Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jun 1989; 86(12): 4340–4344.
PMCID: PMC287264

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


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

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hartl FU, Pfanner N, Nicholson DW, Neupert W. Mitochondrial protein import. Biochim Biophys Acta. 1989 Jan 18;988(1):1–45. [PubMed]
  • Sherman F, Stewart JW. Genetics and biosynthesis of cytochrome c. Annu Rev Genet. 1971;5:257–296. [PubMed]
  • Zimmermann R, Paluch U, Neupert W. Cell-free synthesis of cytochrome c. FEBS Lett. 1979 Dec 1;108(1):141–146. [PubMed]
  • Stewart JW, Sherman F, Shipman NA, 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]
  • Matsuura S, Arpin M, Hannum C, Margoliash E, Sabatini DD, 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • 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]
  • Nicholson DW, Köhler H, Neupert W. Import of cytochrome c into mitochondria. Cytochrome c heme lyase. Eur J Biochem. 1987 Apr 1;164(1):147–157. [PubMed]
  • Hennig B, Neupert W. Biogenesis of cytochrome c in Neurospora crassa. Methods Enzymol. 1983;97:261–274. [PubMed]
  • Daum G, Böhni PC, 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]
  • Pelham HR, Jackson RJ. An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976 Aug 1;67(1):247–256. [PubMed]
  • Nicholson DW, 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]
  • Visco C, Taniuchi H, Berlett BS. 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]
  • 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • 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]
  • 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. [PubMed]

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


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...