Department of Molecular and Cellular Biology, Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Aging Cell. 2011 Oct;10(5):879-84. doi: 10.1111/j.1474-9726.2011.00733.x. Epub 2011 Aug 7.
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.
胆酸是胆固醇衍生的信号分子，通过固醇感应核受体转录因子调节哺乳动物的代谢。在秀丽隐杆线虫中，胆酸样甾体称为 dauer 激活因子（DA），通过激活核受体 DAF-12 来控制发育时间和寿命。然而，这些分子的生物合成知之甚少。在这里，我们表明 DAF-36/Rieske 加氧酶在第一步起作用，将胆固醇转化为 7-脱氢胆固醇。它作为胆固醇 7-去饱和酶的阐明提供了重要的生化证据，表明此类加氧酶是关键的甾体生成酶。通过控制 DA 的产生，DAF-36 调节 DAF-12 活性，从而影响生殖发育和寿命，并可能阐明后生动物中的相关途径。
