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PMID:18390550

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Citation

Entchev, EV, Schwudke, D, Zagoriy, V, Matyash, V, Bogdanova, A, Habermann, B, Zhu, L, Shevchenko, A and Kurzchalia, TV (2008) LET-767 is required for the production of branched chain and long chain fatty acids in Caenorhabditis elegans. J. Biol. Chem. 283:17550-60

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.

Links

PubMed Online version:10.1074/jbc.M800965200

Keywords

Alcohol Oxidoreductases/metabolism; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins/metabolism; Chromatography, Thin Layer; Computational Biology; Fatty Acids/metabolism; Lipids/chemistry; Mass Spectrometry; Models, Biological; Models, Chemical; Mutation; Phenotype; Phylogeny; RNA Interference; Triglycerides/chemistry

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:LE767

located_in

GO:0005783: endoplasmic reticulum

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:LE767

located_in

GO:0045179: apical cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:LE767

enables

GO:0050062: long-chain-fatty-acyl-CoA reductase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:LE767

involved_in

GO:0042759: long-chain fatty acid biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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