Manganese metabolism in humans

Pan Chen, Julia Bornhorst, Michael Aschner

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1655-1679
Number of pages25
JournalFrontiers in Bioscience - Landmark
Issue number9
StatePublished - Mar 1 2018


  • Blood-Brain Barrier
  • Homeostasis
  • Manganese
  • Metal Metabolism
  • Neurotoxicity
  • Review
  • Transporters

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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