Short Answer 55. How do proteins targeted to the mitochondrial matrix reach their destination? Solution Proteins imported into the matrix of mitochondria are usually taken up from the cytosol within seconds or minutes of their release from ribosomes. Thus, in contrast to the protein translocation into the ER described later, mitochondrial proteins are first fully synthesized as precursor proteins in the cytosol and then translocated into mitochondria by a posttranslational mechanism. Most of the mitochondrial precursor proteins have a signal sequence at their N terminusthat is rapidly removed after import by a protease (the signal peptidase) in the mitochondrial matrix. The signal sequences are both necessary and sufficient for import of the proteins that contain them: through the use of genetic engineering techniques, these signals can be linked to any cytosolic protein to direct the protein into the mitochondrial matrix. Sequence comparisons and physical studies of different matrix signal sequences suggest that their common feature is the propensity to fold into an amphipathic ? helix, in which positively charged residues are clustered on one side of the helix, while uncharged hydrophobic residues are clustered on the opposite side. This configuration—rather than a precise amino acid sequence—is recognized by specific receptor proteins that initiate protein translocation. .