Thermotolerance in Saccharomyces cerevisiae: the Yin and Yang of trehalose

doi:10.1016/S0167-7799(98)01251-7

Trends in Biotechnology

Volume 16, Issue 11, 1 November 1998, Pages 460-468

https://doi.org/10.1016/S0167-7799(98)01251-7 Get rights and content

Abstract

Trehalose, a sugar produced by a wide variety of organisms, has long been known for its role in protecting certain organisms from desiccation. Recent work in yeast indicates that trehalose also promotes survival under conditions of extreme heat, by enabling proteins to retain their native conformation at elevated temperatures and suppressing the aggregation of denatured proteins. The latter property, however, seems to impair the recovery of cells from heat shock if they fail to degrade trehalose after the stress has passed. These multiple effects of trehalose on protein stability and folding suggest a host of promising applications.

Section snippets

The synthesis of trehalose

Trehalose (α-d-glucopyranosyl-α-d-glucopyranoside) is a nonreducing disaccharide composed of two molecules of glucose linked at their 1-carbons. Although barely detectable in log-phase yeast growing on glucose, trehalose accumulates to remarkably high levels—up to 20% of the dry weight of the cell—in stationary-phase cells and spores, as well as in exponential-phase cells exposed to high temperatures[9]; cells growing on nonfermentable carbon sources have high levels of trehalose in both log

TPS1 and growth on glucose

An unexpected, and as-yet unexplained, phenotype of tps1 mutants is their inability to grow on readily-fermentable carbon sources, such as glucose. When placed in glucose-containing media, the cells become flooded with the sugar, which is readily phosphorylated by hexokinases to yield vast quantities of glucose-6-phosphate. Levels of ATP and free inorganic phosphate consequently plunge, presumably bringing critical cellular functions to a standstill[27]. Three explanations have been proposed to

Trehalose catabolism

Trehalose can be degraded by various trehalases (Table 1), which hydrolyse the disaccharide to yield two molecules of glucose[11]. Although trehalose has been detected exclusively in the nuclear-cytosolic compartment, trehalase activity is present both in this region and in the vacuole[30]. The vacuolar enzyme is constitutively active, with its pH optimum at 4.5 (`acid trehalase'). The activity of the cytosolic protein is maximal at pH 7 (`neutral trehalase') and is regulated by phosphorylation

Trehalose as an energy reserve?

For more than half a century after yeasts were found to produce trehalose, the disaccharide was primarily thought to serve as a storage carbohydrate39, 40, 41. This view was based on the observation that trehalose accumulates in physiological states in which energy storage is beneficial, such as stationary phase and sporulation. Correspondingly, trehalose is not produced when nutrients are abundant, as in exponential growth. The question remained, however, of why yeast requires a second energy

Trehalose as a stress protectant

A key contribution to understanding the function of trehalose in S. cerevisiae was the finding that the disaccharide is localized exclusively to the nuclear-cytosolic compartment[30]. Restriction of trehalose to this region (and its exclusion from other large spaces, such as the vacuole) results in cytosolic trehalose concentrations estimated at approximately 0.5 m[42], far greater than had previously been appreciated. Such high levels of the sugar, it was suggested, would dramatically affect

A combinatorial model for thermotolerance

The hypothesis that either Tps1p or trehalose is necessary for the production of Hsps derived from the above-mentioned observation that much lower levels of Hsps accumulate in heat-shock in tps1 mutants[51]. Under those conditions, however, cell viability was decreased[54]. With a heat treatment that did not reduce viability, metabolic labelling and western-blot analysis demonstrated no difference in the production or accumulation of Hsps in wild-type and tps1 cells. Yet under such conditions,

Potential applications

The protein-stabilization capacities of trehalose, elucidated by many laboratories, suggest a number of potential uses. These include enhancing the stress tolerance of commercially important organisms, facilitating the production of recombinant proteins and, in the long term, treating disorders resulting from protein instability and aggregation.

