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

Authors: Wollam J; Magomedova L; Magner DB; Shen Y; Rottiers V; Motola DL; Mangelsdorf DJ; Cummins CL; Antebi A

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.

Keywords: Animals; Caenorhabditis elegans/cytology/*enzymology; Caenorhabditis elegans Proteins/genetics/metabolism; Cell Line; Cholesterol/metabolism; Chromatography, Liquid; Dehydrocholesterols/*metabolism; Gas Chromatography-Mass Spectrometry; Gene Expression Regulation, Developmental; Insects/cytology; *Longevity; Microsomes/metabolism; Neuroendocrine Cells/cytology/metabolism; Oxygenases/genetics/*metabolism; Phenotype; Receptors, Cytoplasmic and Nuclear/genetics/metabolism; Signal Transduction
Journal: Aging cell
Volume: 10
Issue: 5
Pages: 879-84
Date: July 14, 2011
PMID: 21749634
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Citation:

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 10: 879-84.


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