DISRUPTION OF THE SACCHAROMYCES-CEREVISIAE HOMOLOG 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, ph ospholipid biosynthesis, and protein modification, The molecular mecha nisms that govern the uptake of these compounds in S. cerevisiae have not been described, We report the characterization of FAT1, a gene tha t encodes a putative membrane-bound long-chain fatty acid transport pr otein (Fat1p). Fat1p contains 623 amino acid residues that are 33% ide ntical and 54% with similar chemical properties as compared with the f atty acid transport protein FATP described in 3T3-L1 adipocytes (Schaf fer and Lodish (1994) Cell 79, 427-436), suggesting a similar function . Disruption of FAT1 results in 1) an impaired growth in YPD medium co ntaining 25 mu M cerulenin and 500 mu M fatty acid (myristate (C-14:0) , palmitate (C-16:0), or oleate (C-18:1)); 2) a marked decrease in the uptake of the fluorescent long-chain fatty acid analogue boron dipyrr omethene difluoride dodecanoic acid (BODIPY-3823); 3) a reduced rate o f exogenous oleate incorporation into phospholipids; and 4) a 2-3-fold decrease in the rates of oleate uptake, These data support the hypoth esis that Fat1p is involved in long-chain fatty acid uptake and may re present a long-chain fatty acid transport protein.