in various cellular processes, including tumorigenesis, metabolism, and inflammation. Since these processes require iron, we hypothesized that SIRT2 directly regulates cellular iron homeostasis. Here, we have demonstrated that SIRT2 depletion results in a decrease in cellular iron levels both in vitro and in vivo. Mechanistically, we determined that SIRT2 maintains cellular iron levels by binding to and deacetylating nuclear factor erythroid-derived 2-related factor 2 (NRF2) on lysines 506 and 508, leading to a reduction in total and nuclear NRF2 levels. The reduction in nuclear NRF2 leads to reduced ferroportin 1 (FPN1) expression, which in turn results in decreased cellular iron export. Finally, we observed that Sirt2 deletion reduced cell viability in response to iron deficiency. Moreover, livers from Sirt2-/- mice had decreased iron levels, while this effect was reversed in Sirt2-/- Nrf2-/- double-KO mice. Taken together, our results uncover a link between sirtuin proteins and direct control over cellular iron homeostasis via regulation of NRF2 deacetylation and stability.
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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.