Phosphoinositide-3-Kinase Vps34p is required for peroxisomal degradation in the yeast Saccharomyces cerevisiae

Many organelles in eukaryotic cells are exposed to a high variation concerning their protein composition and number. To adjust the required amount of organelles to the environmental conditions, both the biogenesis and degradation of theses organelles underlie highly regulated control mechanisms. The specific degradation of peroxisomes is called pexophagy, a process which is inducible in S. cerevisiae by a shift from peroxisome inducing conditions to glucose- rich media. Some evidence exists that the membrane is marked for degradation by Phosphatidylinositolphosphates, phosphorylated derivatives of the membrane phospholipid phosphatidylinositol (PtdIns).

Here we identify phosphatidylinositolphosphate synthesizing activity in purified peroxisomal membranes with radioactive labeled ATP and demonstrate by means of subcellular fractionation that the lipid kinase Vps34p, which is a vacuolar protein responsible for protein sorting, is associated with peroxisomes. Peroxisome biogenesis, analyzed with density gradient centrifugation and fluorescence microscopy, is not affected in vps34Δ cells. However, our work proved that Vps34p is essential for the regulated degradation of peroxisomes. The reduced steady state protein concentration of oleic acid inducible proteins in vps34D cells is due to the slower growth rate of the deletion strain. Overexpression of the PtdIns3P binding domain FYVE shows that Vps34p regulates the pexophagy via the PtdIns3P effector proteins.