American Society of Hematology

Fig. 8.

$Fig. 8. Model for iron uptake and transport in transformed versus normal erythroblasts. / In committed primary erythroblasts (SCF cells), after endocytosis, a large proportion of the highly abundant iron-loaded Tf/TfR complexes resides in undissociated form in the endosomal compartment due to its relatively high pH. The fraction of ferrous iron leaving the endosomes via the action of DMT154-57 is directly shunted into mitochondria, where most of it is incorporated into heme and iron-sulfur clusters. Only minor amounts of iron-containing compounds are released into the cytosol through the action of iron transporters (candidate genes possibly involved are the ATB-binding cassette (ABC) transporter ABC7606667 or the erythroid-specific ABC-me protein 968) and registered by the IRP sensory system. Although transformed erythroleukemic cells (like HD3) express less TfR, their more acidic endosomes favor an enhanced flow of iron through the mitochondria (in the absence of heme synthesis). In consequence, on iron overload, IRP harbors the complete 4Fe-4S cluster, leading to the conformation that does not bind IRE elements, thus further reducing TfR expression. See “Discussion” for further details and references.$

Model for iron uptake and transport in transformed versus normal erythroblasts.

In committed primary erythroblasts (SCF cells), after endocytosis, a large proportion of the highly abundant iron-loaded Tf/TfR complexes resides in undissociated form in the endosomal compartment due to its relatively high pH. The fraction of ferrous iron leaving the endosomes via the action of DMT154-57 is directly shunted into mitochondria, where most of it is incorporated into heme and iron-sulfur clusters. Only minor amounts of iron-containing compounds are released into the cytosol through the action of iron transporters (candidate genes possibly involved are the ATB-binding cassette (ABC) transporter ABC760,66,67 or the erythroid-specific ABC-me protein 968) and registered by the IRP sensory system. Although transformed erythroleukemic cells (like HD3) express less TfR, their more acidic endosomes favor an enhanced flow of iron through the mitochondria (in the absence of heme synthesis). In consequence, on iron overload, IRP harbors the complete 4Fe-4S cluster, leading to the conformation that does not bind IRE elements, thus further reducing TfR expression. See “Discussion” for further details and references.

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