Identification of a peroxisomal ATP carrier required for medium-chain fatty acid beta-oxidation and normal peroxisome proliferation in Saccharomyces cerevisiae

We have characterized the role of YPR128cp, the orthologue of human PMP34, in fatty acid metabolism and peroxisomal proliferation in Saccharomyces cer evisiae. YPR128cp belongs to the mitochondrial carrier family (MCF) of solu te transporters and is localized in the peroxisomal membrane. Disruption of the YPR128c gene results in impaired growth of the yeast with the medium-c hain fatty acid (MCFA) laurate as a single carbon source, whereas normal gr owth was observed with the long-chain fatty acid (LCFA) oleate. MCFA but no t LCFA beta -oxidation activity was markedly reduced in intact ypr128c Delt a mutant cells compared to intact wild-type cells, but comparable activitie s were found in the corresponding lysates. These results imply that a trans port step specific for MCFA beta -oxidation is impaired in ypr128c Delta ce lls. Since MCFA beta -oxidation in peroxisomes requires both ATP and CoASH for activation of the MCFAs into their corresponding coenzyme A esters, we studied whether YPR128cp is an ATP carrier. For this purpose we have used f irefly luciferase targeted to peroxisomes to measure ATP consumption inside peroxisomes. We show that peroxisomal luciferase activity was strongly red uced in intact ypr128c Delta mutant cells compared to wild-type cells but c omparable in lysates of both cell strains. We conclude that YPR128cp most l ikely mediates the transport of ATP across the peroxisomal membrane.