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 language | English (US) |
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Pages (from-to) | 879-884 |
Number of pages | 6 |
Journal | Aging Cell |
Volume | 10 |
Issue number | 5 |
DOIs | |
State | Published - Oct 2011 |
Keywords
- Aging
- Bile acid
- Development
- Endocrine signaling
- Hormone
- Nuclear receptor
ASJC Scopus subject areas
- Aging
- Cell Biology