Saccharomyces cerevisiae Pex3p and Pex19p are required for proper localization and stability of peroxisomal membrane proteins

The mechanisms by which peroxisomal membrane proteins (PMPs) are targeted t o and inserted into membranes are unknown, as are the required components. We show that among a collection of 16 Saccharomyces cerevisiae peroxisome b iogenesis (pex) mutants, two mutants,pex3 Delta and pex19 Delta, completely lack detectable peroxisomal membrane structures and mislocalize their PMPs to the cytosol where they are rapidly degraded. The other pex Delta mutant s contain membrane structures that are properly inherited during vegetative growth and that house multiple PMPs, Even Pex15p requires Pex3p and Pex19p for localization to peroxisomal membranes. This PMP was previously hypothe sized to travel via the endoplasmic reticulum (ER) to peroxisomes, We provi de evidence that ER-accumulated Pex15p is not a sorting intermediate on its way to peroxisomes, Our results show that Pex3p and Pex19p are required fo r the proper localization of all PMPs tested, including Pex15p, whereas the other Per proteins might only be required for targeting/import of matrix p roteins.