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| Subject Categories: Cellular Metabolism |
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| The EMBO Journal
(2007) 26, 5109–5119, doi:10.1038/sj.emboj.7601924 Published online 22 November 2007 |
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| An acetylation/deacetylation cycle controls the export of sterols and steroids from S. cerevisiae |
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| Rashi Tiwari, René Köffel1 and Roger Schneiter |
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Department of Medicine, Division of Biochemistry, Institute of Biochemistry, University of Fribourg, Fribourg, Switzerland To whom correspondence should be addressed Roger Schneiter, Department of Medicine, Division of Biochemistry, Institute of Biochemistry, University of Fribourg, Chemin du Musée 5, Fribourg 1700, Switzerland. Tel.: +41 26 300 8654; Fax: +41 26 300 9735; E-mail: roger.schneiter@unifr.ch 1 Present address: Institute of Immunology, Medical University Vienna, Lazarettgasse 19, Wien 1090, Austria Received 5 June 2007; Accepted 19 October 2007; Published online 22 November 2007. |
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| Abstract |
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| Sterol homeostasis in eukaryotic cells relies on the reciprocal interconversion of free sterols and steryl esters. Here we report the identification of a novel reversible sterol modification in yeast, the sterol acetylation/deacetylation cycle. Sterol acetylation requires the acetyltransferase ATF2, whereas deacetylation requires SAY1, a membrane-anchored deacetylase with a putative active site in the ER lumen. Lack of SAY1 results in the secretion of acetylated sterols into the culture medium, indicating that the substrate specificity of SAY1 determines whether acetylated sterols are secreted from the cells or whether they are deacetylated and retained. Consistent with this proposition, we find that acetylation and export of the steroid hormone precursor pregnenolone depends on its acetylation by ATF2, but is independent of SAY1-mediated deacetylation. Cells lacking Say1 or Atf2 are sensitive against the plant-derived allylbenzene eugenol and both Say1 and Atf2 affect pregnenolone toxicity, indicating that lipid acetylation acts as a detoxification pathway. The fact that homologues of SAY1 are present in the mammalian genome and functionally substitute for SAY1 in yeast indicates that part of this pathway has been evolutionarily conserved. |
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| Keywords: cholesteryl acetate, detoxification, secretory pathway, sterol esterase, yeast |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHSeparation of parathyroid hormone and calcitonin-sensitive cells from non-responsive bone cells Nature Letters to Editor (20 Dec 1974) An acetylation/deacetylation cycle controls the export of sterols and steroids from S. cerevisiae The EMBO Journal Article Self-sufficient biosynthesis of pregnenolone and progesterone in engineered yeast Nature Biotechnology Research Article (01 Feb 1998) Total biosynthesis of hydrocortisone from a simple carbon source in yeast Nature Biotechnology Research (01 Feb 2003) |
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