Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants (DenseTimeCourse)

Here we sought to comprehensively characterize the role of the electron transport chain in yeast models of aging. Using a panel of ETC mutants, we observed that ETC mutants fail to survive starvation when grown to saturation in standard SD growth medium. This starvation lethality is associated with a significantly lower cytosolic pH and dysregulated gene expression compared to wild type cells. In an unbiased genetic suppressor screen, we found that loss of function mutations in major cellular nutrient sensing/signaling pathways (Ras/PKA, Tor, PP2A) along with a number of gene expression regulators can prevent starvation lethality in these mutants. Together our results suggest that the ETC plays a critical regulatory role in mounting an appropriate response to starvation through communication with major nutrient sensing/signaling pathways in the cell.