THE MOLECULAR CHAPERONE HSP78 CONFERS COMPARTMENT-SPECIFIC THERMOTOLERANCE TO MITOCHONDRIA

Hsp78, a member of the family of Clp/Hsp100 proteins, exerts chaperone functions in mitochondria of S. cerevisiae which overlap with those o f mitochondrial Hsp70. In the present study, the role of Hsp78 under e xtreme stress was analyzed. Whereas deletion of HSP78 does not affect cell growth at temperatures up to 39 degrees C and cellular thermotole rance at 50 degrees C, Hsp78 is crucial for maintenance of respiratory competence and for mitochondrial genome integrity under severe temper ature stress (mitochondrial thermotolerance). Mitochondrial protein sy nthesis is identified as a thermosensitive process. Reactivation of mi tochondrial protein synthesis after heat stress depends on the presenc e of Hsp78, though Hsp78 does not confer protection against heat-inact ivation to this process. Hsp78 appears to act in concert with other mi tochondrial chaperone proteins since a conditioning pretreatment of th e cells to induce the cellular heat shock response is required to main tain mitochondrial functions under severe temperature stress, When exp ressed in the cytosol, Hsp78 can substitute for the homologous heat sh ock protein Hsp104 in mediating cellular thermotolerance, suggesting a conserved mode of action of the two proteins. Thus, proteins of the C lp/Hsp100-family located in the cytosol and within mitochondria confer compartment-specific protection against heat damage to the cell.