ArticleAntioxidants (Basel, Switzerland)2023
SIRT5 Activation and Inorganic Phosphate Binding Reduce Cancer Cell Vitality by Modulating Autophagy/Mitophagy and ROS.
Article in Antioxidants (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- SIRT4 positively regulates autophagy via ULK1, but independently of HDAC6 and OPA1.FEBS open bio · 2026Article
- Succinylation modification in diabetes and diabetic complications: Mechanisms and functions (Review).Molecular medicine reports · 2026Review
- Crosstalk between mitophagy and breast cancer: mechanisms of action and clinical applications.Journal of cancer research and clinical oncology · 2026Review
- Acute Hypoxia Induces Cardiomyocyte Autophagy via SIRT5/mTOR/ULK1 Pathway.BioMed research international · 2026Article
- Succinylation: novel molecular mechanisms and prospects for targeted therapy in liver diseases.Frontiers in molecular biosciences · 2026Review
- A Combined SIRT5 Activation and SIRT3 Inhibition Prevents Breast Cancer Spheroids Growth by Reducing HIF-1α and Mitophagy.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Sirtuins in Women's Health.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Resveratrol Alleviated Oxidative Damage of Bovine Mammary Epithelial Cells via Activating SIRT5-IDH2 Axis.Antioxidants (Basel, Switzerland) · 2025Article
- Carcinogenesis Associated with Toxin Nephropathy: Proposed Mediation by Phosphate Toxicity.Cells · 2025Review
- The clinical impact of mitochondrial autophagy on very late-onset recurrence after catheter ablation for atrial fibrillation.European heart journal open · 2025Article
- Sirtuins and tumor immunity: mechanistic insights, immunotherapy prospects, and therapeutic horizons.Frontiers in immunology · 2025Review
- Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development.Frontiers in immunology · 2025Review
- Cardioprotection Through Pharmacological Activation of Sirtuin 5 in a Murine Model of Acute Myocardial Infarction.Drug design, development and therapy · 2025Article
- SIRT5-Mediated Desuccinylation of RAB7A Protects Against Cadmium-Induced Alzheimer's Disease-Like Pathology by Restoring Autophagic Flux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Sirtuins Affect Cancer Stem Cells via Epigenetic Regulation of Autophagy.Biomedicines · 2024Review
- Targeting sirtuins for cancer therapy: epigenetics modifications and beyond.Theranostics · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer cells show increased glutamine consumption. The glutaminase (GLS) enzyme controls a limiting step in glutamine catabolism. Breast tumors, especially the triple-negative subtype, have a high expression of GLS. Our recent study demonstrated that GLS activity and ammonia production are inhibited by sirtuin 5 (SIRT5). We developed MC3138, a selective SIRT5 activator. Treatment with MC3138 mimicked the deacetylation effect mediated by SIRT5 overexpression. Moreover, GLS activity was regulated by inorganic phosphate (Pi). Considering the interconnected roles of GLS, SIRT5 and Pi in cancer growth, our hypothesis is that activation of SIRT5 and reduction in Pi could represent a valid antitumoral strategy. Treating cells with MC3138 and lanthanum acetate, a Pi chelator, decreased cell viability and clonogenicity. We also observed a modulation of MAP1LC3B and ULK1 with MC3138 and lanthanum acetate. Interestingly, inhibition of the mitophagy marker BNIP3 was observed only in the presence of MC3138. Autophagy and mitophagy modulation were accompanied by an increase in cytosolic and mitochondrial reactive oxygen species (ROS). In conclusion, our results show how SIRT5 activation and/or Pi binding can represent a valid strategy to inhibit cell proliferation by reducing glutamine metabolism and mitophagy, leading to a deleterious accumulation of ROS.
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What OpenQuestion holds
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.