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

Aging Cell. 2011 Oct;10(5):879-84. doi: 10.1111/j.1474-9726.2011.00733.x. Epub 2011 Aug 7.

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 types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Line
  • Cholesterol / metabolism
  • Chromatography, Liquid
  • Dehydrocholesterols / metabolism*
  • Gas Chromatography-Mass Spectrometry
  • Gene Expression Regulation, Developmental
  • Insecta / cytology
  • Longevity*
  • Microsomes / metabolism
  • Neuroendocrine Cells / cytology
  • Neuroendocrine Cells / metabolism
  • Oxygenases / genetics
  • Oxygenases / metabolism*
  • Phenotype
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction

Substances

  • Caenorhabditis elegans Proteins
  • DAF-12 protein, C elegans
  • Dehydrocholesterols
  • Receptors, Cytoplasmic and Nuclear
  • Cholesterol
  • 7-dehydrocholesterol
  • DAF-36 protein, C elegans
  • Oxygenases