Reorganization of budding yeast cytoplasm upon energy depletion

Abstract

Yeast cells, when exposed to stress, can enter a protective state in which cell division, growth and metabolism are downregulated. They remain viable in this state until nutrients become available again. How cells enter this protective survival state and what happens at a cellular and subcellular level is largely unknown. In this study, we used electron tomography to investigate the stress-induced ultrastructural changes in the cytoplasm of yeast cells. After ATP depletion, we observed a significant cytosolic compaction and an extensive cytoplasmic reorganization, as well as the emergence of distinct membrane-bound and membrane-less organelles. By using correlative light and electron microscopy (CLEM), we further demonstrate that one of these membrane-less organelles is generated by the reversible polymerization into large bundles of filaments of the eukaryotic translation initiation factor 2B (eIF2B), an essential enzyme in the initiation of protein synthesis. The changes we observe are part of a stressinduced survival strategy, allowing yeast cells to save energy, protect proteins from degradation, and inhibit protein functionality by forming assemblies of said proteins.

Membrane and lipid metabolism plays an important role in desiccation resistance in the yeast Saccharomyces cerevisiae

“…As a result, stationary cells have more LDs than log-phase dividing cells. A recent report showed that the number of LDs increased even when yeast cells were given a short period of glucose starvation by replacing glucose with a non-hydrolysable glucose analogue [ 46 ]. At stationary phase, fatty acids are released slowly from triglycerides and degraded via β-oxidation, to provide energy necessary for cellular maintenance [ 41 ].…”

Nuclear pores constrict upon energy depletion

“…This points to a well conserved mechanism, likely dependent on a concomitantly reduced availability of free GTP (27). Moreover, energy depletion (ED) leads to a general reorganization of the cytoplasm including solidification of the periplasm, general water loss and reduction of the nuclear and cellular volume, which allows cells to endure under unfavorable conditions (28)(29)(30)(31). If the shutdown of active nuclear transport coincides with the alteration in passive diffusion and potentially a conformational adaption of NPC architecture remains unknown.…”

Structural insights into ISRIB, a memory‐enhancing inhibitor of the integrated stress response

“…Intriguingly, the yeast eIF2B forms polymers under conditions of stress in vivo [25][26][27][28]. These latter data raise the possibility that eIF2B may bind nucleotides or sugars that regulate its function.…”