Pex11p plays a primary role in medium-chain fatty acid oxidation, a process that affects peroxisome number and size in Saccharomyces cerevisiae

The Saccharomyces cerevisiae peroxisomal membrane protein Pex11p has previo usly been implicated in peroxisome proliferation based on morphological obs ervations of PEX11 mutant cells. Pex11p-deficient cells fail to increase pe roxisome number in response to growth on fatty acids and instead accumulate a few giant peroxisomes, We report that mutants deficient in genes require d for medium-chain fatty acid (MCFA) beta-oxidation display the same phenot ype as Pex11p-deficient cells. Upon closer inspection, we found that Pex11p is required for MCFA beta-oxidation. Disruption of the PEX11 gene results in impaired formation of MCFA-CoA esters as measured in intact cells, where as their formation is normal in cell lysates, The sole S. cerevisiae MCFA-C oA synthetase (Faa2p) remains properly localized to the inner leaflet of th e peroxisomal membrane in PEX11 mutant cells. Therefore, the in vivo latenc y of MCFA activation observed in Pex11p-deficient cells suggests that Pex11 p provides Faa2p with substrate. When PEX11 mutant cells are shifted from g lucose to oleate-containing medium, we observed an immediate deficiency in beta-oxidation of MCFAs whereas giant peroxisomes and a failure to increase peroxisome abundance only became apparent much later. Our observations sug gest that the MCFA oxidation pathway regulates the level of a signaling mol ecule that modulates the number of peroxisomal structures in a cell.