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

Abstract

AbstractAlthough 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 ΔPFK1) showed increased glucose consumption, suggesting that redistribution of glucose fluxes between glycolysis and the pentose phosphate shunt is a key regulator of SICD development.