Characterizing the in vivo role of trehalose in<i>Saccharomyces cerevisiae</i>using the<i>AGT1</i>transporter

Gibney, Patrick A.; Schieler, Ariel; Chen, Jonathan C.; Rabinowitz, Joshua D.; Botstein, David

doi:10.1073/pnas.1506289112

Cited by 81 publications

(80 citation statements)

References 51 publications

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“…A more recent report, however, suggests that trehalose per se has no, or negative, effects on yeast cells and that the effects observed in mutants with defective trehalose synthesis rather are due to a role of trehalose metabolism in central metabolic control 38 . Intracellular trehalose levels have been negatively correlated with specific growth rate of the cells, i.e.…”

Section: Discussionmentioning

confidence: 97%

The yeast osmostress response is carbon source dependent

Babazadeh

Lahtvee

Adiels

et al. 2017

Sci Rep

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Adaptation to altered osmotic conditions is a fundamental property of living cells and has been studied in detail in the yeast Saccharomyces cerevisiae. Yeast cells accumulate glycerol as compatible solute, controlled at different levels by the High Osmolarity Glycerol (HOG) response pathway. Up to now, essentially all osmostress studies in yeast have been performed with glucose as carbon and energy source, which is metabolised by glycolysis with glycerol as a by-product. Here we investigated the response of yeast to osmotic stress when yeast is respiring ethanol as carbon and energy source. Remarkably, yeast cells do not accumulate glycerol under these conditions and it appears that trehalose may partly take over the role as compatible solute. The HOG pathway is activated in very much the same way as during growth on glucose and is also required for osmotic adaptation. Slower volume recovery was observed in ethanol-grown cells as compared to glucose-grown cells. Dependence on key regulators as well as the global gene expression profile were similar in many ways to those previously observed in glucose-grown cells. However, there are indications that cells re-arrange redox-metabolism when respiration is hampered under osmostress, a feature that could not be observed in glucose-grown cells.

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Section: Discussionmentioning

confidence: 97%

The yeast osmostress response is carbon source dependent

Babazadeh

Lahtvee

Adiels

et al. 2017

Sci Rep

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“…The majority of studies that have previously implicated trehalose as a stress protectant rely on purely correlative data and are based on in vitro studies. Indeed, in a companion paper, Gibney et al demonstrate that introduction of trehalose into naïve yeast cells does not confer tolerance to heat shock, nor does it aid in a variety of other roles to which trehalose has been previously assigned (20).…”

Section: Discussionmentioning

confidence: 99%

“…A third potential indirect mechanism for trehalose-induced desiccation tolerance came from the observation that wild-type cells grown in minimal medium expressing TDH3pr-AGT1 exhibit slower growth rates after addition of trehalose to the media and induced the environmental stress response (ESR) after ∼2 h (20). The ESR induces increased synthesis of additional stress effectors besides trehalose (21).…”

Section: Import Of Extracellular Trehalose Confers Robust Desiccationmentioning

confidence: 99%

Increasing intracellular trehalose is sufficient to confer desiccation tolerance to Saccharomyces cerevisiae

Tapia

Young

Fox³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

146

132

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Diverse organisms capable of surviving desiccation, termed anhydrobiotes, include species from bacteria, yeast, plants, and invertebrates. However, most organisms are sensitive to desiccation, likely due to an assortment of different stresses such as protein misfolding and aggregation, hyperosmotic stress, membrane fracturing, and changes in cell volume and shape leading to an overcrowded cytoplasm and metabolic arrest. The exact stress(es) that cause lethality in desiccation-sensitive organisms and how the lethal stresses are mitigated in desiccation-tolerant organisms remain poorly understood. The presence of trehalose in anhydrobiotes has been strongly correlated with desiccation tolerance. In the yeast Saccharomyces cerevisiae, trehalose is essential for survival after long-term desiccation. Here, we establish that the elevation of intracellular trehalose in dividing yeast by its import from the media converts yeast from extreme desiccation sensitivity to a high level of desiccation tolerance. This trehalose-induced tolerance is independent of utilization of trehalose as an energy source, de novo synthesis of other stress effectors, or the metabolic effects of trehalose biosynthetic intermediates, indicating that a chemical property of trehalose is directly responsible for desiccation tolerance. Finally, we demonstrate that elevated intracellular maltose can also make dividing yeast tolerant to short-term desiccation, indicating that other disaccharides have stress effector activity. However, trehalose is much more effective than maltose at conferring tolerance to long-term desiccation. The effectiveness and sufficiency of trehalose as an antagonizer of desiccation-induced damage in yeast emphasizes its potential to confer desiccation tolerance to otherwise sensitive organisms.trehalose | desiccation | yeast | anhydrobiosis | stress

