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. 1986 May 1;235(3):671–675. doi: 10.1042/bj2350671

Lysosomes, but not mitochondria, accumulate iron and porphyrins in porphyria induced by hexachlorobenzene.

A Tangerås
PMCID: PMC1146740  PMID: 3753436

Abstract

In female rats with porphyria induced by hexachlorobenzene, the amounts of non-haem iron and porphyrins in liver mitochondrial fractions were increased almost 3-fold and greater than 500-fold respectively compared with that of untreated animals. A considerable fraction of both iron and porphyrins in this fraction was shown to be located in lysosomes. Thus mitochondrial preparations, which were further depleted of lysosomes by Percoll-density-gradient centrifugation, contained 2.78 +/- 0.75 and 2.99 +/- 0.49 nmol of non-haem iron/mg of protein when isolated from the liver of control rats and hexachlorobenzene-treated rats respectively. Mitochondria isolated from the liver of hexachlorobenzene-treated animals contained a pool of iron (about 1 nmol/mg of protein) that was available for haem synthesis in vitro. This pool is similar to that previously reported for mitochondria isolated from the liver of rats with normal haem synthesis. Hexachlorobenzene treatment, therefore, does not affect the iron status of the mitochondria.

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Selected References

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  1. Alleman M. A., Koster J. F., Wilson J. H., Edixhoven-Bosdijk A., Slee R. G., Kroos M. J., von Eijk H. G. The involvement of iron and lipid peroxidation in the pathogenesis of HCB induced porphyria. Biochem Pharmacol. 1985 Jan 15;34(2):161–166. doi: 10.1016/0006-2952(85)90118-2. [DOI] [PubMed] [Google Scholar]
  2. Beinert H. Micro methods for the quantitative determination of iron and copper in biological material. Methods Enzymol. 1978;54:435–445. doi: 10.1016/s0076-6879(78)54027-5. [DOI] [PubMed] [Google Scholar]
  3. Borová J., Ponka P., Neuwirt J. Study of intracellular iron distribution in rabbit reticulocytes with normal and inhibited heme synthesis. Biochim Biophys Acta. 1973 Aug 17;320(1):143–156. doi: 10.1016/0304-4165(73)90174-8. [DOI] [PubMed] [Google Scholar]
  4. Bottomley S. S. Porphyrin and iron metabolism in sideroblastic anemia,. Semin Hematol. 1977 Apr;14(2):169–185. [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  6. Cohen H. J., Betcher-Lange S., Kessler D. L., Rajagopalan K. V. Hepatic sulfite oxidase. Congruency in mitochondria of prosthetic groups and activity. J Biol Chem. 1972 Dec 10;247(23):7759–7766. [PubMed] [Google Scholar]
  7. De Matteis F., Stonard M. Experimental porphyrias as models for human hepatic porphyrias. Semin Hematol. 1977 Apr;14(2):187–192. [PubMed] [Google Scholar]
  8. Granick S., Beale S. I. Hemes, chlorophylls, and related compounds: biosynthesis and metabolic regulation. Adv Enzymol Relat Areas Mol Biol. 1978;46:33–203. doi: 10.1002/9780470122914.ch2. [DOI] [PubMed] [Google Scholar]
  9. Hanstein W. G., Heitmann T. D., Sandy A., Biesterfeldt H. L., Liem H. H., Muller-Eberhard U. Effects of hexachlorobenzene and iron loading on rat liver mitochondria. Biochim Biophys Acta. 1981 Dec 18;678(3):293–299. doi: 10.1016/0304-4165(81)90106-9. [DOI] [PubMed] [Google Scholar]
  10. Harbin B. M., Dailey H. A. Orientation of ferrochelatase in bovine liver mitochondria. Biochemistry. 1985 Jan 15;24(2):366–370. doi: 10.1021/bi00323a019. [DOI] [PubMed] [Google Scholar]
  11. Hultcrantz R., Ahlberg J., Glaumann H. Isolation of two lysosomal populations from iron-overloaded rat liver with different iron concentration and proteolytic activity. Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;47(1):55–65. doi: 10.1007/BF02890189. [DOI] [PubMed] [Google Scholar]
  12. Jones M. S., Jones O. T. The structural organization of haem synthesis in rat liver mitochondria. Biochem J. 1969 Jul;113(3):507–514. doi: 10.1042/bj1130507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Masini A., Ceccarelli-Stanzani D., Tomasi A., Trenti T., Ventura E. The role of pentachlorophenol in causing mitochondrial derangement in hexachlorobenzene induced experimental porphyria. Biochem Pharmacol. 1985 Apr 15;34(8):1171–1174. doi: 10.1016/0006-2952(85)90491-5. [DOI] [PubMed] [Google Scholar]
