Skip to main content
SpringerLink
Log in

Localization of Cytochrome P450 in Membranes: Mitochondria

  • Chapter
Cytochrome P450

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 105))

Abstract

The occurrence of cytochrome P450 in mitochondria was first reported in 1964 (Harding et al. 1964). It was first found in the mitochondria isolated from adrenal cortex, and since then a wider distribution of various mitochondrial types of cytochrome P450 among animal organs has been confirmed. It is now known that all steroidogenic organs and some non-steroidogenic organs including liver and kidney contain cytochrome P450s in the mitochondria, and that the mitochondrial cytochrome P450s are distinct from their microsomal counterparts in the same cell. Some insect organs also contain a cytochrome P450 in the mitochondria which participates in the biosynthesis of metamorphosis hormones (Greenwood and Rees 1984). However, the occurrence of cytochrome P450 in mitochondria has not been confirmed for plants and eukaryotic microbes including yeasts.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Andersson S, Davis DL, Dahlback H, Jornvall H, Russell DW (1989) Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem 264: 8222–8229

    PubMed  CAS  Google Scholar 

  • Chashchin VL, Lapko VN, Adamovich TB, Lapko AG, Kuprina NS, Akhrem AA (1986) Primary structure of the cholesterol side-chain cleavage cytochrome P- 450 from bovine adrenocortical mitochondria and some aspects of its functioning on a structural level. Biochim Biophys Acta 871: 217–223

    Article  PubMed  CAS  Google Scholar 

  • Churchill PF, Kimura T (1979) Topological studies on cytochrome P-450SCC and P-45011ß in bovine adrenocortical inner mitochondrial membranes. Effects of controlled tryptic digestion. J Biol Chem 254: 10443–10448

    PubMed  CAS  Google Scholar 

  • DuBois RN, Simpson ER, Kramer RE, Waterman MR (1981) Induction of synthesis of cholesterol side chain cleavage cytochrome P-450 by adrenocorticotropin in cultured bovine adrenocortical cells. J Biol Chem 256: 7000–7005

    PubMed  CAS  Google Scholar 

  • Eilers M, Schatz G (1986) Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria. Nature 322: 228–232

    Article  PubMed  CAS  Google Scholar 

  • Greenwood DR, Rees HH (1984) Ecdysone 20-monooxygenase in the desert locust, Schistocerca gregaria. Biochem J 223: 837–847

    PubMed  CAS  Google Scholar 

  • Harding BW, Wong SH, Nelson DH (1964) Carbon monoxide-combining substances in rat adrenal. Biochim Biophys Acta 92: 415–417

    PubMed  CAS  Google Scholar 

  • Hawlitschek G, Schneider H, Schmidt B, Tropschug M, Hartl FU, Neupert W (1988) Mitochondrial protein import: Identification of processing protease and of PEP, a processing enhancing protein. Cell 53: 795–806

    Article  PubMed  CAS  Google Scholar 

  • Honkakoski P, Kojo A, Raunio H, Pasanen M, Juvonen R, Lang MA (1988) Hepatic mitochondrial coumarin 7-hydroxylase: comparison with the microsomal enzyme. Arch Biochem Biophys 267: 558–567

    Article  PubMed  CAS  Google Scholar 

  • Kumamoto T, Morohashi K, Ito A, Omura T (1987) Site-directed mutagenesis of basic amino acid residues in the extension peptide of P-450(SCC) Precursor: effects on the import of the precursor into mitochondria. J Biochem 102: 833–838

    PubMed  CAS  Google Scholar 

  • Kumamoto T, Ito A, Omura T (1989) Critical region in the extension peptide for the import of cytochrome P-450(SCC) precursor into mitochondria. J Biochem 105: 72–78

    PubMed  CAS  Google Scholar 

  • Mitani F, Shimizu T, Ueno R, Ishimura Y, Izumi S, Komatsu N, Watanabe K (1982) Cytochrome P-45011ß and P-450SCC in adrenal cortex: zonal distribution and intramitochondrial localization by the horseradish peroxidase-labeled antibody method. J Histochem Cytochem 30: 1066–1074

    Article  PubMed  CAS  Google Scholar 

  • Morohashi K, Fujii-Kuriyama Y, Okada Y, Sogawa K, Hirose T, Inayama S, Omura T (1984) Molecular cloning and nucleotide sequence of cDNA for mRNA of mitochondrial cytochrome P-450(SCC) of bovine adrenal cortex. Proc Natl Acad Sci USA 81: 4647–4651

    Article  PubMed  CAS  Google Scholar 

  • Morohashi K, Yoshioka H, Gotoh O, Okada Y, Yamamoto K, Miyata T, Sogawa K, Fujii-Kuriyama Y, Omura T (1987) Molecular cloning and nucleotide sequence of DNA of mitochondrial cytochrome P-450(11ß) of bovine adrenal cortex. J Biochem 102: 559–568

    PubMed  CAS  Google Scholar 

  • Nabi N, Kominami S, Takemori S, Omura T (1980) In vitro synthesis of mitochondrial cytochromes P-450(SCC) and P-450(11ß) and microsomal cytochrome P-450(C-21) by both free and bound polysomes isolated from bovine adrenal cortex. Biochem Biophys Res Comm 97: 687–693

    Article  PubMed  CAS  Google Scholar 

  • Nabi N, Kominami S, Takemori S, Omura T (1983) Contributions of cytoplasmic free and membrane-bound ribosomes to the synthesis of mitochondrial cytochrome P-450(SCC) and P-450(11ß) and microsomal cytochrome P-450(C- 21) in bovine adrenal cortex. J Biochem 94: 1517–1527

