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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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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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.
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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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DOI: https://doi.org/10.1038/nchembio.372
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