HSP78, A CLP HOMOLOG WITHIN MITOCHONDRIA, CAN SUBSTITUTE FOR CHAPERONE FUNCTIONS OF MT-HSP70

Hsp78 is a Clp homologue within mitochondria of Saccharomyces cerevisi ae. Deletion of HSP78 does not cause any detectable changes in wild ty pe cells, but results in a petite phenotype in the ssc1-3 mutant strai n carrying a temperature-sensitive allele of mt-hsp70. When overexpres sed in the ssc1-3 mutant strain, hsp78 suppresses the defect in mitoch ondrial protein import under permissive conditions in vitro and intera cts directly with newly imported polypeptide chains. As a molecular ch aperone, hsp78 prevents the aggregation of misfolded proteins in the m atrix of mitochondria under conditions of impaired mt-hsp70 function. However, unlike misfolded proteins associated with mt-hsp70, hsp78-bou nd polypeptides are not efficiently degraded by the ATP-dependent PIM1 protease. Thus, hsp78 can partially substitute for mt-hsp70 functions in the assembly of mitochondria and may be part of a salvage pathway if mt-hsp70 is limiting.