The Effect of Calorie Restriction on Protein Quality Control in Yeast

Initially, protein aggregates were regarded as a sign of a pathological state of the cell. Later, it was found that these assemblies are formed in response to stress, and that some of them serve as signalling mechanisms. This review has a particular focus on how intracellular protein aggregates are related to altered metabolism caused by different glucose concentrations in the extracellular environment. We summarise the current knowledge of the role of energy homeostasis signalling pathways in the consequent effect on intracellular protein aggregate accumulation and removal. This covers regulation at different levels, including elevated protein degradation and proteasome activity mediated by the Hxk2 protein, the enhanced ubiquitination of aberrant proteins through Torc1/Sch9 and Msn2/Whi2, and the activation of autophagy mediated through ATG genes. Finally, certain proteins form reversible biomolecular aggregates in response to stress and reduced glucose levels, which are used as a signalling mechanism in the cell, controlling major primary energy pathways related to glucose sensing.