Li Huihui, Cui Yanmei, Hu Yule, Zhao Mengran, Li Kuanyu, Pang Xiaoyun, Sun Fei, Zhou Bing
Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Nat Commun. 2024 Dec 30;15(1):10838. doi: 10.1038/s41467-024-55149-2.
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.
铁是一种强效生物化学物质，精确的体内平衡控制由多个层面相互作用的参与者网络精心编排。尽管我们对机体铁稳态的理解已有进展，但细胞内铁稳态却知之甚少，包括细胞器之间的协调以及铁向内质网/高尔基体的输出。在此，我们表明，先前被鉴定为锌转运蛋白的SLC39A13（ZIP13）可促进细胞内铁转运并降低细胞内铁水平。ZIP13缺失会导致内质网/高尔基体以及其他细胞内区室（如溶酶体和线粒体）出现缺铁现象，同时还会使胞质中铁含量升高。ZIP13过表达则具有相反的效果，增加细胞器区室中的铁含量。我们认为，ZIP13把守着一条铁运输途径，该途径将铁从胞质分流至内质网/高尔基体中心。Zip13基因敲除的雄性小鼠在多个组织中出现铁沉积。这些数据表明，哺乳动物的ZIP13对铁稳态至关重要，并提示其具有潜在的铁运输功能。
