Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1973 Aug;72(2):295–336.

The relationship of intracellular pathways of iron metabolism to cellular iron overload and the iron storage diseases. Cell sap and cytocavitary network pathways in relation to lysosomal storage and turnover of iron macromolecules.

B F Trump, J M Valigorsky, A U Arstila, W J Mergner, T D Kinney
PMCID: PMC1903989  PMID: 4579280

Full text

PDF
295

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adelman M. R., Sabatini D. D., Blobel G. Ribosome-membrane interaction. Nondestructive disassembly of rat liver rough microsomes into ribosomal and membranous components. J Cell Biol. 1973 Jan;56(1):206–229. doi: 10.1083/jcb.56.1.206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ainsworth S. K., Karnovsky M. J. An ultrastructural staining method for enhancing the size and electron opacity of ferritin in thin sections. J Histochem Cytochem. 1972 Mar;20(3):225–229. doi: 10.1177/20.3.225. [DOI] [PubMed] [Google Scholar]
  3. Albahary C. Lead and hemopoiesis. The mechanism and consequences of the erythropathy of occupational lead poisoning. Am J Med. 1972 Mar;52(3):367–378. doi: 10.1016/0002-9343(72)90025-3. [DOI] [PubMed] [Google Scholar]
  4. Arstila A. U., Bradford W. D., Kinney T. D., Trump B. F. Iron metabolism and cell membranes. II. The relationship of ferritin to the cytocavitary network in rat hepatic parenchymal cells. Am J Pathol. 1970 Mar;58(3):419–450. [PMC free article] [PubMed] [Google Scholar]
  5. Arstila A. U., Jauregui H. O., Chang J., Trump B. F. Studies on cellular autophagocytosis. Relationship between heterophagy and autophagy in HeLa cells. Lab Invest. 1971 Feb;24(2):162–174. [PubMed] [Google Scholar]
  6. Arstila A. U., Jauregui H. O., Chang J., Trump B. F. Studies on cellular autophagocytosis. Relationship between heterophagy and autophagy in HeLa cells. Lab Invest. 1971 Feb;24(2):162–174. [PubMed] [Google Scholar]
  7. Arstila A. U., Smith M. A., Trump B. F. Microsomal lipid peroxidation: morphological characterization. Science. 1972 Feb 4;175(4021):530–533. doi: 10.1126/science.175.4021.530. [DOI] [PubMed] [Google Scholar]
  8. Arstila A. U., Trump B. F. Ethionine induced alterations in the Golgi apparatus and in the endoplasmic reticulum. Virchows Arch B Cell Pathol. 1972;10(4):344–353. doi: 10.1007/BF02899744. [DOI] [PubMed] [Google Scholar]
  9. Arstila A. U., Trump B. F. Studies on cellular autophagocytosis. The formation of autophagic vacuoles in the liver after glucagon administration. Am J Pathol. 1968 Nov;53(5):687–733. [PMC free article] [PubMed] [Google Scholar]
  10. BESSIS M. C., BRETON-GORIUS J. Ferrtin and ferruginous micelles in normal erythroblasts and hypochromic hypersideremic anemias. Blood. 1959 Apr;14(4):423–432. [PubMed] [Google Scholar]
  11. BESSIS M. C., BRETON-GORIUS J. Iron metabolism in the bone marrow as seen by electron microscopy: a critical review. Blood. 1962 Jun;19:635–663. [PubMed] [Google Scholar]
  12. BESSIS M. C., BRETON-GORIUS J. Iron particles in normal erythroblasts and normal and pathological erythrocytes. J Biophys Biochem Cytol. 1957 May 25;3(3):503–504. doi: 10.1083/jcb.3.3.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Bradford W. D., Elchlepp J. G., Arstila A. U., Trump B. F., Kinney T. D. Iron metabolism and cell membranes. I. Relation between ferritin and hemosiderin in bile and biliary excretion of lysosome contents. Am J Pathol. 1969 Aug;56(2):201–228. [PMC free article] [PubMed] [Google Scholar]
