Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity

Bile acid composition regulates the manganese transporter Slc30a10 in intestine

“…But the intestine appears to play an important role in Mn homeostasis as well, especially when liver excretion has been saturated (60). While deletion of Slc30a10 only in hepatocytes is insufficient to cause hypermanganesemia, combined deletion in liver and gastrointestinal tract causes severe hypermanganesemia and neurotoxicity (39,41), mimicking the whole-body Slc30a10 knockout mice, though less severe (39,40). These findings support the notion that intestine and hepatobiliary excretion systems both participate in Mn homeostasis.…”

Brain manganese and the balance between essential roles and neurotoxicity

“…Results from the double knockouts imply that activity of SLC39A14 is necessary to transport Mn into hepatocytes for subsequent excretion by SLC30A10 (Figure 3). While intestinal Mn levels were not analyzed in the double knockouts, the differential localization of SLC30A10 and SLC39A14 in enterocytes described above, data from tissue-specific Slc30a10 knockout mice (154,156), and recent findings showing that SLC39A14 is required for the transport of Mn from blood into enterocytes (176), put together, suggest that SLC30A10 and SLC39A14 likely also act cooperatively to mediate intestinal Mn excretion (Figure 3). We note an additional interesting feature about the Slc30a10/Slc39a14 double knockouts.…”

“…The above data suggest that lossof-function of SLC30A10 blocks Mn excretion, which leads to a build-up of Mn within the body, and the retained Mn accumulates in the brain to induce neurotoxicity (Figure 3). The excretory function of SLC30A10 was validated in 2019 using radioactive Mn excretion and surgical approaches (156).…”

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

“…In the current issue of the JCI, Mercadante et al provide data revealing the critical role of the Mn exporter SLC30A10, thus advancing our understanding of biliary Mn excretion (18). Mice deficient in whole-body Slc30A10 showed elevated blood and tissue Mn levels and, because of impaired biliary excretion of Mn, had (Figure 1) (18). SLC39A14 (ZIP14) is another Mn importer expressed in both hepatocytes and enterocytes (Figure 1).…”