Fig. 4. Model for regulation of osmosensitive gene expression by disruption of protein homeostasis. Hypertonic stress induced water loss causes elevated cytoplasmic ionic strength, which in turn disrupts new protein synthesis and cotranslational protein folding (see Lamitina et al., 2006). Damaged proteins function as a signal that activates gpdh-1 expression and glycerol synthesis. Glycerol replaces inorganic ions in the cytoplasm and functions as a chemical chaperone that aids in the refolding of misfolded proteins. Loss of function of protein homeostasis genes also causes accumulation of damaged proteins and activation of gpdh-1 expression.