The Effect of Lithium on the Budding Yeast Saccharomyces cerevisiae upon Stress Adaptation

Abstract

Lithium salts are used in the treatment of mood disorders, cancer, and Alzheimer’s disease. It has been shown to prolong life span in several phyla; however, not yet in budding yeast. In our study, we investigate the influence of lithium on yeast cells’ viability by characterizing protein aggregate formation, cell volume, and molecular crowding in the context of stress adaptation. While our data suggest a concentration-dependent growth inhibition caused by LiCl, we show an extended long-term survival rate as an effect of lithium addition upon glucose deprivation. We show that caloric restriction mitigates the negative impact of LiCl on cellular survival. Therefore, we suggest that lithium could affect glucose metabolism upon caloric restriction, which could explain the extended long-term survival observed in our study. We find furthermore that lithium chloride did not affect an immediate salt-induced Hsp104-dependent aggregate formation but cellular adaptation to H2O2 and acute glucose starvation. We presume that different salt types and concentrations interfere with effective Hsp104 recruitment or its ATP-dependent disaggregase activity as a response to salt stress. This work provides novel details of Li+ effect on live eukaryotic cells which may also be applicable in further research on the treatment of cancer, Alzheimer’s, or other age-related diseases in humans.

The Effect of Calorie Restriction on Protein Quality Control in Yeast

“…Nonetheless, a two-hour pre-adaptation to LiCl or NaCl resulted in fewer cells with aggregates upon glucose starvation. It was also shown that glucose limitation mitigates the negative effects of LiCl on cell survival, suggesting that adaptation to low glucose conditions is related to other stress pre-adaptations [16]. This is consistent with the fact that CR induces mild stress in the cell, as the levels of ROS are increased through the inactivation of catalase activity [35].…”

“…Since then, yeast has become an invaluable model system to study pathological conditions and ageing, including through the expression of human proteins involved in neurodegenerative disorders, such as Alzheimer's, Parkinson's and Huntington's diseases [2][3][4]. The budding yeast Saccharomyces cerevisiae has been widely used in studies of how different nutritional environments affect proteostasis and the relationship between glucose metabolism and the accumulation of misfolded proteins [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. In this review, we summarise the current knowledge on the connection between protein aggregation and the depletion of glucose and how it is controlled through glucose signalling pathways.…”

“…A low glucose environment has been linked to the accumulation of misfolded proteins in yeast, as it invokes a stress response [15,16]. A low glucose concentration in the yeast medium has been accepted as a calorie restriction (CR) condition [34].…”

“…Using single-cell fluorescent microscopy, it has been shown that glucose starvation elevates the number of yeast cells with Hsp104-bound aggregates within 90 min of low glucose exposure [16]. This is an indication that such conditions moderately increase the protein aggregation rate.…”

iPAR: a new reporter for eukaryotic cytoplasmic protein aggregation

“…On the right, jitter plot of the intensity measured in each fluorescent focus identified. Outlier detection and removal was performed using standard interquartile methods (83, 84). C) Fluorescence micrographs of dual label strain for simultaneous observation of aggregates and key cellular compartments.…”