ArticleProceedings of the National Academy of Sciences of the United States of America2014
Inhibition of p53 preserves Parkin-mediated mitophagy and pancreatic β-cell function in diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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Who cites it
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 210 citations in OpenAlex.
- Systematic review on biomarker potential of vitreous microRNA in retinal disease.Frontiers in ophthalmology · 2025Pooled it
- Metformin Ameliorates Diabetes-Associated Cognitive Dysfunction via p53/Parkin-Mediated Mitophagy.Diabetes, obesity & metabolism · 2026Article
- AS160 Overexpression Protects Against β-Cell Failure in Hyperglycemic Mice by Interacting With HSPA8 to Regulate Mitophagy.Acta physiologica (Oxford, England) · 2026Article
- Mitophagy and Noncoding RNA Regulation in Type 2 Diabetes Mellitus: Molecular Mechanisms, Tissue-Specific Evidence and Translational Perspective.Biomedicines · 2026Review
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Elevated MANF expression in β cells protects mice from streptozotocin-induced diabetes by attenuating islet stress and immunogenicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Mitochondrial Homeostasis in Pancreatic β Cell Function: Mechanisms and Therapeutic Targets for Diabetes.Journal of diabetes · 2026Review
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Review
- Advances and challenges in modeling Charcot-Marie-Tooth type 2A using iPSC-derived models.Stem cell reports · 2025Review
- Olivomycin A Targets Epithelial-Mesenchymal Transition, Apoptosis, and Mitochondrial Quality Control in Renal Cancer Cells.Antioxidants (Basel, Switzerland) · 2025Article
- The interplay of tumor suppressor p53 and oxidative stress in pancreatic β-cell apoptosis and insulin resistance in newly diagnosed type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2025Article
- TRAF6 integrates innate immune signals to regulate glucose homeostasis via Parkin-dependent and Parkin-independent mitophagy.Science advances · 2025Article
- DNA repair protein RAD50 is involved in the streptozotocin-induced diabetes susceptibility of mice.Experimental animals · 2025Article
- Genomic correlation, shared loci, and causal link between obesity and diabetic microvascular complications: A genome-wide pleiotropic analysis.Biomolecules & biomedicine · 2025Article
- The Balance of MFN2 and OPA1 in Mitochondrial Dynamics, Cellular Homeostasis, and Disease.Biomolecules · 2025Review
- Implication of Bimodal Magnetic Resonance and Fluorescence Imaging Probes in Advanced Healthcare: Enhancing Disease Diagnosis and Targeted Therapy.International journal of nanomedicine · 2025Review
- The role of short-chain fatty acid in metabolic syndrome and its complications: focusing on immunity and inflammation.Frontiers in immunology · 2025Review
- The mitochondrial enzyme pyruvate carboxylase restricts pancreatic β-cell senescence by blocking p53 activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- cNPAS2 induced β cell dysfunction by regulating KANK1 expression in type 2 diabetes.World journal of diabetes · 2024Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial compromise is a fundamental contributor to pancreatic β-cell failure in diabetes. Previous studies have demonstrated a broader role for tumor suppressor p53 that extends to the modulation of mitochondrial homeostasis. However, the role of islet p53 in glucose homeostasis has not yet been evaluated. Here we show that p53 deficiency protects against the development of diabetes in streptozotocin (STZ)-induced type 1 and db/db mouse models of type 2 diabetes. Glucolipotoxicity stimulates NADPH oxidase via receptor for advanced-glycation end products and Toll-like receptor 4. This oxidative stress induces the accumulation of p53 in the cytosolic compartment of pancreatic β-cells in concert with endoplasmic reticulum stress. Cytosolic p53 disturbs the process of mitophagy through an inhibitory interaction with Parkin and induces mitochondrial dysfunction. The occurrence of mitophagy is maintained in STZ-treated p53(-/-) mice that exhibit preserved glucose oxidation capacity and subsequent insulin secretion signaling, leading to better glucose tolerance. These protective effects are not observed when Parkin is deleted. Furthermore, pifithrin-α, a specific inhibitor of p53, ameliorates mitochondrial dysfunction and glucose intolerance in both STZ-treated and db/db mice. Thus, an intervention with cytosolic p53 for a mitophagy deficiency may be a therapeutic strategy for the prevention and treatment of diabetes.
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