ArticleCell death & disease2024
Targeting SIRT3 sensitizes glioblastoma to ferroptosis by promoting mitophagy and inhibiting SLC7A11.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 56 citations in OpenAlex.
- A transferrin receptor-targeted liposome for iron metabolism regulation-augmented photodynamic therapy in glioblastoma.Bioactive materials · 2027Article
- Circular RNAs in ferroptosis regulation and tumor progression of gynecological and breast cancers: molecular mechanisms and therapeutic potential.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- CXCL8 Enhances Malignancy of GBM via TNFα-NFκB Mediated Suppression of Ferroptosis.Applied biochemistry and biotechnology · 2026Article
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Targeting the miR-19b/PPP2R5E axis enhances temozolomide response in glioblastoma via ROS-induced DNA damage.British journal of cancer · 2026Article
- Article
- Targeting Ferroptosis in Glioblastoma: Molecular Mechanisms, Tumor Microenvironment, and Therapeutic Opportunities.Cancers · 2026Review
- Provoking disulfidptosis-enhanced mitophagy by manganese-based nanoplatform via regulating cellular energy supply and redox homeostasis.Materials today. Bio · 2026Article
- Proteomic and Metabolomic Profiling Reveal Mitochondrial Transplantation-Mediated Reprogramming in Gastric Cancer Cells.The Kaohsiung journal of medical sciences · 2026Article
- The dual function of mitophagy in ferroptosis.Biophysics reports · 2026Article
- Review
- Targeting PTDSS1 to modulate GSH synthesis triggers mitophagy and induces ferroptosis in esophageal squamous cell carcinoma cells.Cell death & disease · 2026Article
- Identification of Pinostilbene as a natural STING agonist that triggers FTH1 degradation via K48-ubiquitination to induce ferroptosis in non-small cell lung cancer.Redox biology · 2026Article
- Decoding ferroptosis and apoptosis crosstalk in glioblastoma: molecular mechanisms, microenvironmental regulation, and therapeutic advances.Molecular biology reports · 2026Review
- Ferroptosis in Glioblastoma and Neuroblastoma: Molecular Mechanisms and Novel Therapeutic Strategies.Current issues in molecular biology · 2026Review
- Mitochondrial Calcium Uniporter Drives Chemoresistance in Pancreatic Cancer via Glutathione-Mediated Stemness Maintenance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Paeoniflorin alleviates hypobaric hypoxia-triggered lung injury through targeting MEK2 to modulate ERK2-SGK1 signaling.Acta pharmaceutica Sinica. B · 2026Article
- Ferroptosis-autophagy crosstalk in bladder cancer: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
Abstract
Glioblastoma (GBM) cells require large amounts of iron for tumor growth and progression, which makes these cells vulnerable to destruction via ferroptosis induction. Mitochondria are critical for iron metabolism and ferroptosis. Sirtuin-3 (SIRT3) is a deacetylase found in mitochondria that regulates mitochondrial quality and function. This study aimed to characterize SIRT3 expression and activity in GBM and investigate the potential therapeutic effects of targeting SIRT3 while also inducing ferroptosis in these cells. We first found that SIRT3 expression was higher in GBM tissues than in normal brain tissues and that SIRT3 protein expression was upregulated during RAS-selective lethal 3 (RSL3)-induced GBM cell ferroptosis. We then observed that inhibition of SIRT3 expression and activity in GBM cells sensitized GBM cells to RSL3-induced ferroptosis both in vitro and in vivo. Mechanistically, SIRT3 inhibition led to ferrous iron and ROS accumulation in the mitochondria, which triggered mitophagy. RNA-Sequencing analysis revealed that upon SIRT3 knockdown in GBM cells, the mitophagy pathway was upregulated and SLC7A11, a critical antagonist of ferroptosis via cellular import of cystine for glutathione (GSH) synthesis, was downregulated. Forced expression of SLC7A11 in GBM cells with SIRT3 knockdown restored cellular cystine uptake and consequently the cellular GSH level, thereby partially rescuing cell viability upon RSL3 treatment. Furthermore, in GBM cells, SIRT3 regulated SLC7A11 transcription through ATF4. Overall, our study results elucidated novel mechanisms underlying the ability of SIRT3 to protect GBM from ferroptosis and provided insight into a potential combinatorial approach of targeting SIRT3 and inducing ferroptosis for GBM treatment.
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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.