A Putative Bet-Hedging Strategy Buffers Budding Yeast against Environmental Instability

Laura E Bagamery,Quincey A Justman,Ethan C Garner,Andrew W Murray

doi:10.1016/j.cub.2020.08.092

Abstract

To grow and divide, cells must extract resources from dynamic and unpredictable environments. Many organisms use different metabolic strategies for distinct contexts. Budding yeast can produce ATP from carbon sources by mechanisms that prioritize either speed (fermentation) or yield (respiration). Withdrawing glucose from exponentially growing cells reveals variability in their ability to switch from fermentation to respiration. We observe two subpopulations of glucose-starved cells: recoverers, which rapidly adapt and resume growth, and arresters, which enter a shock state characterized by deformation of many cellular structures, including mitochondria. These states are heritable, and on high glucose, arresters grow and divide faster than recoverers. Recoverers have a fitness advantage during a carbon source shift but are less fit in a constant, high-glucose environment, and we observe natural variation in the frequency of the two states across wild yeast strains. These experiments suggest that bet hedging has evolved in budding yeast.

Highlights

Metabolic flexibility—the ability to alternate between distinct metabolic pathways for performing functionally interchangeable anabolic and catabolic activities—allows cells to modulate their metabolism dynamically in response to external nutrient supplies, which often vary widely in quantity and quality
The budding yeast, Saccharomyces cerevisiae, can use multiple metabolic strategies to derive energy from carbon: in conditions permitting high consumption rates of their preferred carbon source, glucose, yeast rely on glycolysis and fermentation for the generation of ATP and biomass; cells perform respiration, a process with a higher ATP yield per unit sugar, when glucose is scarce and when they depend on a carbon source that can only be metabolized through oxidation [1, 2]
To assess whether mitochondrial network morphology reports on metabolic state, we examined mitochondria in cells growing in a variety of carbon sources

Summary

Introduction

Metabolic flexibility—the ability to alternate between distinct metabolic pathways for performing functionally interchangeable anabolic and catabolic activities—allows cells to modulate their metabolism dynamically in response to external nutrient supplies, which often vary widely in quantity and quality. Budding yeast prefer to ferment, a bias that is enforced by catabolite repression, a complex and overlapping set of regulatory networks that repress the expression of proteins involved in respiration even in the presence of oxygen and carbon sources that can be oxidized [4]. Mitochondria exist as a network of branched tubules along the cell cortex. Mitochondrial network size and structure are flexible and responsive to environmental conditions: cells in the presence of high glucose possess minimal mitochondrial networks that can become more branched and increase in volume when forced to utilize a nonfermentable carbon source, such as glycerol [5,6,7,8]

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Discussion

Conclusion