Three trehalases ATH1, NTH1, and NTH2 have been identified in Saccharomyces cerevisiae. ATH1, and NTH1 hydrolyze trehalose to glucose to provide energy and assist in recovery from stress. Human trehalase (TREH) is expressed in the intestine and kidney and probably hydrolyzes ingested trehalose in the intestine and acts as marker of renal tubular damage in kidney. Since trehalose is not present in Circulation or kidney tubules, its renal effect suggests it has other yet unidentified actions. Here we examined the function of human trehalase in budding yeast. We constructed three yeast trehalase Mutants (NTH1 Delta, NTH2 Delta, and ATH1 Delta) and then transformed TREH into these mutants. NTH1 Delta did not grow on media containing trehalose as the carbon source, and TREH did not rectify NTH1 Delta dysfunction and also did not grow oil trehalose medium, Suggesting that TREH is not responsible for utilization of exogenous trehalose in yeast. In experiments involving exposure to heat, osmotic and oxidative stresses, NTH1 Delta showed no recovery. Interestingly, ATH1 Delta-TREH showed high sensitivity to all three stressors. ATH1 Delta and NTH2 Delta showed very low neutral trehalase activity and NTH1 Delta did not show any neutral trelialase activity, and trehalose concentrations were higher. Increased neutral trehalase activity (equivalent to the wild type), reduction of trehalose content and brisk sensitivity to stressors were noted in TREH-ATH1 Delta strain, but not in TREH-NTH1 Delta or -NTH2 Delta. Our results Suggest that TREH acts as a stress-response protein in the kidney rather than involved in utilization of exogenous trehalose. 2008 (C) Elsevier Inc. All rights reserved.