A Model for FLV CR1 Isoforms Function. A) A schematic representation of heme biosynthesis is shown. Transferrin-bound iron (Tf-Fe) is taken up by cells through transferrin receptor 1 (TfR1), and iron is transferred to the mitochondrion for heme biosynthesis. It was reported that the mitochondrial iron importer MITOFERRIN1 (MFRN1) and ferrochelatase (FECH, the enzyme that catalyzes incorporation of iron into protoporphyrin IX to form heme) are part of the same complex in the inner mitochondrial membrane. FLVCR1b could work in association with this complex to allow heme export out of the mitochondrion for incorporation into new hemoproteins. Heme not used for hemoprotein synthesis is exported out of the cell through the cell-surface isoform FLVCR1a.B) During erythroid differentiation, the expression of FLVCR1b in the mitochondrion regulates heme export into the cytosol, allowing hemoglobinization of erythroid precursors. At the cell membrane, FLVCR1a regulates the export of heme in excess. The data reported by Chiabrando et al. suggest that decreased expression of the membrane heme exporter FLVCR1a and increased expression of FLVCR1b are fundamental for proper differentiation of erythroid progenitors.The Mitochondrial Heme Exporter FLVCR1b Mediates Erythroid Differentiation. Chiabrando D, Marro S, Mercurio S, et al. J Clin Invest. 2012; 122(12):4569–4579, doi:10.1172/JCI62422.