title: The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in steroidogenic pathways governing longevity.
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.
authors.affiliation: Department of Molecular and Cellular Biology, Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Wollam
authors.forename: Lilia
authors.initials: L
authors.lastname: Magomedova
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Magner
authors.forename: Yidong
authors.initials: Y
authors.lastname: Shen
authors.forename: Veerle
authors.initials: V
authors.lastname: Rottiers
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Motola
authors.forename: David J
authors.initials: DJ
authors.lastname: Mangelsdorf
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Cummins
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002853:Chromatography, Liquid; D003684:Dehydrocholesterols / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D018507:Gene Expression Regulation, Developmental; D007313:Insecta / Q000166:cytology; D008136:Longevity; D008861:Microsomes / Q000378:metabolism; D055099:Neuroendocrine Cells / Q000166:cytology / Q000378:metabolism; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; D003684:Dehydrocholesterols; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol; C016705:7-dehydrocholesterol; C510186:DAF-36 protein, C elegans; D010105:Oxygenases