Hsp104 is required for tolerance to many forms of stress.

Abstract

Heat-shock proteins (hsps) are induced by many types of stress. In Saccharomyces cerevisiae, a mutation in the HSP104 gene, a member of the highly conserved hsplOO gene family, reduces the ability of log-phase fermenting cells to withstand high temperatures after mild, conditioning pretreatments. Here, we examine the expression of hsplO4 and its importance for survival under many different conditions. HsplO4 is expressed at a higher level in respiring cells than in fermenting cells and is required for the unusually high basal thermotolerance of respiring cells. Its expression in stationary phase cells and spores is crucial for the naturally high thermotolerance of these cell types and for their long-term viability at low temperatures. The protein is of critical importance in tolerance to ethanol and of moderate importance in tolerance to sodium arsenite. Thus, the hsplO4 mutation establishes the validity of a long-standing hypothesis in the heat-shock field, namely, that hsps have broadly protective functions. Further, that a single protein is responsible for tolerance to heat, ethanol, arsenite and long-term storage in the cold indicates that the underlying causes of lethality are similar in an extraordinary variety of circumstances. Finally, the protein is of little or no importance in tolerance to copper and cadmium, suggesting that the lethal lesions produced by these agents are fundamentally different from those produced by heat.

Genetic evidence for a functional relationship between Hsp104 and Hsp70

“…Although the deletion of HSP104 decreased thermotolerance, no additional effect was observed with the deletion of HSP26 (Fig. 3) (26).…”

“…The high level of basal thermotolerance of cells in acetate and galactose is, in large part, due to the higher level of constitutive expression of heat shock proteins, particularly HsplO4. Stationary-phase cells and spores also exhibit a high level of basal thermotolerance, again in part due to the high level of constitutive expression of HsplO4 in these cell types (26). In cells with a low level of basal tolerance, brief conditioning treatments at moderately high temperatures (e.g., 30 min at 37°C) produce a dramatic increase (induced thermotolerance).…”

Dominant Gain-of-Function Mutations in Hsp104p Reveal Crucial Roles for the Middle Region

“…For example, yeast cells expressing Hsp104p are 1000 times more viable after exposure to temperatures Ն50°C or to an ethanol concentration of 20% than cells carrying deletions of HSP104 (Sanchez and Lindquist, 1990;Sanchez et al, 1992). This survival capacity is directly attributable to Hsp104p's ability to resolubilize protein aggregates and, together with Hsp70p and Hsp40p, return them to their folded and active states (Parsell et al, 1994;Glover and Lindquist, 1998;Goloubinoff et al, 1999).…”

The co-chaperone SGT of Leishmania donovani is essential for the parasite's viability

“…For instance, the HSP100 (ClpB) does not mediate temperature tolerance, nor does it form homohexameric complexes (Krobitsch et al 1998;Krobitsch and Clos 1999) as does its counterpart in yeast (Sanchez and Lindquist 1990;Sanchez et al 1992;Parsell and Lindquist 1994). We are only beginning to understand the functional variability of the chaperones and co-chaperones between different phyla and how this affects the operative range of client proteins that are activated by molecular chaperones (Johnson and Brown 2009).…”