Hrg1 promotes heme-iron recycling during hemolysis in the zebrafish kidney

作者：Jianbing Zhang, Ian G. Chambers, Sijung Yun, John D. Phillips, Michael Krause, Iqbal Hamza · 发表于：PLoS Genetics · 年份：2018 · DOI：10.1371/journal.pgen.1007665 · 被引用次数：30 · 研究领域：Iron Metabolism and Disorders、Hemoglobinopathies and Related Disorders、Erythrocyte Function and Pathophysiology

Heme-iron recycling from senescent red blood cells (erythrophagocytosis) accounts for the majority of total body iron in humans. Studies in cultured cells have ascribed a role for HRG1/SLC48A1 in heme-iron transport but the in vivo function of this heme transporter is unclear. Here we present genetic evidence in a zebrafish model that Hrg1 is essential for macrophage-mediated heme-iron recycling during erythrophagocytosis in the kidney. Furthermore, we show that zebrafish Hrg1a and its paralog Hrg1b are functional heme transporters, and genetic ablation of both transporters in double knockout (DKO) animals shows lower iron accumulation concomitant with higher amounts of heme sequestered in kidney macrophages. RNA-seq analyses of DKO kidney revealed large-scale perturbation in genes related to heme, iron metabolism and immune functions. Taken together, our results establish the kidney as the major organ for erythrophagocytosis and identify Hrg1 as an important regulator of heme-iron recycling by macrophages in the adult zebrafish.