Specific recognition of mitochondrial preproteins by the cytosolic domain of the import receptor MOM72

Abstract The import receptor MOM72 constitutes part of the protein translocation machinery of the outer mitochondrial membrane, the receptor-general insertion pore complex. The protein contains a membrane anchor at the NH2 terminus and a large cytosolic domain. In yeast and Neurospora crassa the cytosolic domain comprises about 570-580 amino acid residues. The cytosolic domain of yeast MOM72 was purified after expression in Escherichia coli as a homogeneous monomeric protein. It can recognize precursor proteins as demonstrated by its ability to compete for binding and import into the mitochondria and to physically interact with preproteins. A subset of preproteins including the ADP/ATP carrier and the phosphate carrier interact with very high affinity, precursors that are known to be targeted via MOM72. Thus, the cytosolic domain of MOM72 plays a critical function in the recognition of preproteins by directly binding to precursor proteins and thereby facilitating their targeting to mitochondria.