Biological and ultrastructural aspects of iron overload: an overview

The morphologic aspects of iron overload have been studied in human subjects, mammals, and birds with spontaneous overload, in a variety of experimental animals, and also in cell cultures. Reviewed here are the contributions of electron microscopy to the understanding of the iron-loading process, as reported during the last 12 years. The electron-density of ferrihydrite cores located within the protein shell of the ferritin molecule enabled its identification within either cytosol or lysosomes (siderosomes) of iron-exposed cells. The process of (holo)ferritin assembly, its transfer into siderosomes, and its degradation to hemosiderin can be followed in various cells. Siderosomes display cell-line-specific ultrastructural features, and different cell types show varying iron-segregating capacity. The study of experimental animals and cultured cells show that an iron-rich milieu may be damaging, probably through iron-catalyzed lipid peroxidation. Recent ultrastructural studies stress the value of describing initial alterations as opposed to the irrelevant end-stage findings. Further efforts should be directed toward elucidating the origin of iron in neonatal hemochromatosis, the role of iron in infection and neoplasia, and the nature and role of brain iron.