title: Caenorhabditis elegans utilizes dauer pheromone biosynthesis to dispose of toxic peroxisomal fatty acids for cellular homoeostasis.
abstract: 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.
authors.affiliation: Department of Biochemistry, College of Life Sciences and Biotechnology, Yonsei Proteome Research Center, Yonsei University, Seoul, Republic of Korea.
authors.forename: Hyoe-Jin
authors.initials: HJ
authors.lastname: Joo
authors.forename: Yong-Hyeon
authors.initials: YH
authors.lastname: Yim
authors.forename: Pan-Young
authors.initials: PY
authors.lastname: Jeong
authors.forename: You-Xun
authors.initials: YX
authors.lastname: Jin
authors.forename: Jeong-Eui
authors.initials: JE
authors.lastname: Lee
authors.forename: Heekyeong
authors.initials: H
authors.lastname: Kim
authors.forename: Seul-Ki
authors.initials: SK
authors.lastname: Jeong
authors.forename: David J
authors.initials: DJ
authors.lastname: Chitwood
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Paik
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D047108:Embryonic Development; D005227:Fatty Acids / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D006601:Hexoses / Q000096:biosynthesis; D006706:Homeostasis; D008136:Longevity; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000378:metabolism*; D010641:Phenotype; D010675:Pheromones / Q000096:biosynthesis*
chemical_list: D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; D006601:Hexoses; D010675:Pheromones; C496586:daumone, C elegans; C009616:tyvelose