A paper from Emanuela Tolosano’s group described a key role for the heme exporter FLVCR1 in the regulation of the expansion and differentiation of committed erythroid progenitors.

Feline Leukemia Virus subgroup C Receptor 1 (Flvcr1) gene encodes for two heme exporters, FLVCR1a and FLVCR1b localized at the plasma and mitochondrial membrane, respectively.

In a recent paper published on Haematologica, Sonia Mercurio and collegues addressed the specific functions of Flvcr1a and Flvcr1b in erythropoiesis, the process that produces the highest amount of heme. They showed that, in mice and zebrafish, Flvcr1a is required for the expansion of committed erythroid progenitors but cannot drive their terminal differentiation, while Flvcr1b contributes to the expansion phase and it is required for differentiation. Moreover, by using FLVCR1a- or FLVCR1a/1b-down-regulated K562 cells, they established a link, on one hand, between FLVCR1a deficiency, cytosolic heme accumulation and defective proliferation, and, on the other, between FLVCR1a/1b-down-regulation, mitochondrial heme accumulation and impairment of both proliferation and differentiation.

These data support a model in which the coordinated expression of Flvcr1a and Flvcr1b contributes to control the size of the cytosolic heme pool required to sustain metabolic activity during the expansion of erythroid progenitors and to allow hemoglobin production during their terminal maturation.

The studies on Flvcr1a and Flvcr1b, not only in erythroid cells but also in other cell types like hepatocytes and intestinal cells, reveal the exquisite mechanisms in controlling heme balance within the cell. Future work is needed to elucidate how intracellular heme transport coordinates with heme synthesis and degradation to achieve optimal intracellular heme balance.