Hungry yeasts are tiny living thermometers

This fluorescence microscopy image shows yeast vacuoles that have undergone phase separation. Credit: Luther Davis / Alexey Merz / University of Washington

Membranes are crucial for our cells. Each cell in your body is surrounded by only one. And each of these cells contains specialized compartments, or organelles, which are also surrounded by membranes.

Membranes help cells perform tasks such as breaking down food for energy, building and breaking down proteins, monitoring environmental conditions, sending signals, and deciding whether to divide.

Biologists have long struggled to understand precisely how membranes perform these different kinds of tasks. The main components of membranes – large fat-like molecules called lipids and compact molecules like cholesterol – are great barriers. In all but a few cases, it’s unclear how these molecules help proteins in membranes do their job.

In an article published on January 25 in the Proceedings of the National Academy of Sciences, a University of Washington team has looked at phase separation in budding yeast – the same single-celled fungus famous for baking and brewing – and reports that living yeast cells can actively regulate a process called phase separation in one of their membranes. During phase separation, the membrane remains intact but divides into several distinct zones or domains that separate lipids and proteins. The new findings show for the first time that in response to environmental conditions, yeast cells precisely regulate the temperature at which their membrane undergoes phase separation. The team behind this discovery suggests that phase separation is likely a “switching” mechanism that these cells use to govern the types of work the membranes do and the signals they send.

“Previous work has shown that these domains can be observed in the membranes of living yeast cells,” said lead author Chantelle LeveilIe, a UW PhD student in chemistry. “We asked: if it’s important for a cell to have these domains, then if we change the environment of the cell – by growing them at different temperatures – will the cell ‘care’? and will it devote energy to maintaining phase separation in its membranes? The clear answer is yes, it does.

Previous research has shown that when sugar is plentiful, the yeast cell’s vacuole – an important organelle for storage and signaling – enlarges and its membrane appears uniform under the microscope. But when the food stores dwindle, the vacuole undergoes phase separation, with many round areas appearing in the membrane of the organelle.

In this new study, Leveille and her co-authors — UW chemistry professor Sarah Keller, UW biochemistry professor Alexey Merz, and Caitlin Cornell, a former UW chemistry doctoral candidate — sought to understand whether yeast can actively regulate phase separation. Léveillé grew yeast at their typical lab temperature of 86 F with plenty of food. After food depletion, the yeast cell vacuole membranes underwent phase separation, as expected. When Léveillé briefly increased the temperature in the yeast environment by about 25 degrees Fahrenheit, the domains disappeared. Next, Léveillé grew the yeast at a cooler temperature — 77 F instead of the normal 86 F — and found that the domains disappeared about 25 degrees above this new temperature. When she grew yeast in even colder conditions, at 68 F, the phase separation again disappeared about 25 degrees above their growth temperature.

These experiments showed that yeast cells still maintained phase separation in the vacuole membrane until the temperature rose to about 25 degrees above their growth temperature.

“We think this is a clear sign that yeast cells manufacture the vacuole membrane under different environmental conditions to maintain this constant state of phase separation,” Leveille said.

Phase separation in the vacuole membrane likely plays an important role in yeast, she added.

“This result suggests that membrane phase separation for yeast is likely a two-way street,” Leveille said. “For example, if the cells found food again, they would want to return to their original state. The yeast doesn’t want to stray too far from the transition.

Future research may identify other membrane components that affect the vacuole membrane’s ability to phase separate, as well as the consequences of its phase separation. Biologists know that when the domains appear in the membrane of the yeast vacuole, the cell stops dividing. These two events may be related because the membrane of the yeast vacuole contains two protein complexes important for cell division. When the complexes are pulled apart, cell division stops.

“Phase separation in the vacuole occurs just when the yeast cell needs to stop dividing because its food supply has run out, Merz said. “One idea is that phase separation is the mechanism that the yeast cell ‘uses’ to separate these two protein complexes and stop cell division.”

In cells from yeast to human, protein complexes embedded in membranes affect cellular behavior. If further research shows that phase separation in the yeast vacuole regulates cell division, this would likely be the first rigorous example of cellular regulation by this once overlooked property of membranes.

“Phase separation could be a common and reversible mechanism for modulating very many types of cellular properties,” Keller said.

Cornell is now a postdoctoral fellow at the University of California, Berkeley.

Living cell membranes can self-sort their components by “unmixing” them

More information:

Chantelle L. Leveille et al, yeast cells actively regulate their membranes to phase separate at temperatures that change with growth temperatures, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2116007119

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Hungry yeasts are tiny living thermometers (2022, January 25)
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