title: dif-1 and colt, both implicated in early embryonic development, encode carnitine acylcarnitine translocase.
abstract: It has always been assumed that during development the embryo and fetus depend only on glycolysis for energy generation and that they do not oxidize fatty acids. Recently, however, we found abundant expression and activity of fatty acid oxidation (FAO) enzymes in the human embryo and fetus. In a search for FAO gene expression during development we came across two embryonic differentiation genes: differentiation defective (dif-1) and congested-like trachea (colt) of Caenorhabditis elegans and Drosophila melanogaster, respectively. Earlier studies showed that expression of these two genes is essential during developmental stages with high energy requirements. Both dif-1 and colt encode proteins with sequence similarity to the mitochondrial carnitine acylcarnitine carrier (CACT), which suggests that the DIF-1 and COLT proteins might be functional orthologues of CACT. To investigate this, we expressed both dif-1 and colt in Saccharomyces cerevisiae. Our results show that DIF-1 and COLT can functionally complement a yeast CACT deletion strain and thus function as carnitine acylcarnitine transporters. This finding is well in line with the recent observation that embryos are capable of oxidizing fatty acids and furthermore implies that FAO is essential during early embryonic development when the energy demand is high.
authors.affiliation: Department of Pediatrics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Oey
authors.forename: Lodewijk
authors.initials: L
authors.lastname: Ijlst
authors.forename: Carlo W T
authors.initials: CW
authors.lastname: van Roermund
authors.forename: Frits A
authors.initials: FA
authors.lastname: Wijburg
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis* / Q000235:genetics; D002333:Carnitine Acyltransferases / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster / Q000201:enzymology; D047108:Embryonic Development; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: C110283:COLT protein, Drosophila; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C093960:DIF-1 protein, C elegans; D029721:Drosophila Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D002333:Carnitine Acyltransferases