ArticleCellular and molecular life sciences : CMLS2022
AUF1 protects against ferroptosis to alleviate sepsis-induced acute lung injury by regulating NRF2 and ATF3.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 94 citations in OpenAlex.
- Ferroptosis-Senescence Crosstalk in Sepsis-Associated Acute Lung Injury: Mechanisms and Therapeutic Opportunities.Biomedicines · 2026Review
- NIR-responsive prussian Blue/Fer-1 co-loaded nanozymes for synergistic therapy of acute lung injury.Journal of nanobiotechnology · 2026Article
- YTHDF1 mediates KLF2/VSIG4 axis to regulate Kupffer cell polarization to alleviate sepsis-induced liver injury.Genes and immunity · 2026Article
- STUB1 stabilizes sirtuin 6 via K63-linked ubiquitination to promote NRF2 deacetylation for enhanced ferroptosis resistance after spinal cord injury.Burns & trauma · 2026Article
- Ferroptosis-associated changes in transfusion-related acute lung injury in Sprague Dawley rats.Open medicine (Warsaw, Poland) · 2026Article
- Sepsis-induced acute lung injury: AUF1 regulates pyroptosis via ETS2/ZDHHC21-mediated STING palmitoylation : A therapeutic target for lung injury.Cellular and molecular life sciences : CMLS · 2025Article
- Inhalable targeted CD8 + T cell nanoparticles loaded ferroptosis inhibitor ferrostatin-1 alleviate acute lung injury.Journal of nanobiotechnology · 2025Article
- The ferroptosis-related gene MAFG screened by machine learning is associated with the diagnosis and prognosis of sepsis.Clinical and experimental medicine · 2025Article
- DCTPP1 regulates oxidative stress homeostasis via AUF1 in human villous trophoblasts.Cell death discovery · 2025Article
- Sirt4 Overexpression Modulates the JAK2/STAT3 and PI3K/AKT/mTOR Axes to Alleviate Sepsis-Induced Acute Lung Injury.Cell biochemistry and biophysics · 2025Article
- FBXW7-Mediated Downregulation of GPX4 Aggravates Acute Kidney Injury Following Ischemia‒Reperfusion.Inflammation · 2025Article
- The P2XPurinergic signalling · 2025Article
- Advances in acute respiratory distress syndrome: focusing on heterogeneity, pathophysiology, and therapeutic strategies.Signal transduction and targeted therapy · 2025Review
- Advancements in omics technologies: Molecular mechanisms of acute lung injury and acute respiratory distress syndrome (Review).International journal of molecular medicine · 2025Review
- Mechanism of Ferroptosis and Its Role in Disease Development.International journal of biological sciences · 2025Review
- SIRT5-mediated HOXA5 desuccinylation inhibits ferroptosis to alleviate sepsis induced-lung injury.The Kaohsiung journal of medical sciences · 2025Article
- Overcoming Ferroptosis-Induced Exhaustion of NK Cells through Inhibition of the ATF3-Mediated Integrated Stress Response in Ovarian Cancer.International journal of biological sciences · 2025Article
- The molecular and metabolic landscape of ferroptosis in respiratory diseases: Pharmacological aspects.Journal of pharmaceutical analysis · 2025Review
- Construction of a novel gene signature linked to ferroptosis in pediatric sepsis.Frontiers in cell and developmental biology · 2025Article
- Ferroptosis: a key driver and therapeutic target in the pathogenesis of acute respiratory distress syndrome.Frontiers in immunology · 2025Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe AU-rich element (ARE)-binding factor 1 (AUF1) acts as a switch for septic shock, although its underlying mechanisms remain largely unknown. In this study, we examined the biological significance and potential molecular mechanism of AUF1 in regulating ferroptosis in sepsis-induced acute lung injury (ALI).
methodsAlveolar epithelial cells (AECs) challenged with ferroptosis-inducing compounds and cecum ligation and puncture (CLP)-induced ALI were used as the in vitro and in vivo model, respectively. The stability of AUF1 and its degradation by ubiquitin-proteasome pathway were examined by cycloheximide chase analysis and co-immunoprecipitation assay. The regulation of AUF1 on nuclear factor E2-related factor 2 (NRF2) and activation transcription factor 3 (ATF3) was explored by RNA immunoprecipitation (RIP), RNA pull-down, and mRNA stability assays. Functionally, the effects of altering AUF1, NRF2 or ATF3 on ferroptosis in AECs or ALI mice were evaluated by measuring cell viability, lipid peroxidation, iron accumulation, and total glutathione level.
resultsAUF1 was down-regulated in AECs challenged with ferroptosis-inducing compounds, both on mRNA and protein levels. The E3 ubiquitin ligase FBXW7 was responsible for protein degradation of AUF1 during ferroptosis. By up-regulating NRF2 and down-regulating ATF3, AUF1 antagonized ferroptosis in AECs in vitro. In the CLP-induced ALI model, the survival rate of AUF1 knockout mice was significantly reduced and the lung injuries were aggravated, which were related to the enhancement of lung ferroptosis.
conclusionsFBXW7 mediates the ubiquitination and degradation of AUF1 in ferroptosis. AUF1 antagonizes ferroptosis by regulating NRF2 and ATF3 oppositely. Activating AUF1 pathway may be beneficial to the treatment of sepsis-induced ALI.
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