title: LET-767 is required for the production of branched chain and long chain fatty acids in Caenorhabditis elegans.
abstract: LET-767 from Caenorhabditis elegans belongs to a family of short chain dehydrogenases/reductases and is homologous to 17beta-hydroxysterol dehydrogenases of type 3 and 3-ketoacyl-CoA reductases. Worms subjected to RNA interference (RNAi) of let-767 displayed multiple growth and developmental defects in the first generation and arrested in the second generation as L1 larvae. To determine the function of LET-767 in vivo, we exploited a biochemical complementation approach, in which let-767 (RNAi)-arrested larvae were rescued by feeding with compounds isolated from wild type worms. The arrest was only rescued by the addition of triacylglycerides extracted from worms but not from various natural sources, such as animal fats and plant oils. The mass spectrometric analyses showed alterations in the fatty acid content of triacylglycerides. Essential for the rescue were odd-numbered fatty acids with monomethyl branched chains. The rescue was improved when worms were additionally supplemented with long chain even-numbered fatty acids. Remarkably, let-767 completely rescued the yeast 3-ketoacyl-CoA reductase mutant (ybr159Delta). Because worm ceramides exclusively contain a monomethyl branched chain sphingoid base, we also investigated ceramides in let-767 (RNAi). Indeed, the amount of ceramides was greatly reduced, and unusual sphingoid bases were observed. Taken together, we conclude that LET-767 is a major 3-ketoacyl-CoA reductase in C. elegans required for the bulk production of monomethyl branched and long chain fatty acids, and the developmental arrest in let-767 (RNAi) worms is caused by the deficiency of the former.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
authors.forename: Eugeni V
authors.initials: EV
authors.lastname: Entchev
authors.forename: Dominik
authors.initials: D
authors.lastname: Schwudke
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Zagoriy
authors.forename: Vitali
authors.initials: V
authors.lastname: Matyash
authors.forename: Aliona
authors.initials: A
authors.lastname: Bogdanova
authors.forename: Bianca
authors.initials: B
authors.lastname: Habermann
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Andrej
authors.initials: A
authors.lastname: Shevchenko
authors.forename: Teymuras V
authors.initials: TV
authors.lastname: Kurzchalia
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D019295:Computational Biology; D005227:Fatty Acids / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D013058:Mass Spectrometry; D008954:Models, Biological; D008956:Models, Chemical; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D034622:RNA Interference; D014280:Triglycerides / Q000737:chemistry
chemical_list: D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; D008055:Lipids; D014280:Triglycerides; D000429:Alcohol Oxidoreductases; C525834:LET-767 protein, C elegans