The ability to manipulate stress tolerance is desirable for a variety of agricultural and industrial uses. Efforts have already been made to increase

Acknowledgements

We are grateful to S. Hohmann for comments on the manuscript and for communicating results prior to publication. It is also a pleasure to thank H. Auer, E. Bertolino, A. Linden, S. Meredith and C. Quietsch for their help in translating historical references on trehalose.

References (71)

A.D Elbein
Adv. Carbohydr. Chem. Biochem.
(1974)
B Roser
Trends Food Sci. Technol.
(1991)
D Ang et al.
J. Biol. Chem.
(1991)
E Cabib et al.
J. Biol. Chem.
(1958)
K Winkler et al.
FEBS Lett.
(1991)
J.M Thevelein et al.
Trends Biochem. Sci.
(1995)
J.B van der Plaat et al.
Biochem. Biophys. Res. Commun.
(1974)
S Nwaka et al.
FEBS Lett.
(1995)
S Nwaka et al.
FEBS Lett.
(1996)
M Kopp et al.
J. Biol. Chem.
(1993)

S Nwaka et al.

J. Biol. Chem.

(1995)

S Nwaka

FEBS Lett.

(1994)

P.V Attfield

FEBS Lett.

(1987)

G.M Gadd et al.

FEMS Microbiol. Lett.

(1987)

T Hottiger et al.

FEBS Lett.

(1989)

B.W Hazell et al.

FEBS Lett.

(1995)

C Gross et al.

Biochem. Biophys. Res. Commun.

(1996)

T Hottiger et al.

FEBS Lett.

(1987)

M.A Singer et al.

Mol. Cell

(1998)

P.A Cole

Structure

(1996)

R Wetzel

Cell

(1996)

S.W Davies

Cell

(1997)

E Scherzinger

Cell

(1997)

J.H Crowe et al.

Annu. Rev. Physiol.

(1992)

P.W Piper

FEMS Microbiol. Rev.

(1993)

Parsell, D. A. and Lindquist, S. (1994) in The Biology of Heat Shock Proteins and Molecular Chaperones (Morimoto, R....

D.A Parsell et al.

Nature

(1994)

D.A Parsell et al.

Philos. Trans. R. Soc. London Ser. B

(1993)

Wiemken, A. (1990) Antonie van Leeuwenhoek Int. J. Gen. Mol. Microbiol. 58,...

P Van Dijck et al.

Appl. Environ. Microbiol.

(1995)

Nwaka, S. and Holzer, H. (1997) in Progress in Nucleic Acid Research and Molecular Biology (Moldave, K., ed.), pp....

L.F Leloir et al.

J. Am. Chem. Soc.

(1953)

O.E Vuorio et al.

Eur. J. Biochem.

(1993)

A Vandercammen et al.

Eur. J. Biochem.

(1989)

J Londesborough et al.

J. Gen. Microbiol.

(1991)

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Trends in Biotechnology

ReviewsThermotolerance in Saccharomyces cerevisiae: the Yin and Yang of trehalose

Abstract

Section snippets

The synthesis of trehalose

TPS1 and growth on glucose

Trehalose catabolism

Trehalose as an energy reserve?

Trehalose as a stress protectant

A combinatorial model for thermotolerance

Potential applications

Acknowledgements

Adv. Carbohydr. Chem. Biochem.

Trends Food Sci. Technol.

J. Biol. Chem.

J. Biol. Chem.

FEBS Lett.

Trends Biochem. Sci.

Biochem. Biophys. Res. Commun.

FEBS Lett.

FEBS Lett.

J. Biol. Chem.

J. Biol. Chem.

FEBS Lett.

FEBS Lett.

FEMS Microbiol. Lett.

FEBS Lett.

FEBS Lett.

Biochem. Biophys. Res. Commun.

FEBS Lett.

Mol. Cell

Structure

Cell

Cell

Cell

Annu. Rev. Physiol.

FEMS Microbiol. Rev.

Nature

Philos. Trans. R. Soc. London Ser. B

Appl. Environ. Microbiol.

J. Am. Chem. Soc.

Eur. J. Biochem.

Eur. J. Biochem.

J. Gen. Microbiol.

Reviews
Thermotolerance in Saccharomyces cerevisiae: the Yin and Yang of trehalose