  14. Brown J. N., Harris J. R. The entry of ferritin into hemoglobin-free human erythrocyte ghosts prepared under different conditions. J Ultrastruct Res. 1970 Sep;32(5):405–416. doi: 10.1016/s0022-5320(70)80018-1. [DOI] [PubMed] [Google Scholar]
  15. Bruns R. R., Palade G. E. Studies on blood capillaries. II. Transport of ferritin molecules across the wall of muscle capillaries. J Cell Biol. 1968 May;37(2):277–299. doi: 10.1083/jcb.37.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bulger R. E., Trump B. F. A mechanism for rapid transport of colloidal particles by flounder renal epithelium. J Morphol. 1969 Feb;127(2):205–223. doi: 10.1002/jmor.1051270206. [DOI] [PubMed] [Google Scholar]
  17. CARO L. G., PALADE G. E. PROTEIN SYNTHESIS, STORAGE, AND DISCHARGE IN THE PANCREATIC EXOCRINE CELL. AN AUTORADIOGRAPHIC STUDY. J Cell Biol. 1964 Mar;20:473–495. doi: 10.1083/jcb.20.3.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. CONRAD M. E., Jr, CROSBY W. H. INTESTINAL MUCOSAL MECHANISMS CONTROLLING IRON ABSORPTION. Blood. 1963 Oct;22:406–415. [PubMed] [Google Scholar]
  19. CONRAD M. E., WEINTRAUB L. R., CROSBY W. H. THE ROLE OF THE INTESTINE IN IRON KINETICS. J Clin Invest. 1964 May;43:963–974. doi: 10.1172/JCI104982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Chu L. L., Fineberg R. A. On the mechanism of iron-induced synthesis of apoferritin in HeLa cells. J Biol Chem. 1969 Jul 25;244(14):3847–3854. [PubMed] [Google Scholar]
  21. Coffey J. W., De Duve C. Digestive activity of lysosomes. I. The digestion of proteins by extracts of rat liver lysosomes. J Biol Chem. 1968 Jun 25;243(12):3255–3263. [PubMed] [Google Scholar]
  22. Cohn Z. A., Fedorko M. E., Hirsch J. G. The in vitro differentiation of mononuclear phagocytes. V. The formation of macrophage lysosomes. J Exp Med. 1966 Apr 1;123(4):757–766. doi: 10.1084/jem.123.4.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Crichton R. R. Ferritin: structure, synthesis and function. N Engl J Med. 1971 Jun 24;284(25):1413–1422. doi: 10.1056/NEJM197106242842506. [DOI] [PubMed] [Google Scholar]
  24. DOWDLE E. B., SCHACHTER D., SCHENKER H. Active transport of Fe59 by everted segments of rat duodenum. Am J Physiol. 1960 Mar;198:609–613. doi: 10.1152/ajplegacy.1960.198.3.609. [DOI] [PubMed] [Google Scholar]
  25. DRYSDALE J. W., MUNRO H. N. FAILURE OF ACTINOMYCIN D TO PREVENT INDUCTION OF LIVER APOFERRITIN AFTER IRON ADMINISTRATION. Biochim Biophys Acta. 1965 May 11;103:185–188. doi: 10.1016/0005-2787(65)90554-x. [DOI] [PubMed] [Google Scholar]
  26. Deiss A., Cartwright G. E. Ferritin metabolism in reticulated-siderocytes. J Clin Invest. 1970 Mar;49(3):517–523. doi: 10.1172/JCI106261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Drysdale J. W., Munro H. N. Regulation of synthesis and turnover of ferritin in rat liver. J Biol Chem. 1966 Aug 10;241(15):3630–3637. [PubMed] [Google Scholar]
  28. Easterbrook K. B. The arrangement of subunits in the shell of ferritin. Electron microscopic observations of molecules negatively stained with uranyl acetate. J Ultrastruct Res. 1970 Dec;33(5):442–450. doi: 10.1016/s0022-5320(70)90173-5. [DOI] [PubMed] [Google Scholar]
  29. FELDHERR C. M. The intracellular distribution of ferritin following microinjection. J Cell Biol. 1962 Jan;12:159–167. doi: 10.1083/jcb.12.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Fischbach F. A., Gregory D. W., Harrison P. M., Hoy T. G., Williams J. M. On the structure of hemosiderin and its relationship to ferritin. J Ultrastruct Res. 1971 Dec;37(5):495–503. doi: 10.1016/s0022-5320(71)80020-5. [DOI] [PubMed] [Google Scholar]