  14. Masini A., Ceccarelli-Stanzani D., Trenti T., Rocchi E., Ventura E. Structural and functional properties of rat liver mitochondria in hexachlorobenzene induced experimental porphyria. Biochem Biophys Res Commun. 1984 Jan 13;118(1):356–363. doi: 10.1016/0006-291x(84)91109-4. [DOI] [PubMed] [Google Scholar]
  15. Masini A., Ceccarelli-Stanzani D., Trenti T., Ventura E. Transmembrane potential of liver mitochondria from hexachlorobenzene-and iron-treated rats. Biochim Biophys Acta. 1984 Nov 28;802(2):253–258. doi: 10.1016/0304-4165(84)90169-7. [DOI] [PubMed] [Google Scholar]
  16. Neat C. E., Thomassen M. S., Osmundsen H. Induction of peroxisomal beta-oxidation in rat liver by high-fat diets. Biochem J. 1980 Jan 15;186(1):369–371. doi: 10.1042/bj1860369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Robinson D., Willcox P. 4-Methylumbelliferyl phosphate as a substrate for lysosomal acid phosphatase. Biochim Biophys Acta. 1969 Sep 30;191(1):183–186. doi: 10.1016/0005-2744(69)90334-9. [DOI] [PubMed] [Google Scholar]
  18. Romslo I., Flatmark T. Energy-dependent accumulation of iron by isolated rat liver mitochondria. I. General features. Biochim Biophys Acta. 1973 Apr 27;305(1):29–40. doi: 10.1016/0005-2728(73)90228-4. [DOI] [PubMed] [Google Scholar]
  19. SAUNDERS S. J. IRON METABOLISM IN SYMPTOMATIC PORPHYRIA. A PRELIMINARY COMMUNICATION. S Afr J Lab Clin Med. 1963 Dec;14:277–282. [PubMed] [Google Scholar]
  20. Sandberg S., Romslo I. Phototoxicity of protoporphyrin as related to its subcellular localization in mice livers after short-term feeding with griseofulvin. Biochem J. 1981 Jul 15;198(1):67–74. doi: 10.1042/bj1980067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schnaitman C., Greenawalt J. W. Enzymatic properties of the inner and outer membranes of rat liver mitochondria. J Cell Biol. 1968 Jul;38(1):158–175. doi: 10.1083/jcb.38.1.158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Smith A. G., Cabral J. R., De Matteis F. A difference between two strains of rats in their liver non-haem iron content and in their response to the porphyrogenic effect of hexachlorobenzene. Chem Biol Interact. 1979 Oct;27(2-3):353–363. doi: 10.1016/0009-2797(79)90138-8. [DOI] [PubMed] [Google Scholar]
  23. Smith A. G., Francis J. E., Dinsdale D., Manson M. M., Cabral J. R. Hepatocarcinogenicity of hexachlorobenzene in rats and the sex difference in hepatic iron status and development of porphyria. Carcinogenesis. 1985 Apr;6(4):631–636. doi: 10.1093/carcin/6.4.631. [DOI] [PubMed] [Google Scholar]
  24. Stonard M. D. Experimental hepatic porphyria induced by hexachlorobenzene as a model for human symptomatic porphyria. Br J Haematol. 1974 Aug;27(4):617–625. doi: 10.1111/j.1365-2141.1974.tb06628.x. [DOI] [PubMed] [Google Scholar]
  25. Tangerås A., Flatmark T., Bäckström D., Ehrenberg A. Mitochondrial iron not bound in heme and iron-sulfur centers. Estimation, compartmentation and redox state. Biochim Biophys Acta. 1980 Feb 8;589(2):162–175. doi: 10.1016/0005-2728(80)90035-3. [DOI] [PubMed] [Google Scholar]
  26. Tangerås A. Iron content and degree of lipid peroxidation in liver mitochondria isolated from iron-loaded rats. Biochim Biophys Acta. 1983 May 4;757(1):59–68. [PubMed] [Google Scholar]
  27. Tangerås A. Mitochondrial iron not bound in heme and iron-sulfur centers and its availability for heme synthesis in vitro. Biochim Biophys Acta. 1985 Dec 13;843(3):199–207. doi: 10.1016/0304-4165(85)90140-0. [DOI] [PubMed] [Google Scholar]
  28. Tangerås A. Separation of haem compounds by reversed-phase ion-pair high-performance liquid chromatography and its application in the assay of ferrochelatase activity. J Chromatogr. 1984 Sep 14;310(1):31–39. doi: 10.1016/0378-4347(84)80065-1. [DOI] [PubMed] [Google Scholar]
  29. Vincent R., Nadeau D. Adjustment of the osmolality of Percoll for the isopycnic separation of cells and cell organelles. Anal Biochem. 1984 Sep;141(2):322–328. doi: 10.1016/0003-2697(84)90049-6. [DOI] [PubMed] [Google Scholar]

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