Genetic regulation of unsaturated fatty acid composition in C. elegans.
Delta-9 desaturases, also known as stearoyl-CoA desaturases, are lipogenic enzymes responsible for the generation of vital components of membranes and energy storage molecules. We have identified a novel nuclear hormone receptor, NHR-80, that regulates delta-9 desaturase gene expression in Caenorhabditis elegans. Here we describe fatty acid compositions, lifespans, and gene expression studies of strains carrying mutations in nhr-80 and in the three genes encoding delta-9 desaturases, fat-5, fat-6, and fat-7. The delta-9 desaturase single mutants display only subtle changes in fatty acid composition and no other visible phenotypes, yet the fat-5;fat-6;fat-7 triple mutant is lethal, revealing that endogenous production of monounsaturated fatty acids is essential for survival. In the absence of FAT-6 or FAT-7, the expression of the remaining desaturases increases, and this ability to compensate depends on NHR-80. We conclude that, like mammals, C. elegans requires adequate synthesis of unsaturated fatty acids and maintains complex regulation of the delta-9 desaturases to achieve optimal fatty acid composition.
Brock
Trisha J
TJ
Institute of Biological Chemistry, Washington State University, Pullman, Washington, USA.
Browse
John
J
Watts
Jennifer L
JL
D000818:Animals; D017173:Caenorhabditis elegans; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000737:chemistry; D009154:Mutation; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D013379:Substrate Specificity
D005231:Fatty Acids, Unsaturated; D049452:Green Fluorescent Proteins; D013230:Stearoyl-CoA Desaturase