The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in steroidogenic pathways governing longevity

Joshua Wollam, Lilia Magomedova, Daniel B. Magner, Yidong Shen, Veerle Rottiers, Daniel L. Motola, David J. Mangelsdorf, Carolyn L. Cummins, Adam Antebi

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Bile acids are cholesterol-derived signaling molecules that regulate mammalian metabolism through sterol-sensing nuclear receptor transcription factors. In C. elegans, bile acid-like steroids called dafachronic acids (DAs) control developmental timing and longevity by activating the nuclear receptor DAF-12. However, little is known about the biosynthesis of these molecules. Here, we show that the DAF-36/Rieske oxygenase works at the first committed step, converting cholesterol to 7-dehydrocholesterol. Its elucidation as a cholesterol 7-desaturase provides crucial biochemical evidence that such oxygenases are key steroidogenic enzymes. By controlling DA production, DAF-36 regulates DAF-12 activities for reproductive development and longevity and may illuminate related pathways in metazoans.

Original languageEnglish (US)
Pages (from-to)879-884
Number of pages6
JournalAging Cell
Volume10
Issue number5
DOIs
StatePublished - Oct 2011

Keywords

  • Aging
  • Bile acid
  • Development
  • Endocrine signaling
  • Hormone
  • Nuclear receptor

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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    Wollam, J., Magomedova, L., Magner, D. B., Shen, Y., Rottiers, V., Motola, D. L., Mangelsdorf, D. J., Cummins, C. L., & Antebi, A. (2011). The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in steroidogenic pathways governing longevity. Aging Cell, 10(5), 879-884. https://doi.org/10.1111/j.1474-9726.2011.00733.x