THE ROLE OF THE GRPE HOMOLOG, MGE1P, IN MEDIATING PROTEIN IMPORT AND PROTEIN-FOLDING IN MITOCHONDRIA

Mge1p, a mitochondrial GrpE homologue, has recently been identified in the yeast Saccharomyces cerevisiae and a role for this protein in pre cursor import has been reported. To dissect the molecular mechanism of Mge1p function, conditional mge1 mutants were constructed. Cells harb ouring mutant mge1 accumulated precursor proteins at restrictive tempe rature. Both kinetics and efficiency of import were reduced in mitocho ndria isolated from strains possessing mutant mge1. Binding of mitocho ndrial-Hsp70 (mt-Hsp70) to incoming precursor proteins was abolished a t restrictive temperature. Nucleotide-dependent dissociation of mt-Hsp 70 from the import component MIM44 was reduced in mitochondria from mu tant mge1 strains, Furthermore, at restrictive temperature an increase of incompletely folded, newly imported protein and enhanced protein a ggregation was observed in mitochondria isolated from the mutant strai ns. We conclude that Mge1p exerts an essential function in import and folding of proteins by controlling the nucleotide-dependent binding of mt-Hsp70 to substrate proteins and the association of mt-Hsp70 with M IM44.