ArticleScientific reports2016
Iron mitigates DMT1-mediated manganese cytotoxicity via the ASK1-JNK signaling axis: Implications of iron supplementation for manganese toxicity.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Overlaps in mammalian iron and manganese homeostasis: recent advances.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- The interplay of iron status and manganese biomarkers in U.S. females: NHANES 2015-2018 analysis.Metallomics : integrated biometal science · 2025Article
- Studies of Slc30a10 Deficiency in Mice Reveal That Intestinal Iron Transporters Dmt1 and Ferroportin Transport Manganese.Cellular and molecular gastroenterology and hepatology · 2025Article
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- [Research progress on metal pollutants inducing neurotoxicity through ferroptosis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- In vitro reconstitution of transition metal transporters.The Journal of biological chemistry · 2024Review
- Manganese transporter SLC30A10 and iron transporters SLC40A1 and SLC11A2 impact dietary manganese absorption.bioRxiv : the preprint server for biology · 2024Article
- Olfactory tract/bulb metal concentration in Manganese-exposed mineworkers.Neurotoxicology · 2024Article
- Differences and Interactions in Placental Manganese and Iron Transfer across an In Vitro Model of Human Villous Trophoblasts.International journal of molecular sciences · 2022Article
- Parkinson's Disease and the Metal-Microbiome-Gut-Brain Axis: A Systems Toxicology Approach.Antioxidants (Basel, Switzerland) · 2021Review
- Air pollutants disrupt iron homeostasis to impact oxidant generation, biological effects, and tissue injury.Free radical biology & medicine · 2020Review
- The effects of manganese overexposure on brain health.Neurochemistry international · 2020Review
- Manganese Acts upon Insulin/IGF Receptors to Phosphorylate AKT and Increase Glucose Uptake in Huntington's Disease Cells.Molecular neurobiology · 2020Article
- Acute manganese treatment restores defective autophagic cargo loading in Huntington's disease cell lines.Human molecular genetics · 2019Article
- Manganese causes neurotoxic iron accumulation via translational repression of amyloid precursor protein and H-Ferritin.Journal of neurochemistry · 2018Article
- Physiological and Biochemical Effects of Echium Amoenum Extract on MnAdvanced pharmaceutical bulletin · 2018Article
- Neurotoxicity Linked to Dysfunctional Metal Ion Homeostasis and Xenobiotic Metal Exposure: Redox Signaling and Oxidative Stress.Antioxidants & redox signaling · 2018Review
- A FTH1 gene:pseudogene:microRNA network regulates tumorigenesis in prostate cancer.Nucleic acids research · 2018Article
- Affected energy metabolism under manganese stress governs cellular toxicity.Scientific reports · 2017Article
- Transgenic Mice Overexpressing the Divalent Metal Transporter 1 Exhibit Iron Accumulation and Enhanced Parkin Expression in the Brain.Neuromolecular medicine · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Manganese (Mn(2+)) neurotoxicity from occupational exposure is well documented to result in a Parkinson-like syndrome. Although the understanding of Mn(2+) cytotoxicity is still incomplete, both Mn(2+) and Fe(2+) can be transported via the divalent metal transporter 1 (DMT1), suggesting that competitive uptake might disrupt Fe(2+) homeostasis. Here, we found that DMT1 overexpression significantly enhanced Mn(2+) cytoplasmic accumulation and JNK phosphorylation, leading to a reduction in cell viability. Although a robust activation of autophagy was observed alongside these changes, it did not trigger autophagic cell death, but was instead shown to be essential for the degradation of ferritin, which normally sequesters labile Fe(2+). Inhibition of ferritin degradation through the neutralization of lysosomal pH resulted in increased ferritin and enhanced cytoplasmic Fe(2+) depletion. Similarly, direct Fe(2+) chelation also resulted in aggravated Mn(2+)-mediated JNK phosphorylation, while Fe(2+) repletion protected cells, and this occurs via the ASK1-thioredoxin pathway. Taken together, our study presents the novel findings that Mn(2+) cytotoxicity involves the depletion of the cytoplasmic Fe(2+) pool, and the increase in autophagy-lysosome activity is important to maintain Fe(2+) homeostasis. Thus, Fe(2+) supplementation could have potential applications in the prevention and treatment of Mn(2+)-mediated toxicity.
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