Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1972 Aug;128(5):1043–1055. doi: 10.1042/bj1281043

The utilization of iron and its complexes by mammalian mitochondria

R Barnes 1, J L Connelly 1,*, O T G Jones 1
PMCID: PMC1173992  PMID: 4345350

Abstract

Sonicated mitochondria catalyse the reduction of ferric salts, and the subsequent incorporation of Fe2+ into haem, when provided with a reducing substrate such as succinate or NADH. The rate of haem synthesis was low under aerobic conditions and, after a short lag period, accelerated once anaerobic conditions were achieved; it was insensitive to antimycin A. The lag period was decreased by preincubating the mitochondria with NADH and Fe3+. Newly formed Fe2+ was autoxidized rapidly and the consequent O2 uptake was measured with an oxygen electrode to determine the rate of enzymic formation of Fe2+ from FeCl3; this reaction was rapid in sonicated mitochondria provided with NADH or succinate and was insensitive to antimycin A. The reaction was very slow in intact mitochondria, suggesting a permeability barrier to Fe3+ ions. This system was used to test the permeability of the mitochondrial membrane to various iron complexes of biological importance. Of the compounds tested only ferrioxamine G appeared to penetrate readily and the iron of this complex was reduced when intact mitochondria were supplied with succinate or NADH-linked substrates. The reduction was insensitive to rotenone or antimycin A. Both ferrioxamine G and ferrioxamine B were, however, reduced by particles. The membrane fraction of sonicated mitochondria was necessary for the reduction. The rate of ferrioxamine B reduction by sonicated mitochondria was measured by a dual-wavelength spectrophotometric assay and was found to be stimulated in conditions where the Fe2+ produced was utilized for haem synthesis. The addition of FeCl3 to anaerobic particles caused an oxidation of cytochrome b when this region of the respiratory chain was isolated by treatment with rotenone and antimycin A. These results suggest that the reduction of ferric iron and its complexes occurs inside the inner mitochondrial membrane in proximity to ferrochelatase. Possible sites for this reduction are the flavoproteins, succinate and NADH dehydrogenase.

Full text

PDF
1043

Selected References

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

  1. Atkin C. L., Neilands J. B., Phaff H. J. Rhodotorulic acid from species of Leucosporidium, Rhodosporidium, Rhodotorula, Sporidiobolus, and Sporobolomyces, and a new alanine-containing ferrichrome from Cryptococcus melibiosum. J Bacteriol. 1970 Sep;103(3):722–733. doi: 10.1128/jb.103.3.722-733.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chappell J. B. Systems used for the transport of substrates into mitochondria. Br Med Bull. 1968 May;24(2):150–157. doi: 10.1093/oxfordjournals.bmb.a070618. [DOI] [PubMed] [Google Scholar]
  3. Jones M. S., Jones O. T. Ferrochelatase of Rhodopseudomonas spheroides. Biochem J. 1970 Sep;119(3):453–462. doi: 10.1042/bj1190453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Jones O. T. Ferrochelatase of spinach chloroplasts. Biochem J. 1968 Mar;107(1):113–119. doi: 10.1042/bj1070113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Klingenberg M. Localization of the glycerol-phosphate dehydrogenase in the outer phase of the mitochondrial inner membrane. Eur J Biochem. 1970 Apr;13(2):247–252. doi: 10.1111/j.1432-1033.1970.tb00924.x. [DOI] [PubMed] [Google Scholar]
  7. LABBE R. F., HUBBARD N. Metal specificity of the ironprotoporphyrin chelating enzyme from rat liver. Biochim Biophys Acta. 1961 Sep 2;52:130–135. doi: 10.1016/0006-3002(61)90910-6. [DOI] [PubMed] [Google Scholar]
  8. MORRISON J. F. The activation of aconitase by ferrous ions and reducing agents. Biochem J. 1954 Dec;58(4):685–692. doi: 10.1042/bj0580685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. NEILANDS J. B. Some aspects of microbial iron metabolism. Bacteriol Rev. 1957 Jun;21(2):101–111. doi: 10.1128/br.21.2.101-111.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. PORRA R. J., JONES O. T. Studies on ferrochelatase. 1. Assay and properties of ferrochelatase from a pig-liver mitochondrial extract. Biochem J. 1963 Apr;87:181–185. doi: 10.1042/bj0870181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Primosigh J. V., Thomas E. D. Studies on the partition of iron in bone marrow cells. J Clin Invest. 1968 Jul;47(7):1473–1482. doi: 10.1172/JCI105841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sholnick P. L., Hammaker L. E., Marver H. S. Soluble hepatic delta-aminolevulinic acid synthetase: end-product inhibition of the partially purified enzyme. Proc Natl Acad Sci U S A. 1969 May;63(1):65–70. doi: 10.1073/pnas.63.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Singer T. P., Gutman M. The DPNH dehydrogenase of the mitochondrial respiratory chain. Adv Enzymol Relat Areas Mol Biol. 1971;34:79–153. doi: 10.1002/9780470122792.ch3. [DOI] [PubMed] [Google Scholar]
  15. Snow G. A. Mycobactins: iron-chelating growth factors from mycobacteria. Bacteriol Rev. 1970 Jun;34(2):99–125. doi: 10.1128/br.34.2.99-125.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Wang C. C., Newton A. An additional step in the transport of iron defined by the tonB locus of Escherichia coli. J Biol Chem. 1971 Apr 10;246(7):2147–2151. [PubMed] [Google Scholar]
  17. Wang C. C., Newton A. Iron transport in Escherichia coli: relationship between chromium sensitivity and high iron requirement in mutants of Escherichia coli. J Bacteriol. 1969 Jun;98(3):1135–1141. doi: 10.1128/jb.98.3.1135-1141.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Yoneyama Y., Tamai A., Yasuda T., Yoshikawa H. Iron-chelating enzyme from rat liver. Biochim Biophys Acta. 1965 Jul 29;105(1):100–105. doi: 10.1016/s0926-6593(65)80178-3. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES