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学術論文

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

MPS-Authors

Wollam, J.
Max Planck Society;

Magomedova, L.
Max Planck Society;

Magner, D. B.
Max Planck Society;

Shen, Y.
Max Planck Society;

Rottiers, V.
Max Planck Society;

Motola, D. L.
Max Planck Society;

Mangelsdorf, D. J.
Max Planck Society;

Cummins, C. L.
Max Planck Society;

Antebi, A.
Max Planck Society;

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引用

Wollam, J., Magomedova, L., Magner, D. B., Shen, Y., Rottiers, V., Motola, D. L., Mangelsdorf, D. J., Cummins, C. L., & Antebi, A. (2011). The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in steroidogenic pathways governing longevity. Aging Cell, 10(5), 879-84. doi:10.1111/j.1474-9726.2011.00733.x.

要旨

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.