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Biliary excretion of excess iron in mice requires hepatocyte iron import by Slc39a14
Iron is essential for erythropoiesis and other biological processes, but is toxic in excess. Dietary absorption of iron is a highly regulated process and is a major determinant of body iron levels. Iron excretion, however, is considered a passive, unregulated process, and the underlying pathways are...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214222/ https://www.ncbi.nlm.nih.gov/pubmed/34051234 http://dx.doi.org/10.1016/j.jbc.2021.100835 |
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author | Prajapati, Milankumar Conboy, Heather L. Hojyo, Shintaro Fukada, Toshiyuki Budnik, Bogdan Bartnikas, Thomas B. |
author_facet | Prajapati, Milankumar Conboy, Heather L. Hojyo, Shintaro Fukada, Toshiyuki Budnik, Bogdan Bartnikas, Thomas B. |
author_sort | Prajapati, Milankumar |
collection | PubMed |
description | Iron is essential for erythropoiesis and other biological processes, but is toxic in excess. Dietary absorption of iron is a highly regulated process and is a major determinant of body iron levels. Iron excretion, however, is considered a passive, unregulated process, and the underlying pathways are unknown. Here we investigated the role of metal transporters SLC39A14 and SLC30A10 in biliary iron excretion. While SLC39A14 imports manganese into the liver and other organs under physiological conditions, it imports iron under conditions of iron excess. SLC30A10 exports manganese from hepatocytes into the bile. We hypothesized that biliary excretion of excess iron would be impaired by SLC39A14 and SLC30A10 deficiency. We therefore analyzed biliary iron excretion in Slc39a14-and Slc30a10-deficient mice raised on iron-sufficient and -rich diets. Bile was collected surgically from the mice, then analyzed with nonheme iron assays, mass spectrometry, ELISAs, and an electrophoretic assay for iron-loaded ferritin. Our results support a model in which biliary excretion of excess iron requires iron import into hepatocytes by SLC39A14, followed by iron export into the bile predominantly as ferritin, with iron export occurring independently of SLC30A10. To our knowledge, this is the first report of a molecular determinant of mammalian iron excretion and can serve as basis for future investigations into mechanisms of iron excretion and relevance to iron homeostasis. |
format | Online Article Text |
id | pubmed-8214222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-82142222021-06-29 Biliary excretion of excess iron in mice requires hepatocyte iron import by Slc39a14 Prajapati, Milankumar Conboy, Heather L. Hojyo, Shintaro Fukada, Toshiyuki Budnik, Bogdan Bartnikas, Thomas B. J Biol Chem Research Article Iron is essential for erythropoiesis and other biological processes, but is toxic in excess. Dietary absorption of iron is a highly regulated process and is a major determinant of body iron levels. Iron excretion, however, is considered a passive, unregulated process, and the underlying pathways are unknown. Here we investigated the role of metal transporters SLC39A14 and SLC30A10 in biliary iron excretion. While SLC39A14 imports manganese into the liver and other organs under physiological conditions, it imports iron under conditions of iron excess. SLC30A10 exports manganese from hepatocytes into the bile. We hypothesized that biliary excretion of excess iron would be impaired by SLC39A14 and SLC30A10 deficiency. We therefore analyzed biliary iron excretion in Slc39a14-and Slc30a10-deficient mice raised on iron-sufficient and -rich diets. Bile was collected surgically from the mice, then analyzed with nonheme iron assays, mass spectrometry, ELISAs, and an electrophoretic assay for iron-loaded ferritin. Our results support a model in which biliary excretion of excess iron requires iron import into hepatocytes by SLC39A14, followed by iron export into the bile predominantly as ferritin, with iron export occurring independently of SLC30A10. To our knowledge, this is the first report of a molecular determinant of mammalian iron excretion and can serve as basis for future investigations into mechanisms of iron excretion and relevance to iron homeostasis. American Society for Biochemistry and Molecular Biology 2021-05-26 /pmc/articles/PMC8214222/ /pubmed/34051234 http://dx.doi.org/10.1016/j.jbc.2021.100835 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Prajapati, Milankumar Conboy, Heather L. Hojyo, Shintaro Fukada, Toshiyuki Budnik, Bogdan Bartnikas, Thomas B. Biliary excretion of excess iron in mice requires hepatocyte iron import by Slc39a14 |
title | Biliary excretion of excess iron in mice requires hepatocyte iron import by Slc39a14 |
title_full | Biliary excretion of excess iron in mice requires hepatocyte iron import by Slc39a14 |
title_fullStr | Biliary excretion of excess iron in mice requires hepatocyte iron import by Slc39a14 |
title_full_unstemmed | Biliary excretion of excess iron in mice requires hepatocyte iron import by Slc39a14 |
title_short | Biliary excretion of excess iron in mice requires hepatocyte iron import by Slc39a14 |
title_sort | biliary excretion of excess iron in mice requires hepatocyte iron import by slc39a14 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214222/ https://www.ncbi.nlm.nih.gov/pubmed/34051234 http://dx.doi.org/10.1016/j.jbc.2021.100835 |
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