Protein Aggregation in Unicellular Eukaryotes

This chapter describes how unicellular eukaryotic cells, especially the budding yeast S. cerevisiae, deal with the presence of misfolded protein, beginning with their detection [in the endoplamic reticulum (ER), cytosol, or nucleus], their attempted refolding, and eventually, their degradation (proteasome or autophagy). It presents examples of proteins that naturally assume amyloid-like structures, and provides an overview of validated humanized yeast models. The accumulation of unfolded or misfolded proteins in the ER leads to ER stress and activation of the unfolded protein response (UPR). Disease-like amyloidogenic proteins were found to accumulate primarily within the IPOD, and not in a JUNQ. In addition to the research on protein aggregation in higher eukaryotic organisms, the study of protein misfolding in eukaryotic unicellular model organisms has been highly instructive in understanding the molecular mechanisms driving the cellular buildup of protein aggregates.