MITOCHONDRIAL PRESEQUENCES CAN INDUCE AGGREGATION OF UNFOLDED PROTEINS

We have studied the interactions between various synthetic peptides an d two model unfolded proteins, reduced alpha-lactalbumin and reduced a nd carboxymethylated alpha-lactalbumin. We found that mitochondrial pr esequences could induce aggregation of the unfolded alpha-lactalbumins but not of the native alpha-lactalbumin. The presequence-induced aggr egation of unfolded alpha-lactalbumin was dependent on electrostatic i nteractions and on the amphiphilicity of the presequences. Since posit ive charge and amphiphilicity are necessary for the targeting function of mitochondrial presequences, presequence-induced aggregation may be responsible for the instability of mitochondrial precursor proteins a nd may need to be inhibited by binding factors in the cytosol.