Electron transport chain disruption leads to failure of glucose derepression via the Snf1/AMPK pathway

When Saccharomyces cerevisiae cells transition from a glucose-rich environment to low glucose conditions, the expression of genes that were previously repressed by glucose is derepressed, enabling the cell to adapt metabolic processes to the available carbon source. The Snf1 pathway is one of the primary signaling pathways responsible for orchestrating glucose sensing and signaling. In this study, we investigate the impact of disrupted electron transport chain (ETC) function, a mitochondrial protein complex essential for respiratory energy generation, in glucose derepression. We observe that respiratory incompetent mutants exposed to glucose are unable to subsequently utilize galactose as a carbon source in minimal media. In contrast, ETC mutants that have been generated and maintained on galactose can effectively continue to metabolize galactose until glucose exposure. We define this phenomenon as a Failure of Glucose Derepression (FGD), wherein respiratory incompetent cells fail to fully reverse glucose repressed gene expression regulation. Through further characterization, we show how irregular localization patterns of crucial proteins within the Snf1 pathway are associated with FGD suggesting a potential novel connection between the ETC and the Snf1 pathway during carbon source transition. SIGNIFICANCE STATEMENTO_LIRespiratory incompetent electron-transport chain mutants are capable of metabolizing galactose as a carbon source. However, when ETC mutants encounter glucose, they lose this ability to metabolize galactose. C_LIO_LIThis study demonstrates that failure to derepress glucose repressed genes facilitated by the Snf1/AMPK pathway is primarily responsible for this phenotype in ETC mutants. C_LIO_LIThese results illustrate a novel signaling role for the ETC and suggest a possible metabolic intervention to certain disease phenotypes. C_LI