Cell cycle-linked vacuolar pH dynamics regulate amino acid homeostasis and cell growth

Amino acid homeostasis is critical for many cellular processes. It is well established that amino acids are compartmentalized using pH gradients generated between organelles and the cytoplasm; however, the dynamics of this partitioning has not been explored. Here we develop a highly sensitive pH reporter and find that the major amino acid storage compartment in Saccharomyces cerevisiae, the lysosome-like vacuole, alkalinizes before cell division and re-acidifies as cells divide. The vacuolar pH dynamics require the uptake of extracellular amino acids and activity of TORC1, the v-ATPase and the cycling of the vacuolar specific lipid phosphatidylinositol 3,5-bisphosphate, which is regulated by the cyclin-dependent kinase Pho85 (CDK5 in mammals). Vacuolar pH regulation enables amino acid sequestration and mobilization from the organelle, which is important for mitochondrial function, ribosome homeostasis and cell size control. Collectively, our data provide a new paradigm for the use of dynamic pH-dependent amino acid compartmentalization during cell growth/division. In this study, Okreglak et al. identify dynamic regulation of pH in the lysosome-like vacuole of growing S. cerevisiae cells and link pH dynamics in this subcellular compartment to amino acid release into the cytoplasm to meet metabolic demands during cell cycle progression.

Automated summary

This study reveals that the lysosome-like vacuole in Saccharomyces cerevisiae undergoes dynamic pH regulation, with alkalinization before cell division and re-acidification during cell division. This pH regulation is critical for amino acid storage and mobilization, which are important for various cellular processes.