  31. Franke W. W., Kartenbeck J. Outer mitochondrial membrane continuous with endoplasmic reticulum. Protoplasma. 1971;73(1):35–41. doi: 10.1007/BF01286409. [DOI] [PubMed] [Google Scholar]
  32. GOLBERG L., SMITH J. P. Iron overloading and hepatic vulnerability. Am J Pathol. 1960 Feb;36:125–149. [PMC free article] [PubMed] [Google Scholar]
  33. Graney D. O. The uptake of ferritin by ileal absorptive cells in suckling rats. An electron microscope study. Am J Anat. 1968 Sep;123(2):227–254. doi: 10.1002/aja.1001230202. [DOI] [PubMed] [Google Scholar]
  34. HARRISON P. M. The structure of apoferritin: molecular size, shape and symmetry from x-ray data. J Mol Biol. 1963 May;6:404–422. doi: 10.1016/s0022-2836(63)80052-2. [DOI] [PubMed] [Google Scholar]
  35. HUNTER F. E., Jr, GEBICKI J. M., HOFFSTEN P. E., WEINSTEIN J., SCOTT A. Swelling and lysis of rat liver mitochondria induced by ferrous ions. J Biol Chem. 1963 Feb;238:828–835. [PubMed] [Google Scholar]
  36. Haggis G. H. The iron oxide core of the ferritin molecule. J Mol Biol. 1965 Dec;14(2):598–602. doi: 10.1016/s0022-2836(65)80210-8. [DOI] [PubMed] [Google Scholar]
  37. Han S. S., Han I. H., Johnson A. G. The fate of isologous, homologous and heterologous ferritin molecules in the rat. Am J Anat. 1970 Oct;129(2):141–167. doi: 10.1002/aja.1001290203. [DOI] [PubMed] [Google Scholar]
  38. Harrison P. M., Fischbach F. A., Hoy T. G., Haggis G. H. Ferric oxyhydroxide core of ferritin. Nature. 1967 Dec 23;216(5121):1188–1190. doi: 10.1038/2161188a0. [DOI] [PubMed] [Google Scholar]
  39. Hashimoto K., Brownstein M. H. Amyloidogenesis in healing wound. Electron microscopic studies of biopsied wounds in macular amyloidosis. Am J Pathol. 1972 Aug;68(2):371–390. [PMC free article] [PubMed] [Google Scholar]
  40. Haydon G. B. Visualization of substructure in ferritin molecules: an artifact. J Microsc. 1969;89(2):251–261. doi: 10.1111/j.1365-2818.1969.tb00672.x. [DOI] [PubMed] [Google Scholar]
  41. Jamieson J. D., Palade G. E. Intracellular transport of secretory proteins in the pancreatic exocrine cell. I. Role of the peripheral elements of the Golgi complex. J Cell Biol. 1967 Aug;34(2):577–596. doi: 10.1083/jcb.34.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. KENT G., MINICK O. T., VOLINI F. I., ORFEI E., DELAHUERGA J. IRON STORAGE IN N-2-FLUORENYLACETAMIDE-INDUCED HEPATIC INJURY. ELECTRON MICROSCOPIC OBSERVATIONS FOLLOWING THE INJECTION OF IRON-DEXTRAN. Lab Invest. 1963 Nov;12:1102–1112. [PubMed] [Google Scholar]
  43. KENT G., VOLINI F. I., ORFEI E., MINICK O. T., DELAHUERGA J. EFFECT OF HEPATIC INJURIES UPON IRON STORAGE IN THE LIVER. Lab Invest. 1963 Nov;12:1094–1101. [PubMed] [Google Scholar]
  44. Linder M. C., Munro H. N. Metabolic and chemical features of ferritins, a series of iron-inducible tissue proteins. Am J Pathol. 1973 Aug;72(2):263–282. [PMC free article] [PubMed] [Google Scholar]
  45. MATIOLI G. T., BAKER R. F. Denaturation of ferritin and its relationship with hemosiderin. J Ultrastruct Res. 1963 Jun;8:477–490. doi: 10.1016/s0022-5320(63)80050-7. [DOI] [PubMed] [Google Scholar]
