A prolonged chronological lifespan is an unexpected benefit of the [PSI+] prion in yeast

Abstract

Self-replicating ‘proteinaceous infectious particles’ or prions are responsible for complex heritable traits in the yeast Saccharomyces cerevisiae. Our current understanding of the biology of yeast prions stems from studies mostly done in the context of actively dividing cells in optimal laboratory growth conditions. Evidence suggest that fungal prions exist in the wild where most cells are in a non-dividing quiescent state, because of imperfect growth conditions, scarcity of nutrients and competition. We know little about the faithful transmission of yeast prions in such conditions and their physiological consequences throughout the lifespan of yeast cells. We addressed this issue for the [PSI+] prion that results from the self-assembly of the translation release factor Sup35p into insoluble fibrillar aggregates. [PSI+] leads to increased nonsense suppression and confers phenotypic plasticity in response to environmental fluctuations. Here, we report that while [PSI+] had little to no effect on growth per se, it dramatically improved the survival of yeast cells in stationary phase. Remarkably, prolonged chronological lifespan persisted even after [PSI+] was cured from the cells, suggesting that prions may facilitate the acquisition of complex new traits. Such an important selective advantage may contribute to the evolutionary conservation of the prion-forming ability of Sup35p orthologues in distantly related yeast species.

Growth phase‐dependent changes in the size and infectivity of SDS‐resistant Sup35p assemblies associated with the [PSI+] prion in yeast

“…). In these conditions, the post‐diauxic shift growth lasts longer ((Wang et al , ) and data not shown). This may partly account for the differences observed in Sup35p levels at day 7 between the two types of experiments (Figs B and D).…”

“…To gain further insight into this finding, [ psi ‐ ] and weak ([ PSI + ] W ) or strong ([ PSI + ] S ) [ PSI + ] derivatives of the 74‐D694 yeast strain were cultivated in rich YPDA medium. Cultures were started by inoculating exponentially growing cells into fresh medium (Wang et al , ), and aliquots were then taken at different time intervals for analysis (Fig. ).…”

“…depend on cell lysate preparation, we sought alternative cell breakage methods that would preserve the integrity of protein complexes while limiting proteolysis. We turned to liquid nitrogen grinding as the method of choice to prepare cell lysates from equal numbers of [ psi ‐ ], [ PSI + ] S and [ PSI + ] W cells harvested in the exponential (0.3 days), post‐diauxic shift (day 2) or early stationary phases (day 7) of growth (see Experimental procedures) (Wang et al , ). The protein concentrations within [ psi ‐ ], [ PSI + ] S and [ PSI + ] W cell lysates were similar for each growth phase (Fig.…”

“…Solid media contained 2% bacto‐agar. Yeast cultures were all started with exponentially growing cells as described (Wang et al , ). Prion phenotypes were monitored on ¼‐YPD medium (0.25% yeast extract, 2% peptones, 2% glucose) via a standard color‐based phenotype assay, as described before (Kabani et al , ; ).…”

“…To which extent the [PSI + ] variants affect the proteome is however still unclear (Baudin-Baillieu et al, 2014;Chan et al, 2017). [PSI + ] has been shown to facilitate the phenotypic manifestation of hidden genetic variation (True and Lindquist, 2000;True et al, 2004;Tyedmers et al, 2008;Halfmann et al, 2012), and we and others have recently showed that [PSI + ] cells have a longer chronological lifespan (Speldewinde and Grant, 2017;Wang et al, 2017).…”