Studies on the Concentration and Intracellular Localization of Iron Proteins in Liver Biopsy Specimens from Patients with Iron Overload with Special Reference to their Role in Lysosomal Disruption

  • Selden C
  • Owen M
  • Hopkins J
 et al. 
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Liver biopsies were collected from control subjects and patients with iron overload due to either primary or secondary haemochromatosis. They were analysed for iron proteins by cation exchange chromatography and flameless atomic absorption spectrophotometry. In control tissue the transferrin fraction contains 25%, ferritin 50% and haemprotein and haemosiderin 10--15% each, of the total iron. In iron overloaded tissue the ferritin and haemosiderin iron increases approximately 10- and 100-fold, respectively, compared with control tissue. There was a close positive correlation between enhanced lysosomal fragility as determined by measurements of latent N-acetyl-beta-glucosaminidase and haemosiderin content of the tissue; it is suggested that the haemosiderin is responsible for the lysosomal disruption and hence the tissue damage in iron overload. Studies were performed on the intracellular localization of ferritin and of total iron in biopsy extracts from control subjects and from patients with iron overload. In control tissue, ferritin contains most of the iron and is apparently free in the cytosol. In iron overload, ferritin is the major iron protein in the post-nuclear supernatant sedimenting into the gradient as the free protein. There are, however, significant amounts of immunoreactive ferritin deeper in the gradients but this cannot be assigned to any particular subcellular organelle. The extreme fragility of lysosomes in iron overloaded human tissue makes isolation of these organelles for detailed biochemical analysis extremely difficult.

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  • Clare Selden

  • Marie Owen

  • J. M.P. Hopkins

  • T. J. Peters

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