Identification of peroxisomal acyl-CoA thioesterases in yeast and humans

A computer-based screen of the Saccharomyces cerevisiae genome identified Y JR019C as a candidate oleate-induced gene. YJR019C mRNA levels were increas ed significantly during growth on fatty acids, suggesting that; it may play a role in fatty acid metabolism, The YJR019C product is highly similar to tesB, a bacterial acyl-CoA thioesterase, and carries a tripeptide sequence, alanine-lysine-phenylalanine(COOH), that closely resembles the consensus s equence for type-1 peroxisomal targeting signals. YJR019C directed green fl uorescence protein to peroxisomes, and biochemical studies revealed that YJ R019C is an abundant component of purified yeast peroxisomes, Disruption of the YJR019C gene caused a significant decrease in total cellular thioester ase activity, and recombinant YJR019C was found to exhibit intrinsic acyl-C oA thioesterase activity of 6 units/mg, YJR019C also shared significant seq uence similarity with hTE, a human thioesterase that was previously identif ied because of its interaction with human immunodeficiency virus-Nef in the yeast two-hybrid assay. We report here that hTE is also a peroxisomal prot ein, demonstrating that thioesterase activity is a conserved feature of per oxisomes, We propose that YJR019C and hTE be renamed as yeast, and human PT E1 to reflect the fact that they encode peroxisomal thioesterases. The phys ical segregation of yeast and human PTE1 from the cytosolic fatty acid synt hase suggests that these enzymes are unlikely to play a role in formation o f fatty acids. Instead, the observation that PTE1 contributes to growth on fatty acids implicates this thioesterase in fatty acid oxidation.