Submitted to: Biochemical Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/4/2009
Publication Date: 8/15/2009
Publication URL: http://hdl.handle.net/10113/42082
Citation: Joo, H.J., Wim, Y.H., Jeong, P.Y., Jin, Y.X., Lee, J.E., Kim, H., Jeong, S.K., Chitwood, D.J., Paik, Y.K. 2009. Caenorhabditis elegans utilizes dauer pheromone biosynthesis to dispose of toxic peroxisomal fatty acids for cellular homoeostasis. Biochemical Journal. 422(1):61-71. Interpretive Summary: Nematodes are microscopic worms that attack plant roots and annually cause ten billion dollars of crop losses in the United States. A major problem with reducing nematode-induced crop losses is that safe and effective control measures for nematodes are not available. Many nematodes secrete natural chemicals called pheromones that cause other nematodes to produce specialized resting stages that are resistant to unfavorable environments. Therefore, one approach to developing new control measures is to interfere with the production of these natural pheromones, resulting in the inability of nematodes to survive adverse environments. In this paper, we report the discovery of the genes that are involved in the synthesis of these pheromones by a nonparasitic, bacterial-feeding nematode. We also show that when these genes are made dysfunctional, the nematodes cease growing and accumulate unusual fat globules. The results are significant because they provide the first evidence that these specific genes are involved in the biosynthesis of pheromones by nematodes. Consequently, the results will be used by scientists who are developing new methods for crop nematode control by interfering with the production of the natural compounds they produce that enable them to survive.
Technical Abstract: Caenorhabditis elegans secretes a dauer pheromone or daumone composed of ascarylose and a fatty acid side chain, perception of which enables worms to gauge depletion of food or a high worm population density. As a result, worms enter the dauer state, a specific developmental stage capable of surviving long periods of time in an adverse environment. To elucidate both the mechanism of daumone biosynthesis and its physiological function in C. elegans, we examined two enzymes involved in peroxisomal ß-oxidation, DHS-28 and SCPx, and corresponding mutant genes, dhs-28(tm2581) and scpx(ok693). The results indicate that the ascarylose moiety is synthesized de novo and that peroxisomal beta-oxidation of long-chain methyl-branched fatty acid (MBFA) is required for daumone biosynthesis. Dauer assays and chemical analyses revealed that two mutant C. elegans strains, dhs-28(tm2581) and scpx(ok693), lacked daumones and were dauer defective; this coincided with massive accumulation of long-chain fatty acids (up to 3.8-fold) and their acyl-CoAs (up to 100-fold) inside worm bodies compared to levels in wild type N2 worms. Furthermore, the deficiency in daumone biosynthesis and the massive accumulation of MBFAs were associated with developmental defects as well as reduced life spans, suggesting that daumone biosynthesis through peroxisomal beta-oxidation in part appears to be a key part of C. elegans homeostasis, which thereby affecting survival and maintenance of optimal physiological conditions by eliminating toxic MBFAs and their acyl-CoAs from the worm body in the form of readily excretable water-soluble daumones.