MITOCHONDRIAL GRPE MODULATES THE FUNCTION OF MATRIX HSP70 IN TRANSLOCATION AND MATURATION OF PREPROTEINS

Mitochondrial GrpE (Mge1p) is a mitochondrial cochaperone essential fo r viability of the yeast Saccharomyces cerevisiae. To study the role o f Mge1p in the biogenesis of mitochondrial proteins, we isolated a con ditional mutant allele of MGE1 which conferred a temperature-sensitive growth phenotype and led to the accumulation of mitochondrial preprot eins after shifting of the cells to the restrictive temperature. The m utant Mge1 protein was impaired in its interaction with the matrix hea t shock protein mt-Hsp70. The mutant mitochondria shelved a delayed me mbrane translocation of preproteins, and the maturation of imported pr oteins was impaired, as evidenced by the retarded second proteolytic p rocessing of a preprotein in the matrix. Moreover, the aggregation of imported proteins was decreased in the mutant mitochondria. The mutant Mge1p differentially modulated the interaction of mt-Hsp70 with prepr oteins compared with the wild type, resulting in decreased binding to preproteins in membrane transit and enhanced binding to fully imported proteins. We conclude that the interaction of Mge1p with mt-Hsp70 pro motes the progress of the Hsp70 reaction cycle, which is essential for import and maturation of mitochondrial proteins.