Reference - Detail
|Author||Ruiz M, Bodhicharla R, Svensk E, Devkota R, Busayavalasa K, Palmgren H, Ståhlman M, Boren J, Pilon M.|
|Title||Membrane fluidity is regulated by the C. elegans transmembrane protein FLD-1 and its human homologs TLCD1/2.|
Dietary fatty acids are the main building blocks for cell membranes in animals, and mechanisms must therefore exist that compensate for dietary variations. We isolated C. elegans mutants that improved tolerance to dietary saturated fat in a sensitized genetic background, including eight alleles of the novel gene fld-1 that encodes a homolog of the human TLCD1 and TLCD2 transmembrane proteins. FLD-1 is localized on plasma membranes and acts by limiting the levels of highly membrane-fluidizing long-chain polyunsaturated fatty acid-containing phospholipids. Human TLCD1/2 also regulate membrane fluidity by limiting the levels of polyunsaturated fatty acid-containing membrane phospholipids. FLD-1 and TLCD1/2 do not regulate the synthesis of long-chain polyunsaturated fatty acids but rather limit their incorporation into phospholipids. We conclude that inhibition of FLD-1 or TLCD1/2 prevents lipotoxicity by allowing increased levels of membrane phospholipids that contain fluidizing long-chain polyunsaturated fatty acids.
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|MeSH||Alleles Amino Acid Sequence Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Cell Membrane / metabolism Epistasis, Genetic Genes, Suppressor Green Fluorescent Proteins / metabolism Humans Membrane Fluidity* Membrane Proteins / chemistry Membrane Proteins / genetics Membrane Proteins / metabolism* Membrane Proteins / physiology Mice Mutation / genetics Organ Specificity Phenotype Phospholipids / metabolism Receptors, Adiponectin / metabolism Sequence Homology, Amino Acid*|