RECOGNITION AND BINDING OF MITOCHONDRIAL PRESEQUENCES DURING THE IMPORT OF PROTEINS INTO MITOCHONDRIA

Nuclear-encoded mitochondrial proteins are imported into mitochondria due to the presence of a targeting sequence, the presequence, on their amino termini. Presequences, which are typically proteolyzed after a protein has been imported into a mitochondrion, lack any strictly cons erved primary structure but are positively charged and are predicted t o form amphiphilic alpha-helices. Studies with synthetic peptides corr esponding to various presequences argue that presequences can partitio n nonspecifically into the mitochondrial outer membrane and that the s pecificity of translocation of precursors into mitochondria may depend on interactions of the presequence with the electrical potential of t he inner membrane. Although proteins of the outer membrane that are ne cessary for the translocation of precursor proteins have been proposed to function as receptors for presequences, the binding of presequence s to these proteins has not been demonstrated directly. Proteins of th e mitochondrial outer membrane may not be responsible for the specific ity of translocation of precursors but may instead function, together with cytosolic molecular chaperones, to maintain precursor proteins in conformations that are competent for translocation as the precursors associate with the mitochondrial surface.