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“…For example, a recent work with the surface-additive method [33,34] elucidated the unique feature of Tre that underlies its diverse effects on proteins, namely favorable interactions with amide groups and anionic oxygen and unfavorable interactions with aliphatic carbons [35]. The finding stands in marked contrast to a report on the yeast Saccharomyces cerevisiae, in which the authors proved that accumulation of intracellular Tre per se does not improve thermotolerance and proposed that the physiological role of Tre is fundamentally metabolic [36]. Using the mycobacterial Tre-specific transporter, we demonstrated that build-up of intracellular Tre accounts for the OtsA R328H -dependent thermotolerance.…”

Section: Discussionmentioning

confidence: 86%

Trehalose acts as a uridine 5′‐diphosphoglucose‐competitive inhibitor of trehalose 6‐phosphate synthase in Corynebacterium glutamicum

Oide

Inui

2017

The FEBS Journal

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Trehalose is a compatible solute widely distributed in nature. The most prevalent pathway for its synthesis starts from condensation of glucose 6-phosphate (Glc6P) and uridine 5'-diphosphoglucose (UDP-Glc) catalyzed by trehalose 6-phosphate synthase (TPS). A previous laboratory evolution experiment with the bacterium Corynebacterium glutamicum generated strains adapted to supraoptimal temperatures, and the R328H substitution of the TPS encoded by otsA was shown to be associated with thermotolerance acquired by the evolved strains. In this study, we found that the OtsA:R328H substitution promotes both intra- and extracellular trehalose accumulation and demonstrated that build-up of intracellular trehalose accounts for the OtsA -dependent thermotolerance, using the mycobacterial trehalose-specific transporter. Counterintuitively, characterization of the recombinant OtsA proteins revealed that the mutation downshifts the temperature optimum of OtsA. A search for the molecular basis of OtsA -dependent enhancement of trehalose synthesis led to the unexpected findings that trehalose is an effective inhibitor of OtsA and that OtsA is highly tolerant to the trehalose-mediated inhibition. The only available report on such feedback regulation of TPS is for the silk moth from over 50 years ago [Murphy TA and Wyatt GR (1965) J Biol Chem 240, 1500-1508]. While trehalose acts as a Glc6P-competitive inhibitor in the silk moth, the disaccharide was found to inhibit OtsA in a UDP-Glc-competitive manner in C. glutamicum, suggesting independent origins of the negative feedback regulations found for the two species. We showed that overexpression of the wild-type OtsA counteracts the trehalose-dependent regulation and restores the evolved strain-like phenotype to the isogenic wild-type otsA revertant, demonstrating that thermotolerance conferred by OtsA is attributable to its feedback-resistant property.

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Characterizing the in vivo role of trehalose inSaccharomyces cerevisiaeusing theAGT1transporter

Cited by 81 publications

References 51 publications

The yeast osmostress response is carbon source dependent

The yeast osmostress response is carbon source dependent

Increasing intracellular trehalose is sufficient to confer desiccation tolerance to Saccharomyces cerevisiae

Trehalose acts as a uridine 5′‐diphosphoglucose‐competitive inhibitor of trehalose 6‐phosphate synthase in Corynebacterium glutamicum

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