Eukaryotic cells form cytoplasmic RNA-protein aggregates or stress granules (SGs) under a variety of stress conditions and their formation is associated with both neurodegenerative diseases and cancer. For each stress condition distinct stress-activated signaling pathways regulate SG formation, however the molecular details of these pathways remain largely unknown. We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for SG formation specifically upon glucose deprivation but no other stresses tested. Similarly the Tip60 complex, the human homolog of the yeast NuA4 complex, is also required for SG formation in human cell lines indicating that NuA4/Tip60 is a conserved signaling pathway regulating SG dynamics. Surprisingly we found that the impact of NuA4 on glucose-deprived SG formation is not through the regulation of core SG protein levels, or inhibition of translation, rather it is through regulation of acetyl-CoA levels. Cells in which the Acetyl-CoA synthetase ACS1 is deleted, which have decreased acetyl-CoA levels, display increased SG formation upon glucose deprivation. In agreement, cells in which the Acetyl-CoA carboxylase ACC1 is mutated or in cells exogenous treated with acetate, which have increased acetyl-CoA levels, glucose deprived SG formation is suppressed. Like NuA4, acetyl-CoA levels appear to only contribute to SG formation upon glucose deprivation. Remarkably we determined that mutants of NuA4 have increased acetyl-CoA levels, decreased Acc1 activity and mislocalized Acc1-GFP. Our observations indicate that NuA4 is regulating acetyl-CoA levels through Acc1 and that acetyl-CoA is acting as a signaling rheostat for SG formation upon glucose deprivation.