Joo Hyoe-Jin, Yim Yong-Hyeon, Jeong Pan-Young, Jin You-Xun, Lee Jeong-Eui, Kim Heekyeong, Jeong Seul-Ki, Chitwood David J, Paik Young-Ki
Department of Biochemistry, College of Life Sciences and Biotechnology, Yonsei Proteome Research Center, Yonsei University, Seoul, Republic of Korea.
Biochem J. 2009 Jul 29;422(1):61-71. doi: 10.1042/BJ20090513.
Caenorhabditis elegans excretes a dauer pheromone or daumone composed of ascarylose and a fatty acid side chain, the perception of which enables worms to enter the dauer state for long-term survival in an adverse environment. During the course of elucidation of the daumone biosynthetic pathway in which DHS-28 and DAF-22 are involved in peroxisomal beta-oxidation of VLCFAs (very long-chain fatty acids), we sought to investigate the physiological consequences of a deficiency in daumone biosynthesis in C. elegans. Our results revealed that two mutants, dhs-28(tm2581) and daf-22(ok693), lacked daumones and thus were dauer defective; this coincided with massive accumulation of fatty acyl-CoAs (up to 100-fold) inside worm bodies compared with levels in wild-type N2 worms. Furthermore, the deficiency in daumone biosynthesis and the massive accumulation of fatty acids and their acyl-CoAs caused severe developmental defects with reduced life spans (up to 30%), suggesting that daumone biosynthesis is be an essential part of C. elegans homoeostasis, affecting survival and maintenance of optimal physiological conditions by metabolizing some of the toxic non-permissible peroxisomal VLCFAs from the worm body in the form of readily excretable daumones.
秀丽隐杆线虫分泌一种由驱虫糖和脂肪酸侧链组成的滞育信息素或滞育酮，对其的感知能使线虫进入滞育状态，以便在不利环境中长期存活。在阐明滞育酮生物合成途径（其中DHS-28和DAF-22参与超长链脂肪酸（VLCFAs）的过氧化物酶体β-氧化）的过程中，我们试图研究秀丽隐杆线虫滞育酮生物合成缺陷的生理后果。我们的结果显示，两个突变体dhs-28(tm2581)和daf-22(ok693)缺乏滞育酮，因此存在滞育缺陷；与野生型N2线虫相比，这两个突变体虫体内的脂肪酰辅酶A大量积累（高达100倍）。此外，滞育酮生物合成缺陷以及脂肪酸及其酰基辅酶A的大量积累导致了严重的发育缺陷，寿命缩短（高达30%），这表明滞育酮生物合成是秀丽隐杆线虫体内平衡的重要组成部分，通过将虫体内一些有毒的、不允许存在的过氧化物酶体超长链脂肪酸以易于排泄的滞育酮形式代谢，从而影响生存和维持最佳生理状态。
