HRG1 Is Essential for Heme Transport from the Phagolysosome of Macrophages during Erythrophagocytosis

被引：194

作者：

White, Carine ^{[1
,2
]}

Yuan, Xiaojing ^{[1
,2
]}

Schmidt, Paul J. ^{[3
]}

Bresciani, Erica ^{[4
]}

Samuel, Tamika K. ^{[1
,2
]}

Campagna, Dean ^{[3
]}

Hall, Caitlin ^{[1
,2
]}

Bishop, Kevin ^{[5
]}

Calicchio, Monica L. ^{[3
]}

Lapierre, Ariane ^{[3
]}

Ward, Diane M. ^{[6
]}

Liu, Paul ^{[4
]}

Fleming, Mark D. ^{[3
]}

Hamza, Iqbal ^{[1
,2
]}

机构：

[1] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA

[2] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA

[3] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA

[4] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA

[5] NHGRI, Zebrafish Core, NIH, Bethesda, MD 20892 USA

[6] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84132 USA

来源：

CELL METABOLISM | 2013年 / 17卷 / 02期

基金：

美国国家卫生研究院;

关键词：

IRON-OVERLOAD; OXYGENASE; SYSTEM; MICE; IDENTIFICATION; ANEMIA; BACH1; HEMOCHROMATOSIS; MECHANISMS; RESISTANCE;

D O I：

10.1016/j.cmet.2013.01.005

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Adult humans have about 25 trillion red blood cells (RBCs), and each second we recycle about 5 million RBCs by erythrophagocytosis (EP) in macrophages of the reticuloendothelial system. Despite the central role for EP in mammalian iron metabolism, the molecules and pathways responsible for heme trafficking during EP remain unknown. Here, we show that the mammalian homolog of HRG1, a transmembrane heme permease in C. elegans, is essential for macrophage iron homeostasis and transports heme from the phagolysosome to the cytoplasm during EP. HRG1 is strongly expressed in macrophages of the reticuloendothelial system and specifically localizes to the phagolysosomal membranes during EP. Depletion of Hrg1 in mouse macrophages causes attenuation of heme transport from the phagolysosomal compartment. Importantly, missense polymorphisms in human HRG1 are defective in heme transport. Our results reveal HRG1 as the long-sought heme transporter for heme-iron recycling in macrophages and suggest that genetic variations in HRG1 could be modifiers of human iron metabolism.

引用

页码：261 / 270

页数：10

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