Valiakhmetov, A. | Search bioRxiv

bioRxiv2024

Suppression of glycolysis decreases sugar-induced cell death in Saccharomyces cerevisiae.

Although 30 years have passed since the description of sugar-induced cell death (SICD), the specific molecular mechanism that triggers this process remains unclear. This paper attempts to shed light on the relationship between SICD and glucose catabolism. Deletion of the TPS1 gene resulted in a 44% suppression of SICD and a 75% reduction in the number of cells with excess ROS. The suppression was comparable to the suppression of SICD (38%) and ROS (71%) with deletion of the HXK2 gene. Since HXK2 is the first enzyme in the glycolytic pathway, the effect of two other key glycolytic enzymes on SICD was tested. Deletion of the TDH3 gene (glyceraldehyde-3-phosphate dehydrogenase) resulted in a 39% suppression of SICD and ROS by 48%. Inhibition of Tdh3p with 1 mM iodoacetamide also suppressed SICD by 67% and ROS by 58%. Deletion of the PFK1 (phosphofructokinase 1) gene resulted in a complete block of SICD (97%), but unexpectedly resulted in a significant increase in the number of cells with excess ROS. All strains tested (except {Delta}PFK1) showed increased glucose consumption, suggesting that redistribution of glucose fluxes between glycolysis and the pentose phosphate shunt is a key regulator of SICD development.

biochemistry↗

bioRxiv2023

Analysis of sugar-induced cell death dynamics in S. cerevisiae strains with deleted genes involved in several key metabolic processes.

Backgroundincubation of exponentially growing yeast S.cerevisiae with glucose in the absence of other nutrients results in Sugar Induced Cell Death (SICD). SICD is accompanied by the accumulation of reactive oxygen species (ROS), has the nature of primary necrosis, affects cells in the S-phase of the cell cycle, and is completely suppressed by dissipation of {Delta}{Psi}. The specific mechanism linking the {Delta}{Psi} status to the induction of SICD remains unclear. This study aimed to attempt to identify the specific molecular mechanism responsible for ROS overproduction and the development of SICD. MethodsThe main method employed was the analysis of SICD development in a set of knockout mutants targeting key participants in metabolic processes. ResultsA statistically significant decrease in the number of cells with ROS overproduction was observed in the {Delta}AFO1, {Delta}POX1, {Delta}YNO1, {Delta}TRK1, {Delta}TRK2, {Delta}VSB1, and {Delta}YPR003C strains. A significant decrease in the number of cells with SICD was shown in the {Delta}TRK1, {Delta}VSB1, and {Delta}YPR003C strains. The development of SICD is not due to the presence of a nitrogen reactive species (NRS). Deletion of certain genes expressed during the S-phase of the cell cycle did not alter the dynamics of ROS accumulation and the development of SICD. The presence of exogenous or endogenous glutathione significantly suppresses both processes studied, although not as effectively as {Delta}{Psi} dissipation. ConclusionsThe development of SICD is dependent on the presence of ROS, but is not strictly linked to it, as evidenced by the effects of glutathione and mutations related to its biosynthesis. In all strains tested, SICD was critically dependent on {Delta}{Psi}, although the nature of its generator remains unclear.

biochemistry↗