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4-Nitrobenzoate inhibits coenzyme Q biosynthesis in mammalian cell cultures

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Abstract

Coenzyme Q (Q) is an electron transporter in the respiratory chain and a lipid-soluble antioxidant that decreases in humans with age. Here we show that 4-nitrobenzoate inhibited 4-hydroxybenzoate:polyprenyl transferase (Coq2) in a competitive manner and dose-dependently decreased Q in mammalian cells without accumulation of Q intermediates. As 4-nitrobenzoate neither interfered with mitochondrial respiration nor induced oxidative stress, it should prove a valuable tool for studies on both Q deficiency and Q supplementation.

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Figure 1: Characterization of Coq2 inhibition with 4-NB.
Figure 2: 4-HB and decylubiquinone but not Q10 rescued the decreased respiration in 4-NB treated 3T3-Swiss cells.

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Acknowledgements

We thank T. Chojnacki (Institute of Biochemistry and Biophysics, Polish Academy of Sciences) for kindly providing the various radioactive and non-radioactive isoprenoids. We are also indebted to J.W. DePierre and B.D. Nelson (Department of Biochemistry and Biophysics, Stockholm Univ.) for valuable discussions during preparation of the manuscript. This work was supported by the Loo and Hans Osterman Foundation for Geriatric Research, the Ollie and Elof Ericsson Foundation, the O.E. and Edla Johansson Foundation, the Helge Ax:son Johnson foundation and the Carl Trygger Foundation.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden

    Ulrika Forsman, Mats Sjöberg, Mikael Turunen & Pavel J Sindelar

  2. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden

    Pavel J Sindelar

Authors
  1. Ulrika Forsman
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  2. Mats Sjöberg
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  3. Mikael Turunen
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  4. Pavel J Sindelar
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Contributions

U.F., M.S. and M.T. performed the experiments. U.F. and P.J.S. designed the experiments, interpreted the data and wrote the manuscript. P.J.S. conceived the project.

Corresponding author

Correspondence to Pavel J Sindelar.

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The authors declare no competing financial interests.

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Supplementary Text and Figures

Supplementary Figures 1–7, Supplementary Tables 1–3 and Supplementary Methods (PDF 931 kb)

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Forsman, U., Sjöberg, M., Turunen, M. et al. 4-Nitrobenzoate inhibits coenzyme Q biosynthesis in mammalian cell cultures. Nat Chem Biol 6, 515–517 (2010). https://doi.org/10.1038/nchembio.372

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