Manganese homeostasis: from rare single-gene disorders to complex phenotypes and diseases
Nathan Katz, Daniel J. Rader
Nathan Katz, Daniel J. Rader
Published November 4, 2019
Citation Information: J Clin Invest. 2019;129(12):5082-5085. https://doi.org/10.1172/JCI133120.
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Commentary

Manganese homeostasis: from rare single-gene disorders to complex phenotypes and diseases

Abstract

Manganese (Mn) participates in a variety of distinct physiological processes, including acting as a cofactor for several enzymes and metalloenzymes, in addition to playing a role in immune function, endocrine function, hematopoiesis, and oxidative stress regulation. Mn homeostasis is tightly regulated via intestinal absorption and hepatobiliary and intestinal excretion. In this issue of the JCI, Mercadante and colleagues explored the role of the metal transporter Slc30a10 in vivo using a mouse model system. The authors used whole-body and tissue-specific gene knockouts to show that Slc30a10 is paramount for Mn excretion in the liver and small intestines. These findings provide further insights into mechanisms for Mn homeostasis as well as potential targets for addressing Mn-associated disorders or environmental exposures.

Authors

Nathan Katz, Daniel J. Rader

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Figure 1

Model for Mn homeostasis with a focus on excretion pathways.

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Model for Mn homeostasis with a focus on excretion pathways. Systemic Mn...
Systemic Mn homeostasis is largely regulated by pathways of Mn excretion in hepatocytes and enterocytes. (i) Mn uptake from blood by hepatocytes is mediated by SLC39A14 at the basolateral membrane. Mn excretion from hepatocytes into bile is mediated by SLC30A10 at the canalicular membrane. (ii) Mn reuptake from bile into hepatocytes is mediated by SLC39A8 also at the canalicular membrane. Biliary Mn ultimately arrives in the intestinal lumen and, if not reabsorbed (not shown), is excreted in the feces. (iii) In addition, Mn is taken up from blood by enterocytes via SLC39A14 at the basolateral membrane and effluxed into the lumen by SLC30A10 at the apical surface. This figure does not show absorption of Mn via uptake pathways from the gut lumen into enterocytes and blood.