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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

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1437-4315
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Volume 386, Issue 5 (May 2005)

Issues

Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria

Evi Derouet-Hümbert
  • Department of Biochemistry, Building No. 9.2, Saarland University, D-66041 Saarbrücken, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Klaus Roemer
  • Department of Virology, Building No. 47, University of Saarland Medical School, D-66421 Homburg/Saar, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Matthias Bureik
  • Department of Biochemistry, Building No. 9.2, Saarland University, D-66041 Saarbrücken, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2005-07-05 | DOI: https://doi.org/10.1515/BC.2005.054

Abstract

Mitochondrial cytochrome P450 systems are an indispensable component of mammalian steroid biosynthesis; they catalyze regio- and stereo-specific steroid hydroxylations and consist of three protein entities: adrenodoxin reductase (AdR), adrenodoxin (Adx), and a mitochondrial cytochrome P450 enzyme, e.g., CYP11A1 (P450 side chain cleavage, P450scc). It is known that the latter two are able to generate reactive oxygen species (ROS) in vitro. In this study, we investigated whether this ROS generation also occurs in vivo and, if so, whether it leads to the induction of apoptosis. We found that overexpression of either human or bovine Adx causes a significant loss of viability in 11 different cell lines. This loss of viability does not depend on the presence of the tumor suppressor protein p53. Transient overexpression of human Adx in HCT116 cells leads to ROS production, to a disruption of the mitochondrial transmembrane potential (ΔΨ), to cytochrome c release from the mitochondria, and to caspase activation. In contrast, the effect of transient overexpression of human CYP11A1 on cell viability varies in different cell lines, with some being sensitive and others not. We conclude that mitochondrial cytochrome P450 systems are a source of mitochondrial ROS production and can play a role in the induction of mitochondrial apoptosis.

Keywords: adrenodoxin; apoptosis; CYP11A1; cytochrome P450; electron transfer chain; mitochondria; reactive oxygen species; steroid hydroxylation

About the article

Corresponding author


Received: October 29, 2004

Accepted: February 25, 2005

Published Online: 2005-07-05

Published in Print: 2005-05-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2005.054.

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