Journal Article

A pH-driven transition of the cytoplasm from a fluid- to a solid-like state promotes entry into dormancy

Midtvedt, Daniel, Ulbricht, Elke, Taubenberger, Anna, Zaburdaev, Vasily, Herbig, Maik, Malinovska, Liliana, Guck, Jochen, Franzmann, Titus, Richter, Doris, Nüske, Elisabeth, Otto, Oliver, Maharana, Shovamayee, Müller, Paul, Alberti, Simon, Munder, Matthias Christoph

2016

Overview

Cells can enter into a dormant state when faced with unfavorable conditions. However, how cells enter into and recover from this state is still poorly understood. Here, we study dormancy in different eukaryotic organisms and find it to be associated with a significant decrease in the mobility of organelles and foreign tracer particles. We show that this reduced mobility is caused by an influx of protons and a marked acidification of the cytoplasm, which leads to widespread macromolecular assembly of proteins and triggers a transition of the cytoplasm to a solid-like state with increased mechanical stability. We further demonstrate that this transition is required for cellular survival under conditions of starvation. Our findings have broad implications for understanding alternative physiological states, such as quiescence and dormancy, and create a new view of the cytoplasm as an adaptable fluid that can reversibly transition into a protective solid-like state. Most organisms live in unpredictable environments, which can often lead to nutrient shortages and other conditions that limit their ability to grow. To survive in these harsh conditions, many organisms adopt a dormant state in which their metabolism slows down to conserve vital energy. When the environmental conditions improve, the organisms can return to their normal state and continue to grow. The interior of cells is known as the cytoplasm. It is very crowded and contains many molecules and compartments called organelles that carry out a variety of vital processes. The cytoplasm has long been considered to be fluid-like in nature, but recent evidence suggests that in bacterial cells it can solidify to resemble a soft glass-type material under certain conditions. When cells become dormant they stop dividing and reorganise their cytoplasm in several ways; for example, the water content drops and many essential proteins form storage compartments. However, it was not clear how cells regulate the structure of the cytoplasm to enter into or exit from dormancy. Now, Munder et al. analyse the changes that occur in the cytoplasm when baker’s yeast cells enter a dormant state. The experiments show that when yeast cells are deprived of energy – as happens during dormancy – the cytoplasm becomes more acidic than normal. This limits the ability of molecules and organelles to move around the cytoplasm. Similar results were also seen in other types of fungi and an amoeba. Munder et al. found that this increase in acidity during dormancy causes many proteins to interact with each other and form large clumps or filament structures that result in the cytoplasm becoming stiffer. A separate study by Joyner et al. found that when yeast cells are starved of sugar, two large molecules are less able to move around the cell interior. Together, the findings of the studies suggest that the interior of cells can undergo a transition from a fluid-like to a more solid-like state to protect the cells from damage when energy is in short supply. The next challenge is to understand the molecular mechanisms that cause the physical properties of the cytoplasm to change under different conditions.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Acidification / Biophysics and Structural Biology / Cell Biology / Cell cycle / Cell Survival / Cytoplasm / Cytoplasm - chemistry / Cytoplasm - drug effects / cytosolic pH / Dictyostelium - physiology / Dormancy / Energy / Enzymes / Hydrogen-Ion Concentration / macromolecular assembly / Macromolecules / Metabolism / Mobility / Organelles / pH effects / phase transition / Phase Transition - drug effects / Proteins / Protons / Saccharomyces cerevisiae - physiology / Starvation / Stress, Physiological