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- Title
The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in steroidogenic pathways governing longevity.
- Authors
Wollam, Joshua; Magomedova, Lilia; Magner, Daniel B; Shen, Yidong; Rottiers, Veerle; Motola, Daniel L; Mangelsdorf, David J; Cummins, Carolyn L; Antebi, Adam
- 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.
- Publication
Aging cell, 2011, Vol 10, Issue 5, p879
- ISSN
1474-9726
- Publication type
Journal Article
- DOI
10.1111/j.1474-9726.2011.00733.x