Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesis
Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesis
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DOI：
10.1182/blood-2009-12-259614
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发表时间：
2010-07-29
期刊：
影响因子：
20.3
通讯作者：
Paw, Barry H.
中科院分区：
文献类型：
--
作者：
Chen, Wen;Dailey, Harry A.;Paw, Barry H.
在红系细胞中，亚铁通过线粒体铁蛋白-1（Mfrn 1）进入线粒体。以前，我们发现Mfrn 1与Abcb 10相互作用，以增强线粒体铁输入。在此，我们已经获得了稳定的Friend小鼠红白血病（MEL）细胞克隆表达Mfrn 1-FLAG或Abcb 10-FLAG，并通过亲和纯化和质谱鉴定亚铁螯合酶（Fech）作为Mfrn 1和Abcb 10的相互作用蛋白。Fech是血红素合成的末端酶，催化输入的铁插入原卟啉IX中生成血红素。Mfrn 1-Fech和Abcb 10-Fech相互作用通过MEL细胞中的内源蛋白和HEK 293细胞中表达的异源蛋白的免疫沉淀/Western印迹分析来证实。此外，在MEL细胞红系分化过程中，Fech蛋白与Mfrn 1和Abcb 10平行诱导。我们的研究结果表明，费希形成一个低聚物与Mfrn 1和Abcb 10协同整合线粒体铁输入和血红素生物合成的使用。（血。2010; 116（4）：628-630）
In erythroid cells, ferrous iron is imported into the mitochondrion by mitoferrin-1 (Mfrn1). Previously, we showed that Mfrn1 interacts with Abcb10 to enhance mitochondrial iron importation. Herein we have derived stable Friend mouse erythroleukemia (MEL) cell clones expressing either Mfrn1-FLAG or Abcb10-FLAG and by affinity purification and mass spectrometry have identified ferrochelatase (Fech) as an interacting protein for both Mfrn1 and Abcb10. Fech is the terminal heme synthesis enzyme to catalyze the insertion of the imported iron into protoporphyrin IX to produce heme. The Mfrn1-Fech and Abcb10-Fech interactions were confirmed by immunoprecipitation/Western blot analysis with endogenous proteins in MEL cells and heterologous proteins expressed in HEK293 cells. Moreover, Fech protein is induced in parallel with Mfrn1 and Abcb10 during MEL cell erythroid differentiation. Our findings imply that Fech forms an oligomeric complex with Mfrn1 and Abcb10 to synergistically integrate mitochondrial iron importation and use for heme biosynthesis. (Blood. 2010; 116(4): 628-630)