Open AccessThe Rieske oxygenase DAF‐36 functions as a cholesterol 7‐desaturase in steroidogenic pathways governing longevity
Author(s) -
Wollam Joshua,
Magomedova Lilia,
Magner Daniel B.,
Shen Yidong,
Rottiers Veerle,
Motola Daniel L.,
Mangelsdorf David J.,
Cummins Carolyn L.,
Antebi Adam
Publication year - 2011
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2011.00733.x
Subject(s) - biology , longevity , nuclear receptor , oxygenase , cholesterol , transcription factor , liver x receptor , sterol regulatory element binding protein , oxysterol , microbiology and biotechnology , enzyme , biochemistry , sterol , metabolism , gene , genetics
Summary 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.