Disruption of the Saccharomyces cerevisiae homologue to the murine fatty acid transport protein impairs uptake and growth on long-chain fatty acids

J Biol Chem. 1997 Mar 28;272(13):8531-8. doi: 10.1074/jbc.272.13.8531.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3T3 Cells
  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism
  • Amino Acid Sequence
  • Animals
  • Boron Compounds / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cerulenin / metabolism
  • Fatty Acid Transport Proteins
  • Fatty Acids, Unsaturated / metabolism
  • Fluorescent Dyes
  • Kinetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Mice
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Oleic Acid / metabolism
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins*

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Carrier Proteins
  • FAT1 protein, S cerevisiae
  • Fatty Acid Transport Proteins
  • Fatty Acids, Unsaturated
  • Fluorescent Dyes
  • Membrane Proteins
  • Membrane Transport Proteins
  • Saccharomyces cerevisiae Proteins
  • Cerulenin
  • Oleic Acid