Peters et al. describe how starving yeast cells regulate the formation of proteasome storage granules (PSGs).
The proteasome is a large, multisubunit protease essential for many cellular functions including proliferation. In the absence of glucose or other carbon sources, budding yeast aggregate their proteasomes in PSGs, which may help protect the complexes until conditions improve. When glucose becomes available again, PSGs disperse, allowing cells to quickly reenter the cell cycle without waiting for new proteasomes to be built from scratch. How glucose levels regulate PSG assembly is unclear, however.
By screening a library of yeast deletion mutants, Peters et al. found that yeast lacking components of the vacuolar ATPase (V-ATPase) formed PSGs more quickly upon glucose starvation but took longer to disassemble the granules when glucose supplies were restored. The V-ATPase pumps protons out of the cytosol and into the vacuole, so yeast lacking this complex have a lower cytoplasmic pH. Lowering intracellular pH in other ways—by mutating the plasma membrane proton pump Pma1, for example—also promoted PSG formation, even in the presence of normal glucose levels. Low pH also stimulated the assembly of other cytoplasmic granules, such as actin bodies, that form in starving yeast cells.
Glucose deprivation is known to induce disassembly of the V-ATPase, which would acidify the cytosol and stimulate PSG formation. Senior author Shay Ben-Aroya now wants to determine how low pH promotes PSG assembly and to investigate whether proteasomes are inactive inside PSGs or whether they continue to degrade proteins during cell starvation.
Text by Ben Short