Practice question

Majority of mitochondrial proteins are encoded by nuclear genome synthesized in cytosol as precursors requiring active import. Matrix targeting signal resides typically at extreme N-terminus forming 15 to 70 amino acid extension lacking acidic residues and capable of adopting amphipathic alpha-helical conformation with positively charged lysine and arginine residues clustered on one face creating basic patch and hydrophobic leucine, phenylalanine on opposite face. This structure is recognized by receptor domains of translocase of outer membrane Tom20 with hydrophobic groove plus Tom22 acidic domain interacting with basic face. Precursor traverses Tom40 beta-barrel channel then outer to inner space, guided by Tim50 and translocase of inner membrane TIM23 complex where membrane potential Delta psi across inner membrane exerts electrophoretic attraction on positively charged residues and matrix Hsp70 ATP hydrolysis pulls polypeptide inward. Upon import, mitochondrial processing peptidase MPP cleaves presequence and chaperonin Hsp60 facilitates folding. Mutations disrupting amphipathicity cause mitochondrial import failure and disease phenotypes like Mohr-Tranebjaerg syndrome.