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

33 Citations (Scopus)

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

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Oxygenases
Cholesterol
Cytoplasmic and Nuclear Receptors
Bile Acids and Salts
Sterols
Transcription Factors
Steroids
Enzymes
dafachronic acid

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Wollam, J., Magomedova, L., Magner, D. B., Shen, Y., Rottiers, V., Motola, D. 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

The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in steroidogenic pathways governing longevity. / Wollam, Joshua; Magomedova, Lilia; Magner, Daniel B.; Shen, Yidong; Rottiers, Veerle; Motola, Daniel L.; Mangelsdorf, David J.; Cummins, Carolyn L.; Antebi, Adam.

In: Aging Cell, Vol. 10, No. 5, 10.2011, p. 879-884.

Research output: Contribution to journalArticle

Wollam, J, Magomedova, L, Magner, DB, Shen, Y, Rottiers, V, Motola, DL, Mangelsdorf, DJ, Cummins, CL & Antebi, A 2011, 'The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in steroidogenic pathways governing longevity', Aging Cell, vol. 10, no. 5, pp. 879-884. https://doi.org/10.1111/j.1474-9726.2011.00733.x
Wollam, Joshua ; Magomedova, Lilia ; Magner, Daniel B. ; Shen, Yidong ; Rottiers, Veerle ; Motola, Daniel L. ; Mangelsdorf, David J. ; Cummins, Carolyn L. ; Antebi, Adam. / The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in steroidogenic pathways governing longevity. In: Aging Cell. 2011 ; Vol. 10, No. 5. pp. 879-884.
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