  46. Macara I. G., Hoy T. G., Harrison P. M. The formation of ferritin from apoferritin. Kinetics and mechanism of iron uptake. Biochem J. 1972 Jan;126(1):151–162. doi: 10.1042/bj1260151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Maunsbach A. B. Absorption of ferritin by rat kidney proximal tubule cells. Electron microscopic observations of the initial uptake phase in cells of microperfused single proximal tubules. J Ultrastruct Res. 1966 Sep;16(1):1–12. doi: 10.1016/s0022-5320(66)80019-9. [DOI] [PubMed] [Google Scholar]
  48. Millar J. A., Cumming R. L., Smith J. A., Goldberg A. Effect of actinomycin D, cycloheximide, and acute blood loss of ferritin synthesis in rat liver. Biochem J. 1970 Oct;119(4):643–649. doi: 10.1042/bj1190643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Miller J. P., Perkins D. J. Model experiments for the study of iron transfer from transferrin to ferritin. Eur J Biochem. 1969 Aug;10(1):146–151. doi: 10.1111/j.1432-1033.1969.tb00666.x. [DOI] [PubMed] [Google Scholar]
  50. Munro H. N., Drysdale J. W. Role of iron in the regulation of ferritin metabolism. Fed Proc. 1970 Jul-Aug;29(4):1469–1473. [PubMed] [Google Scholar]
  51. NOVIKOFF A. B., ESSNER E., QUINTANA N. GOLGI APPARATUS AND LYSOSOMES. Fed Proc. 1964 Sep-Oct;23:1010–1022. [PubMed] [Google Scholar]
  52. Puro D. G., Richter G. W. Ferritin synthesis by free and membrane-bound (poly)ribosomes of rat liver. Proc Soc Exp Biol Med. 1971 Nov;138(2):399–403. doi: 10.3181/00379727-138-35906. [DOI] [PubMed] [Google Scholar]
  53. RICHTER G. W. A study of hemosiderosis with the aid of electron microscopy; with observations on the relationship between hemosiderin and ferritin. J Exp Med. 1957 Aug 1;106(2):203–218. doi: 10.1084/jem.106.2.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. RICHTER G. W. Activation of ferritin synthesis and induction of changes in fine structure in HeLa cells in vitro: implications for protein synthesis. Nature. 1961 Apr 29;190:413–415. doi: 10.1038/190413a0. [DOI] [PubMed] [Google Scholar]
  55. RICHTER G. W. ON FERRITIN AND ITS PRODUCTION BY CELLS GROWING. Lab Invest. 1963 Oct;12:1026–1039. [PubMed] [Google Scholar]
  56. RICHTER G. W. The cellular transformation of injected colloidal iron complexes into ferritin and hemosiderin in experimental animals; a study with the aid of electron microscopy. J Exp Med. 1959 Feb 1;109(2):197–216. doi: 10.1084/jem.109.2.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Redman C. M. Biosynthesis of serum proteins and ferritin by free and attached ribosomes of rat liver. J Biol Chem. 1969 Aug 25;244(16):4308–4315. [PubMed] [Google Scholar]
  58. Richter G. W. Immunologic properties of ferritin. Am J Pathol. 1973 Aug;72(2):283–294. [PMC free article] [PubMed] [Google Scholar]
  59. Smith L., Fineberg R. A. Serum requirement for apoferritin induction in rat liver slices. Blood. 1972 Feb;39(2):274–283. [PubMed] [Google Scholar]
  60. Svoboda D., Grady H., Azarnoff D. Microbodies in experimentally altered cells. J Cell Biol. 1967 Oct;35(1):127–152. doi: 10.1083/jcb.35.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Tanaka Y., Cushard J. A. Crystalloid array of ferritin particles on the plasma membrane of guinea pig erythroblasts. J Ultrastruct Res. 1970 Dec;33(5):436–441. doi: 10.1016/s0022-5320(70)90172-3. [DOI] [PubMed] [Google Scholar]
  62. Witzleben C. L. An electron microscopic study of ferrous sulfate induced liver damage. Am J Pathol. 1966 Dec;49(6):1053–1067. [PMC free article] [PubMed] [Google Scholar]
  63. Witzleben C. L., Buck B. E. Iron overload hepatotoxicity: a postulated pathogenesis. Clin Toxicol. 1971 Dec;4(4):579–583. doi: 10.3109/15563657108990980. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES