Is Aggregate-Dependent Yeast Aging Fortuitous? A Model of Damage Segregation and Aggregate Dynamics

Abstract

During cytokinesis in Saccharomyces cerevisiae, damaged proteins are distributed unequally between the daughter and mother cells. The retention of these proteins is correlated with yeast aging. Even though evidence suggests that aggregates are retained due to an underlying molecular mechanism, the debate on whether an active mechanism is necessary for this asymmetry remains unsolved. In particular, passive diffusion and a bud-specific dilution remain as possible explanations. Here, a computational and mathematical model is provided to test whether passive mechanisms alone are sufficient to account for the aggregate distribution patterns and the aggregate kinetics observed in living cells. To this author’s knowledge, this is the most comprehensive model available on this subject and the only one combining key potentially essential passive-only mechanisms proposed in existing bibliography—namely, the geometrical effect of the dividing yeast cell on the diffusion of protein aggregates, and the possibility of aggregate binding and aggregate formation at different rates. Results suggest that although passive processes alone can reproduce certain averaged observables from experimental bibliography, they are insufficient to vindicate aggregate activity observed in living budding yeast cells. These results are complemented by showing that under basic forms of active quality control, discrepancies between the outputs of the model and experimental bibliography are reduced.