Acidic media favor entry of yeast into quiescence

From the Tsukiyama lab, Basic Sciences Division

They live in bread dough. They die in your oven.

In the grocery store, where you buy them, they stand in small glass jars, dormant, waiting to be rehydrated so they can eat sugar and form bubbles in your bread.

We are talking about baker's yeast or as we, scientists, know it Saccharomyces cerevisiae.

As it turns out, baker’s yeast is very famous in research to study a variety of biological processes such as quiescence- a state in which cells do not divide but are metabolically active and can re-enter the cell cycle with the proper stimuli.  Yeast are eukaryotes, just like people, and many processes and functions are conserved between the two distantly related species.

Research on quiescence can be challenging, since a number of factors can influence whether or not cells enter quiescence. For example, changes in the acidity of the media in which cells are cultured, temperature or cell density.

The latest publication by Dr. Toshio Tsukiyama, a professor in the Basic Sciences Division, and led by Alison Greenlaw, a former graduate student in the UW MCB graduate program, investigated whether media pH affects yeast quiescence entry efficiency.

In this study, Greenlaw grew yeast in five different pH-adjusted media, followed by density-gradient separation of quiescent cells to determine the percentage of quiescent cells in each pH-adjusted medium.Using this method, quiescent cells are in the lower, denser (heavy) fraction. Most of these daughter cells are unbudded and maintain both viability and reproducibility. Furthermore, they are highly thermotolerant. In contrast, cells in the upper fraction - less dense (light)- are heterogeneous and have non-quiescent cells. They are also less resistant to heat stress than quiescent cells.

Greenlaw found that ~90% of cells were quiescent at a low pH (pH=4) compared to ~25% at a higher pH (pH=8.24). To verify that the denser fraction contains cells that are truly quiescent, the team took advantage of the fact that quiescent cells have a high thermal tolerance. Greenlaw found that cells in the denser fraction were able to survive heat shock at 51°C, regardless of pH, indicating that these cells represent true quiescent cells. “This suggests that the increased quiescence entry yields from the media with pH 4.0 and 5.56 are the result of additional bona fide quiescent cells,” Greenlaw said.

Acidic pH promotes quiescence entry. A. Bar graph showing the total yeast produced by each media condition. OD=optical density. B. Bar graph showing the percent quiescent (Q) cells produced by each media condition.
Acidic pH promotes quiescence entry. A. Bar graph showing the total yeast produced by each media condition. OD=optical density. B. Bar graph showing the percent quiescent (Q) cells produced by each media condition. Image taken from the article

Furthermore, Greenlaw investigated whether the initial pH of the medium might change over time, thereby affecting the process of cells entering quiescence. To test this, the team measured the initial pH and the final pH after seven days. There was a slight difference between the pH over the course of the experiment, which may contribute to the entry of cells into quiescence. The mechanisms underlying these pH changes, however, remain unknown. “Further work will be necessary to understand what metabolic processes produce these pH changes, and how they are affected by initial pH. Whether the final pH of the culture is incidental, or a driving factor of altered quiescence entry is unclear,” Greenlaw stated.

Overall, Greenlaw’s findings indicate that acidic pH promotes yeast quiescence entry.


The spotlighted research was funded by the National Institute of General Medical Sciences. 

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium member Dr. Toshio Tsukiyamacontributed to this work.

Greenlaw, A; Dell, R; Tsukiyama, T (2024). Initial acidic media promotes quiescence entry in Saccharomyces cerevisiae. microPublication Biology. 10.17912/micropub.biology.001071