Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals

The disaccharide trehalose, which accumulates dramatically during heat shoc k and stationary phase in many organisms, enhances thermotolerance and redu ces aggregation of denatured proteins. Here we re port a new role for treha lose in protecting cells against oxygen radicals. Exposure of Saccharomyces cerevisiae to a mild heat shock (38 degreesC) or to a proteasome inhibitor (MG132) induced trehalose accumulation and markedly increased the viabilit y of the cells upon exposure to a free radical-generating system (H2O2/iron ). When cells were returned to normal growth temperature (28 degreesC) or M G132 was removed from the medium, the trehalose content and resistance to o xygen radicals decreased rapidly, Furthermore, a mutant unable to synthesiz e trehalose was much more sensitive to killing by oxygen radicals than wild -type cells. Providing trehalose exogenously enhanced the resistance of mut ant cells to H2O2. Exposure of cells to H2O2 caused oxidative damage to ami no acids in cellular proteins, and trehalose accumulation was found to redu ce such damage. After even brief exposure to H2O2, the trehalose-deficient mutant exhibited a much higher content of oxidatively damaged proteins than wild-type cells. Trehalose accumulation decreased the initial appearance o f damaged proteins, presumably by acting as a free radical scavenger. There fore, trehalose accumulation in stressed cells plays a major role in protec ting cellular constituents from oxidative damage.