Trehalose Is a Versatile and Long-Lived Chaperone for Desiccation Tolerance

• Published in: Current biology Vol. 24; no. 23; pp. 2758 - 2766
• Main Authors: Tapia, Hugo, Koshland, Douglas E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2014
• Subjects: Dehydration; Heat-Shock Proteins - metabolism; Molecular Chaperones - metabolism; Protein Folding; Saccharomyces cerevisiae; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - physiology; Saccharomyces cerevisiae Proteins - metabolism; Trehalose - metabolism
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2014.10.005

Diverse organisms across taxa are desiccation tolerant, capable of surviving extreme water loss. Remarkably, desiccation tolerant organisms can survive years without water. However, the molecular mechanisms underlying this rare trait are poorly understood.
Here, using Saccharomyces cerevisiae, we show that intracellular trehalose is essential for survival to long-term desiccation. The time frame for maintaining long-term desiccation tolerance consists of a balance of trehalose stockpiled prior to desiccation and trehalose degradation by trehalases in desiccated cells. The activity of trehalases in desiccated cell reveals the stunning ability of cells to retain enzymatic activity while desiccated. Interestingly, the protein chaperone Hsp104 compensates for loss of trehalose during short-term, but not long-term, desiccation. We show that desiccation induces protein misfolding/aggregation of cytoplasmic and membrane proteins using luciferase and prion reporters. We demonstrate that trehalose, but not Hsp104, mitigates the aggregation of both cytoplasmic and membrane prions. We propose that desiccated cells initially accumulate both protein and chemical chaperones, like Hsp104 and trehalose, respectively. As desiccation extends, the activities of the protein chaperones are lost because of their complexity and requirement for energy, leaving trehalose as the major protector against the aggregation of cytoplasmic and membrane proteins.
Our results suggest that trehalose is both a more stable and more versatile protectant than protein chaperones, explaining its important role in desiccation tolerance and emphasizing the translational potential of small chemical chaperones as stress effectors.
•Trehalose is essential for survival to long-term desiccation•Trehalose is a more versatile chaperone than protein chaperones, e.g., Hsp104•Desiccated cells are enzymatically active, despite low water concentrations•Desiccation induces protein misfolding/aggregation that is mitigated by trehalose
Tapia and Koshland show that trehalose is essential for long-term desiccation tolerance in yeast. Trehalose mitigates desiccation-induced proteotoxicity of aggregation-prone membrane and cytoplasmic proteins. These studies provide insights into the in vivo potential of small chemical chaperones to act as stable and versatile stress effectors.