Sugar-induced Cell Death (SICD) in Saccharomyces Cerevisiae: Insights into Nitrogen-Mediated Rescue and Apoptotic Cell Death Pathways

Sugar-induced cell death (SICD) is a phenomenon observed in Saccharomyces cerevisiae whereby cells rapidly lose viability in glucose-only solutions. One theory suggests that SICD occurs due to an imbalance in nitrogen and carbon, however, limited studies are available to support this. When stationary phase cells are transferred to glucose-only solutions, cell death resembles that of apoptosis, while exponential phase cells show hallmarks of primary necrosis. Apoptosis in stationary phase cells is independent of the yeast metacaspase, YCA1, however, it remains unknown if SICD occurs through a caspase-independent pathway. Using stationary phase S. cerevisiae BY4741, we showed that SICD can be induced to the same degree with 10 mM or 110 mM glucose. Interestingly, SICD induced by 10 mM of glucose can be protected by supplementation with low concentrations of highly preferred organic nitrogen sources, namely glutamate, glutamine, and arginine, as well as high concentrations of non-preferred organic nitrogen sources. Additionally, cell death can be rescued by deletion of YCA1 and genes involved in caspase-independent apoptosis—STE20, NMA111, AIF1, or NUC1. On the other hand, when S. cerevisiae BY4741 is challenged with 110 mM glucose, SICD can only be rescued by supplementation with the same preferred organic nitrogen sources or deletion of AIF1 or NMA111. In all cases, protection is associated with a decrease in intracellular ROS and preservation of membrane integrity. Taken together, 110 mM glucose results in a catastrophic cell death phenotype that is more difficult to rescue, and nuclear localization of Aif1p and Nma111p is important for cell death in response to glucose.