Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Jun;86(12):4340–4344. doi: 10.1073/pnas.86.12.4340

Import of cytochrome c into mitochondria: reduction of heme, mediated by NADH and flavin nucleotides, is obligatory for its covalent linkage to apocytochrome c.

D W Nicholson 1, W Neupert 1
PMCID: PMC287264  PMID: 2543970

Abstract

The covalent attachment of heme to apocytochrome c, and therefore the import of cytochrome c into mitochondria, is dependent on both NADH plus a cytosolic cofactor that has been identified to be FMN or FAD. NADH in concert with flavin nucleotides mediates the reduction of heme. Heme in the reduced state is a prerequisite for its covalent attachment to apocytochrome c by the enzyme cytochrome c heme lyase and thus for subsequent translocation of cytochrome c across the outer mitochondrial membrane during import.

Full text

PDF
4340

Selected References

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

  1. Daum G., Böhni P. C., Schatz G. Import of proteins into mitochondria. Cytochrome b2 and cytochrome c peroxidase are located in the intermembrane space of yeast mitochondria. J Biol Chem. 1982 Nov 10;257(21):13028–13033. [PubMed] [Google Scholar]
  2. Hartl F. U., Pfanner N., Nicholson D. W., Neupert W. Mitochondrial protein import. Biochim Biophys Acta. 1989 Jan 18;988(1):1–45. doi: 10.1016/0304-4157(89)90002-6. [DOI] [PubMed] [Google Scholar]
  3. Hennig B., Koehler H., Neupert W. Receptor sites involved in posttranslational transport of apocytochrome c into mitochondria: specificity, affinity, and number of sites. Proc Natl Acad Sci U S A. 1983 Aug;80(16):4963–4967. doi: 10.1073/pnas.80.16.4963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hennig B., Neupert W. Biogenesis of cytochrome c in Neurospora crassa. Methods Enzymol. 1983;97:261–274. doi: 10.1016/0076-6879(83)97138-0. [DOI] [PubMed] [Google Scholar]
  5. Matsuura S., Arpin M., Hannum C., Margoliash E., Sabatini D. D., Morimoto T. In vitro synthesis and posttranslational uptake of cytochrome c into isolated mitochondria: role of a specific addressing signal in the apocytochrome. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4368–4372. doi: 10.1073/pnas.78.7.4368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Nicholson D. W., Hergersberg C., Neupert W. Role of cytochrome c heme lyase in the import of cytochrome c into mitochondria. J Biol Chem. 1988 Dec 15;263(35):19034–19042. [PubMed] [Google Scholar]
  7. Nicholson D. W., Köhler H., Neupert W. Import of cytochrome c into mitochondria. Cytochrome c heme lyase. Eur J Biochem. 1987 Apr 1;164(1):147–157. doi: 10.1111/j.1432-1033.1987.tb11006.x. [DOI] [PubMed] [Google Scholar]
  8. Pelham H. R., Jackson R. J. An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976 Aug 1;67(1):247–256. doi: 10.1111/j.1432-1033.1976.tb10656.x. [DOI] [PubMed] [Google Scholar]
  9. Schleyer M., Neupert W. Transport of proteins into mitochondria: translocational intermediates spanning contact sites between outer and inner membranes. Cell. 1985 Nov;43(1):339–350. doi: 10.1016/0092-8674(85)90039-x. [DOI] [PubMed] [Google Scholar]
  10. Sherman F., Stewart J. W. Genetics and biosynthesis of cytochrome c. Annu Rev Genet. 1971;5:257–296. doi: 10.1146/annurev.ge.05.120171.001353. [DOI] [PubMed] [Google Scholar]
  11. Stewart J. W., Sherman F., Shipman N. A., Jackson M. Identification and mutational relocation of the AUG codon initiating translation of iso-1-cytochrome c in yeast. J Biol Chem. 1971 Dec 25;246(24):7429–7445. [PubMed] [Google Scholar]
  12. Taketani S., Tanaka-Yoshioka A., Masaki R., Tashiro Y., Tokunaga R. Association of ferrochelatase with Complex I in bovine heart mitochondria. Biochim Biophys Acta. 1986 Sep 4;883(2):277–283. doi: 10.1016/0304-4165(86)90319-3. [DOI] [PubMed] [Google Scholar]
  13. Teintze M., Slaughter M., Weiss H., Neupert W. Biogenesis of mitochondrial ubiquinol:cytochrome c reductase (cytochrome bc1 complex). Precursor proteins and their transfer into mitochondria. J Biol Chem. 1982 Sep 10;257(17):10364–10371. [PubMed] [Google Scholar]
  14. Veloso D., Basile G., Taniuchi H. Formation of a cytochrome c-like species from horse apoprotein and hemin catalyzed by yeast mitochondrial cytochrome c synthetase. J Biol Chem. 1981 Aug 25;256(16):8646–8651. [PubMed] [Google Scholar]
  15. Visco C., Taniuchi H., Berlett B. S. On the specificity of cytochrome c synthetase in recognition of the amino acid sequence of apocytochrome c. J Biol Chem. 1985 May 25;260(10):6133–6138. [PubMed] [Google Scholar]
  16. Zimmermann R., Hennig B., Neupert W. Different transport pathways of individual precursor proteins in mitochondria. Eur J Biochem. 1981 Jun 1;116(3):455–460. doi: 10.1111/j.1432-1033.1981.tb05357.x. [DOI] [PubMed] [Google Scholar]
  17. Zimmermann R., Paluch U., Neupert W. Cell-free synthesis of cytochrome c. FEBS Lett. 1979 Dec 1;108(1):141–146. doi: 10.1016/0014-5793(79)81196-5. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES