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

Abstract

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.