Manganese metabolism in humans
- Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER)Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER) stress, autophagy dysregulation, apoptosis, and disruption of other metal homeostasis. The mechanisms of Mn homeostasis are not fully understood. Here, we will address recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells. We will conclude with recommendations for future research areas on Mn metabolism.…
Author details: | Pan Chen, Julia BornhorstORCiDGND, Michael AschnerORCiDGND |
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DOI: | https://doi.org/10.2741/4665 |
ISSN: | 1093-9946 |
ISSN: | 1093-4715 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/29293455 |
Title of parent work (English): | Frontiers in Bioscience-Landmark |
Publisher: | Frontiers in Bioscience INC |
Place of publishing: | Irvine |
Publication type: | Article |
Language: | English |
Date of first publication: | 2018/03/01 |
Publication year: | 2018 |
Release date: | 2022/01/11 |
Tag: | Blood-Brain Barrier; Homeostasis; Manganese; Metal Metabolism; Neurotoxicity; Review; Transporters |
Volume: | 23 |
Issue: | 9 |
Number of pages: | 25 |
First page: | 1655 |
Last Page: | 1679 |
Funding institution: | NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIEHS R01 10563]; "Deutsche Forschungsgemeinschaft" (DFG)German Research Foundation (DFG) [BO 4103/2-1]; TraceAge - DFG Research Unit on Interactions of essential trace elements in healthy and diseased elderly, Potsdam-Berlin-Jena [FOR 2558/1] |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Peer review: | Referiert |
Publishing method: | Open Access / Green Open-Access |
License (German): | CC-BY - Namensnennung 4.0 International |
External remark: | Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 711 |