Disruption of the Saccharomyces cerevisiae homologue to the murine fatty acid transport protein impairs uptake and growth on long-chain fatty acids.
The yeast Saccharomyces cerevisiae is able to utilize exogenous fatty acids for a variety of cellular processes including beta-oxidation, phospholipid biosynthesis, and protein modification. The molecular mechanisms that govern the uptake of these compounds in S. cerevisiae have not been described. We report the characterization of FAT1, a gene that encodes a putative membrane-bound long-chain fatty acid transport protein (Fat1p). Fat1p contains 623 amino acid residues that are 33% identical and 54% with similar chemical properties as compared with the fatty acid transport protein FATP described in 3T3-L1 adipocytes (Schaffer and Lodish (1994) Cell 79, 427-436), suggesting a similar function. Disruption of FAT1 results in 1) an impaired growth in YPD medium containing 25 microM cerulenin and 500 microM fatty acid (myristate (C14:0), palmitate (C16:0), or oleate (C18:1)); 2) a marked decrease in the uptake of the fluorescent long-chain fatty acid analogue boron dipyrromethene difluoride dodecanoic acid (BODIPY-3823); 3) a reduced rate of exogenous oleate incorporation into phospholipids; and 4) a 2-3-fold decrease in the rates of oleate uptake. These data support the hypothesis that Fat1p is involved in long-chain fatty acid uptake and may represent a long-chain fatty acid transport protein.
Faergeman
N J
NJ
Department of Biochemistry, University of Tennessee College of Medicine, Memphis, Tennessee 38163, USA.
DiRusso
C C
CC
Elberger
A
A
Knudsen
J
J
Black
P N
PN
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001896:Boron Compounds / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002569:Cerulenin / Q000378:metabolism; D050612:Fatty Acid Transport Proteins; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005456:Fluorescent Dyes; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D019301:Oleic Acid / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D002352:Carrier Proteins; C105342:FAT1 protein, S cerevisiae; D050612:Fatty Acid Transport Proteins; D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D002569:Cerulenin; D019301:Oleic Acid