FIGURE 11.

αSyn clearance and degradation in yeast. Proteasome and autophagy/vacuole as major degradation pathways are depicted. When synthesis of αSyn is switched off, wild-type yeast cells clear αSyn aggregates within hours and regain normal growth rates (38). In the presence of functional SUMO, the aggregates are primarily cleared by the autophagy/vacuolar pathway. When sumoylation is impaired, the aggregate clearance through autophagy/vacuolar pathway is prevented, and the proteasomal degradation is promoted. Increase of Ser-129 phosphorylation level by GRK5 or PLK2 rescues the autophagic aggregate clearance and additionally promotes the proteasomal degradation. For monomers, degradation of soluble αSyn monomers occurs through both pathways. Inhibition of αSyn sumoylation has a strong effect on monomer protein stability, significantly increasing the half-life of the protein and inhibiting the degradation through both pathways. Phosphorylation at Ser-129 by GRK5 or PLK2 decreases the protein stability and promotes degradation of soluble αSyn through proteasome and autophagy pathways.