Journal Article

Acyl-CoA oxidase complexes control the chemical message produced by Caenorhabditis elegans

Chinta, Satya, Zhang, Xinxing, Feng, Likui, Singh, Prashant, Nunnery, Joshawna K., Butcher, Rebecca A., Wang, Yuting

2015

Overview

SignificanceMany free-living and parasitic nematode (roundworm) species use pheromones called ascarosides to control their development and behavior. The molecular mechanisms by which environmental factors influence pheromone composition are unknown. The side chains of the ascarosides are derived from long-chain fatty acids that are shortened through β-oxidation cycles. In this manuscript, we show that three acyl-CoA oxidases, which catalyze the first step in the β-oxidation cycles, form specific homo- and heterodimers with different side-chain length preferences. Stressful conditions induce the expression of specific acyl-CoA oxidases, resulting in corresponding changes in pheromone composition. Thus, our work demonstrates how environmental conditions can influence the chemical message that nematodes communicate to other roundworms in the population. Caenorhabditis elegans uses ascaroside pheromones to induce development of the stress-resistant dauer larval stage and to coordinate various behaviors. Peroxisomal β-oxidation cycles are required for the biosynthesis of the fatty acid-derived side chains of the ascarosides. Here we show that three acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, form different protein homo- and heterodimers with distinct substrate preferences. Mutations in the acyl-CoA oxidase genes acox-1, -2, and -3 led to specific defects in ascaroside production. When the acyl-CoA oxidases were expressed alone or in pairs and purified, the resulting acyl-CoA oxidase homo- and heterodimers displayed different side-chain length preferences in an in vitro activity assay. Specifically, an ACOX-1 homodimer controls the production of ascarosides with side chains with nine or fewer carbons, an ACOX-1/ACOX-3 heterodimer controls the production of those with side chains with seven or fewer carbons, and an ACOX-2 homodimer controls the production of those with ω-side chains with less than five carbons. Our results support a biosynthetic model in which β-oxidation enzymes act directly on the CoA-thioesters of ascaroside biosynthetic precursors. Furthermore, we identify environmental conditions, including high temperature and low food availability, that induce the expression of acox-2 and/or acox-3 and lead to corresponding changes in ascaroside production. Thus, our work uncovers an important mechanism by which C. elegans increases the production of the most potent dauer pheromones, those with the shortest side chains, under specific environmental conditions.

• Publisher: National Academy of Sciences
• Subject: acyl coenzyme A / Acyl-CoA Oxidase - metabolism / Animals / beta oxidation / Biochemistry / Biological Sciences / Biosynthesis / Caenorhabditis elegans / Caenorhabditis elegans - enzymology / Catalysis / chemical control / Chromatography, Liquid / Environmental conditions / environmental factors / Food availability / Genes / High temperature / long chain fatty acids / Mutation / Nematodes / Oxidation / Oxygen - metabolism / Pheromones / Pheromones - metabolism / Polymerase Chain Reaction / Protein Multimerization / Substrate Specificity / Tandem Mass Spectrometry / Temperature