SLC39A14 Is Required for the Development of Hepatocellular Iron Overload in Murine Models of Hereditary Hemochromatosis

Supak Jenkitkasemwong, Chia Yu Wang, Richard Coffey, Wei Zhang, Alan Chan, Thomas Biel, Jae Sung Kim, Shintaro Hojyo, Toshiyuki Fukada, Mitchell D. Knutson

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Summary Nearly all forms of hereditary hemochromatosis are characterized by pathological iron accumulation in the liver, pancreas, and heart. These tissues preferentially load iron because they take up non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. Yet, how tissues take up NTBI is largely unknown. We report that ablation of Slc39a14, the gene coding for solute carrier SLC39A14 (also called ZIP14), in mice markedly reduced the uptake of plasma NTBI by the liver and pancreas. To test the role of SLC39A14 in tissue iron loading, we crossed Slc39a14-/- mice with Hfe-/- and Hfe2-/- mice, animal models of type 1 and type 2 (juvenile) hemochromatosis, respectively. Slc39a14 deficiency in hemochromatotic mice greatly diminished iron loading of the liver and prevented iron deposition in hepatocytes and pancreatic acinar cells. The data suggest that inhibition of SLC39A14 may mitigate hepatic and pancreatic iron loading and associated pathologies in iron overload disorders.

Original languageEnglish
Pages (from-to)138-150
Number of pages13
JournalCell metabolism
Volume22
Issue number1
DOIs
StatePublished - Jul 7 2015

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