ArticleEMBO reports2019
Iron overload inhibits late stage autophagic flux leading to insulin resistance.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 93 citations in OpenAlex.
- Association of iron status with gestational diabetes and preeclampsia in an obesogenic context: Results from a cohort of pregnant Chilean women.European journal of clinical nutrition · 2026Article
- Associative Analysis of lncRNA/circRNA-miRNA-mRNA Expression Profiles in Iron-Overloaded HT-1080 Fibrosarcoma Cells.International journal of molecular sciences · 2026Article
- Crosstalk between autophagy and ferroptosis in liver diseases (Review).International journal of molecular medicine · 2026Review
- Article
- Mitochondrial iron overload is associated with lysosomal dysfunction-mediated mitophagy impairment in the heart of Friedreich's ataxia.Mitochondrion · 2026Article
- High Dietary Carbonyl Iron Reshapes the Gut Microbiome and Impairs Hepatic Insulin Sensitivity in a Time-Dependent Manner.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Downregulation of SLC40A1 leads to iron accumulation in fibrotic lung fibroblasts.Respiratory research · 2026Article
- Autophagy related biomarkers in ulcerative colitis revealed by bioinformatics analysis and immune correlation.Scientific reports · 2025Article
- Metals in the human liver: An underappreciated risk factor of hepatic insulin resistance and associated pathophysiology.Environmental pollution (Barking, Essex : 1987) · 2025Review
- Article
- Hydrogen Sulfide (HAntioxidants (Basel, Switzerland) · 2025Article
- Muscle mTOR controls iron homeostasis and ferritinophagy via NRF2, HIFs and AKT/PKB signaling pathways.Cellular and molecular life sciences : CMLS · 2025Article
- Sex-specific skeletal muscle gene expression responses to exercise reveal novel direct mediators of insulin sensitivity change.NAR molecular medicine · 2025Article
- Research on the Relationship Between Ectopic Fat and Iron Deposition in the Liver and Pancreas, with Glucose Metabolism in Elderly Obese Patients.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Combined effects of maternal supplementation of iron, calcium, folic acid, and multivitamin during pregnancy on obesity in Chinese preschoolers born macrosomia.Frontiers in pediatrics · 2025Article
- Exercise regulates mitophagy to alleviate parkinsonian neurodegeneration.Frontiers in aging neuroscience · 2025Review
- The Impact of Iron Homeostasis in Insulin-Sensitive Tissues and Gut Microbiome on Obesity-Driven Metabolic Disorders.Advances in experimental medicine and biology · 2025Review
- Lysosome-Iron-Mitochondria Axis in Osteoclasts: Iron as a Central Player.Research (Washington, D.C.) · 2025Review
- Donepezil improves skeletal muscle insulin resistance in obese mice via the AMPK/FGF21-mediated suppression of inflammation and ferroptosis.Archives of pharmacal research · 2024Article
- The Association Between Dietary Iron, the SNP of the JAZF1 rs864745, and Glucose Metabolism in a Chinese Population.Nutrients · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Iron overload, a common clinical occurrence, is implicated in the metabolic syndrome although the contributing pathophysiological mechanisms are not fully defined. We show that prolonged iron overload results in an autophagy defect associated with accumulation of dysfunctional autolysosomes and loss of free lysosomes in skeletal muscle. These autophagy defects contribute to impaired insulin-stimulated glucose uptake and insulin signaling. Mechanistically, we show that iron overload leads to a decrease in Akt-mediated repression of tuberous sclerosis complex (TSC2) and Rheb-mediated mTORC1 activation on autolysosomes, thereby inhibiting autophagic-lysosome regeneration. Constitutive activation of mTORC1 or iron withdrawal replenishes lysosomal pools via increased mTORC1-UVRAG signaling, which restores insulin sensitivity. Induction of iron overload via intravenous iron-dextran delivery in mice also results in insulin resistance accompanied by abnormal autophagosome accumulation, lysosomal loss, and decreased mTORC1-UVRAG signaling in muscle. Collectively, our results show that chronic iron overload leads to a profound autophagy defect through mTORC1-UVRAG inhibition and provides new mechanistic insight into metabolic syndrome-associated insulin resistance.
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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.