FIG 13.

Model of iron acquisition, trafficking, and utilization in XLSA clone cells. Shown is a schematic representation of the iron pathway and iron use in wild-type (left) and ALAS2-mutated (right) erythroblasts. In ring sideroblasts, iron uptake was increased by the increased expression of ZIP8 and DMT1 as a compensatory mechanism against impaired heme biosynthesis. Increased amounts of intracellular iron might be transported into mitochondria by increased expression of the mitochondrial iron transporter, MFRN1. Mitochondrial iron, which could not be utilized as a heme due to low ALAS2 expression, was aberrantly deposited in the mitochondria.