Mechanisms of protein translocation into mitochondria

Mitochondrial biogenesis utilizes a complex proteinaceous machinery for the import of cytosolically synthesized preproteins. At least three large mult isubunit protein complexes, one in the outer membrane and two in the inner membrane, have been identified. These translocase complexes cooperate with soluble proteins from the cytosol, the intermembrane space and the matrix. The translocation of presequence-containing preproteins through the outer m embrane channel includes successive electrostatic interactions of the charg ed mitochondrial targeting sequence with a chain of import components. Tran slocation across the inner mitochondrial membrane utilizes the energy of th e proton motive force of the inner membrane and the hydrolysis of ATP. The matrix chaperone system of the mitochondrial heat shock protein 70 forms an ATP-dependent import motor by interaction with the polypeptide chain in tr ansit and components of the inner membrane translocase. The precursors of i ntegral inner membrane proteins of the metabolite carrier family interact w ith newly identified import components of the intermembrane space and are i nserted into the inner membrane by a second translocase complex. A comparis on of the full set of import components between the yeast Sacccharomyces ce revisiae and the nematode Caenorhabditis elegans demonstrates an evolutiona ry conservation of most components of the mitochondrial import machinery wi th a possible greater divergence for the import pathway of the inner membra ne carrier proteins. (C) 1999 Elsevier Science B.V. All rights reserved.