A glucose-starvation response regulates the diffusion of macromolecules

Abstract

The organization and biophysical properties of the cytosol implicitly govern molecular interactions within cells. However, little is known about mechanisms by which cells regulate cytosolic properties and intracellular diffusion rates. Here, we demonstrate that the intracellular environment of budding yeast undertakes a startling transition upon glucose starvation in which macromolecular mobility is dramatically restricted, reducing the movement of both chromatin in the nucleus and mRNPs in the cytoplasm. This confinement cannot be explained by an ATP decrease or the physiological drop in intracellular pH. Rather, our results suggest that the regulation of diffusional mobility is induced by a reduction in cell volume and subsequent increase in molecular crowding which severely alters the biophysical properties of the intracellular environment. A similar response can be observed in fission yeast and bacteria. This reveals a novel mechanism by which cells globally alter their properties to establish a unique homeostasis during starvation.DOI: http://dx.doi.org/10.7554/eLife.09376.001

Design and Properties of Genetically Encoded Probes for Sensing Macromolecular Crowding

“…If, for example, higher crowded regions (due to an increased affinity between the cytosolic proteins, possibly combined with size sorting by the depletion interaction) or regions with only smaller crowders exist (48,49), it may induce inhomogeneous distribution of the sensor to the less crowded regions. Inhomogeneous distribution could potentially occur under, for example, starvation conditions, or when other stresses are imposed on the cell (50)(51)(52). In these cases, the probes may indicate changes in the superstructure of the cytoplasm, especially when combined with classical volume fraction determinations from cell dry weight and probe diffusion measurements (17,44).…”

Cytoplasmic RNA-Protein Particles Exhibit Non-Gaussian Subdiffusive Behavior

“…Examples include az0:7 for RNA-protein particles in E. coli (14,21) and S. cerevisiae (22), az0:7 for lipid granules in fission yeast (23), az0:5 for gold nanoparticles in several human and mammalian cell lines (24), and az0:5 À 0:8 for dextrans in HeLa cells (25). Chromosomal loci also exhibit subdiffusive behavior, with az0:4 À 0:5 for E. coli (26,27), az0:5 À 0:7 in budding yeast (28,29), and az0:3 for mammalian telomeres at timescales <10 s (30).…”

Similar environments but diverse fates: Responses of budding yeast to nutrient deprivation

“…Quiescence is a differentiated state in which yeast cease growth (reviewed in 12) and undergo genome-wide changes in transcriptional expression and chromosome topography 787980, cytoskeletal organization 81 and cytosolic fluidity 8283. Thus, like sporulation, quiescence is a response to nutrient deprivation that is likely to require an energy investment.…”