Normal Iron Homeostasis Requires the Transporter SLC48A1 for Efficient Heme-Iron Recycling in Mammals.
Normal Iron Homeostasis Requires the Transporter SLC48A1 for Efficient Heme-Iron Recycling in Mammals.
复制标题
DOI：
10.3389/fgeed.2020.00008
复制
发表时间：
2020
影响因子：
--
通讯作者：
Bodine DM
中科院分区：
文献类型：
--
作者：
Simmons WR;Wain L;Toker J;Jagadeesh J;Garrett LJ;Pek RH;Hamza I;Bodine DM
哺乳动物体内超过65%的铁位于血红蛋白血红素部分的红细胞中。铁稳态需要肠道从饮食中吸收铁，并在破坏衰老红细胞后再循环铁。衰老的红细胞被网状内皮系统巨噬细胞吞噬，其中血红蛋白在溶酶体中被分解，释放血红素用于细胞质中的铁恢复。我们最近发现SLC48A1蛋白负责将血红素从溶酶体转运到细胞质。CRISPR生成的slc48a1缺陷小鼠在网状内皮系统巨噬细胞中以血色素晶体的形式积累血红素。在这里，我们描述了slc48a1缺陷小鼠的其他特征。我们发现，在8日龄slc48a1缺陷小鼠的网状内皮系统巨噬细胞中首先出现可见的血色素，表明红细胞循环开始。对摄入铁控制饮食的正常和slc48a1缺陷小鼠的评估表明，slc48a1介导的铁循环至少相当于百万分之十的膳食铁。我们提出人类SLC48A1突变可能导致特发性铁失调。
In mammals over 65% of the total body iron is located within erythrocytes in the heme moieties of hemoglobin. Iron homeostasis requires iron absorbed from the diet by the gut as well as recycling of iron after the destruction of senescent erythrocytes. Senescent erythrocytes are engulfed by reticuloendothelial system macrophages where hemoglobin is broken down in the lysosomes, releasing heme for iron recovery in the cytoplasm. We recently showed that the SLC48A1 protein is responsible for transporting heme from the lysosome to the cytoplasm. CRISPR generated SLC48A1-deficient mice accumulate heme in their reticuloendothelial system macrophages as hemozoin crystals. Here we describe additional features of SLC48A1-deficient mice. We show that visible hemozoin first appears in the reticuloendothelial system macrophages of SLC48A1-deficient mice at 8 days of age, indicating the onset of erythrocyte recycling. Evaluation of normal and SLC48A1-deficient mice on iron-controlled diets show that SLC48A1-mediated iron recycling is equivalent to at least 10 parts per million of dietary iron. We propose that mutations in human SLC48A1 could contribute to idiopathic iron disorders.
登录
查看更多内容
影响因子：
3.2
作者：
Chung J;Chen C;Paw BH
通讯作者：
Paw BH
影响因子：
3
作者：
Marciano, Ortal;Moskovitz, Yoni;Ruthstein, Sharon
通讯作者：
Ruthstein, Sharon
影响因子：
7.7
作者：
Pek, Rini H.;Yuan, Xiaojing;Hamza, Iqbal
通讯作者：
Hamza, Iqbal
影响因子：
--
作者：
Giger KM;Kalfa TA
通讯作者：
Kalfa TA
影响因子：
29
作者：
Korolnek T;Zhang J;Beardsley S;Scheffer GL;Hamza I
通讯作者：
Hamza I