    PubMed  CAS  Google Scholar 

  • Neupert W, Schatz G (1981) How proteins are transported into mitochondria. Trends Biol Sci 6: 1–4

    Article  CAS  Google Scholar 

  • Niranjan BG, Wilson NM, Jefcoate CR, Avadhani NG (1984) Hepatic mitochondrial cytochrome P-450 system. Distinctive features of cytochrome P-450 involved in the activation of aflatoxin B1 and benzo[a]pyrene. J Biol Chem 259: 12495–12501

    PubMed  CAS  Google Scholar 

  • Niranjan BG, Raza H, Shayig RM, Jefcoate CR, Avadhani NG (1988) Hepatic mitochondrial cytochrome P-450 system. Identification and characterization of a precursor form of mitochondrial cytochrome P-450 induced by 3- methylcholanthrene. J Biol Chem 263: 575–580

    PubMed  CAS  Google Scholar 

  • Ogishima T, Okada Y, Omura T (1985) Import and processing of the precursor of cytochrome P-450(SCC) by bovine adrenal cortex mitochondria. J Biochem 98: 781–791

    PubMed  CAS  Google Scholar 

  • Omura T, Sanders E, Estabrook RW, Cooper Y, Rosenthal O (1966) Isolation from adrenal cortex of a nonheme iron protein and a flavoprotein functional as a reduced triphosphopyridine nucleotide-cytochrome P-450 reductase. Arch Biochem Biophys 117: 660–673

    Article  CAS  Google Scholar 

  • Omura T, Ito A (1991) Biosynthesis and intracellular sorting of mitochondrial forms of cytochrome P450. In: Waterman MR, Johnson EF (eds) Methods in enzymology, vol. 206. Academic, New York, pp. 75–81

    Google Scholar 

  • Ou WJ, Ito A, Morohashi K, Fujii-Kuriyama Y, Omura T (1986) Processing-independent in vitro translocation of cytochrome P450(SCC) precursor across mitochondrial membranes. J Biochem 100: 1287–1296

    PubMed  CAS  Google Scholar 

  • Ou WJ, Ito A, Okazaki H, Omura T (1989) Purification and characterization of a processing protease from rat liver mitochondria. EMBO J 8: 2605–2612

    PubMed  CAS  Google Scholar 

  • Pfanner N, Sollner T, Neupert W (1991) Mitochondrial import receptors for precursor proteins. TIBS 16: 63–67

    PubMed  Google Scholar 

  • Roise D, Schatz G (1988) Mitochondrial presenquences. J Biol Chem 263: 4509–4511

    PubMed  CAS  Google Scholar 

  • Roise D, Theiler F, Horvath SJ, Tomich JM, Richards JH, Allison DS, Schatz G (1988) Amphiphilicity is essential for mitochondrial presequence function. EMBO J 7: 649–653

    PubMed  CAS  Google Scholar 

  • Sakaguchi M, Mihara K, Sato R (1984) Signal recognition particle is required for co-translational insertion of cytochrome P-450 into microsomal membranes. Proc Natl Acad Sci USA 81: 3361–3364

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi M, Tomiyoshi R, Kuroiwa T, Mihara K, Omura T (1992) Functions of signal and signal-anchor sequences are determined by the balance between the hydrophobic segment and the N-terminal charge. Proc Natl Acad Sci USA 89: 16–19

    Article  PubMed  CAS  Google Scholar 

  • Sakaki T, Akiyoshi-Shibata M, Yabusaki Y, Ohkawa H (1992) Organella-targeted expression of rat liver cytochrome P450c27 in yeast: genetically engineered alteration of mitochondrial P450 into a microsomal form created a novel functional electron transport chain. J Biol Chem (in press)

    Google Scholar 

  • Sato T, Sakaguchi M, Mihara K, Omura T (1990) The amino-terminal structures that determine topological orientation of cytochrome P-450 in microsomal membrane. EMBO J 9: 2391–2397

    PubMed  CAS  Google Scholar 

  • Szczesna-Skorupa E, Browne N, Mead D, Kemper B (1988) Positive charges at the NH2 terminus converts the membrane-anchor signal peptide of cytochrome P-450 to a secretory signal peptide. Proc Natl Acad Sci USA 85: 738–742

    Article  PubMed  CAS  Google Scholar 

  • Usanov SA, Chernoglov AA, Chashchin VL (1989) Inhibitory domain specific antibodies to cytochrome P-450SCC. FEBS Lett 255: 125–128

    Article  PubMed  CAS  Google Scholar 

  • Usanov SA, Chernogolov AA, Chashchin VL (1990) Is cytochrome P-450SCc a transmembrane protein? FEBS Lett 275: 33–s35

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. T. Omura
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology, MC 1505, University of Connecticut Health Center, 263 Farmington Avenue, 06030, Farmington, CT, USA

    John B. Schenkman Ph.D.

  2. Institut für Toxikologie, Gesellschaft für Strahlen- und Umweltforschung mbH, Ingolstädter Landstr. 1, W-8042, Neuherberg, Fed. Rep. of Germany

    Helmut Greim M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Omura, T. (1993). Localization of Cytochrome P450 in Membranes: Mitochondria. In: Schenkman, J.B., Greim, H. (eds) Cytochrome P450. Handbook of Experimental Pharmacology, vol 105. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77763-9_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-77763-9_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-77765-3

  • Online ISBN: 978-3-642-77763-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation