Mammalian SLC39A13 promotes ER/Golgi iron transport and iron homeostasis in multiple compartments
Abstract Iron is a potent biochemical, and accurate homeostatic control is orchestrated by a network of interacting players at multiple levels. Although our understanding of organismal iron homeostasis has advanced, intracellular iron homeostasis is poorly understood, including coordination between...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55149-2 |
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| author | Huihui Li Yanmei Cui Yule Hu Mengran Zhao Kuanyu Li Xiaoyun Pang Fei Sun Bing Zhou |
| author_facet | Huihui Li Yanmei Cui Yule Hu Mengran Zhao Kuanyu Li Xiaoyun Pang Fei Sun Bing Zhou |
| author_sort | Huihui Li |
| collection | DOAJ |
| description | Abstract Iron is a potent biochemical, and accurate homeostatic control is orchestrated by a network of interacting players at multiple levels. Although our understanding of organismal iron homeostasis has advanced, intracellular iron homeostasis is poorly understood, including coordination between organelles and iron export into the ER/Golgi. Here, we show that SLC39A13 (ZIP13), previously identified as a zinc transporter, promotes intracellular iron transport and reduces intracellular iron levels. ZIP13 loss causes an iron deficiency in the ER/Golgi and other intracellular compartments, such as lysosomes and mitochondria, as well as elevating iron in the cytosol. ZIP13 overexpression has the opposite effect, increasing iron in organellar compartments. We suggest that ZIP13 gatekeeps an iron trafficking route that shunts iron from the cytosol to the ER/Golgi hub. Zip13-knockout male mice have iron deposition in several tissues. These data demonstrate that mammalian ZIP13 is crucial for iron homeostasis and suggest a potential iron transport function. |
| format | Article |
| id | doaj-art-921afb946108463db6eb2b5473f5f7b4 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-921afb946108463db6eb2b5473f5f7b42025-01-05T12:34:38ZengNature PortfolioNature Communications2041-17232024-12-0115111310.1038/s41467-024-55149-2Mammalian SLC39A13 promotes ER/Golgi iron transport and iron homeostasis in multiple compartmentsHuihui Li0Yanmei Cui1Yule Hu2Mengran Zhao3Kuanyu Li4Xiaoyun Pang5Fei Sun6Bing Zhou7Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesShenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesShenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesBeijing Key Laboratory for Precancerous Lesion of Digestive Disease, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical UniversityJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing UniversityNational Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesShenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesAbstract Iron is a potent biochemical, and accurate homeostatic control is orchestrated by a network of interacting players at multiple levels. Although our understanding of organismal iron homeostasis has advanced, intracellular iron homeostasis is poorly understood, including coordination between organelles and iron export into the ER/Golgi. Here, we show that SLC39A13 (ZIP13), previously identified as a zinc transporter, promotes intracellular iron transport and reduces intracellular iron levels. ZIP13 loss causes an iron deficiency in the ER/Golgi and other intracellular compartments, such as lysosomes and mitochondria, as well as elevating iron in the cytosol. ZIP13 overexpression has the opposite effect, increasing iron in organellar compartments. We suggest that ZIP13 gatekeeps an iron trafficking route that shunts iron from the cytosol to the ER/Golgi hub. Zip13-knockout male mice have iron deposition in several tissues. These data demonstrate that mammalian ZIP13 is crucial for iron homeostasis and suggest a potential iron transport function.https://doi.org/10.1038/s41467-024-55149-2 |
| spellingShingle | Huihui Li Yanmei Cui Yule Hu Mengran Zhao Kuanyu Li Xiaoyun Pang Fei Sun Bing Zhou Mammalian SLC39A13 promotes ER/Golgi iron transport and iron homeostasis in multiple compartments Nature Communications |
| title | Mammalian SLC39A13 promotes ER/Golgi iron transport and iron homeostasis in multiple compartments |
| title_full | Mammalian SLC39A13 promotes ER/Golgi iron transport and iron homeostasis in multiple compartments |
| title_fullStr | Mammalian SLC39A13 promotes ER/Golgi iron transport and iron homeostasis in multiple compartments |
| title_full_unstemmed | Mammalian SLC39A13 promotes ER/Golgi iron transport and iron homeostasis in multiple compartments |
| title_short | Mammalian SLC39A13 promotes ER/Golgi iron transport and iron homeostasis in multiple compartments |
| title_sort | mammalian slc39a13 promotes er golgi iron transport and iron homeostasis in multiple compartments |
| url | https://doi.org/10.1038/s41467-024-55149-2 |
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