DYNAMICS OF THE TOM COMPLEX OF MITOCHONDRIA DURING BINDING AND TRANSLOCATION OF PREPROTEINS

Translocation of preproteins across the mitochondrial outer membrane i s mediated by the TOM complex. This complex consists of receptor compo nents for the initial contact with preproteins at the mitochondrial su rface and membrane-embedded proteins which promote transport and form the translocation pare. Tn order to understand the interplay between t he translocating preprotein and the constituents of the TOM complex, w e analyzed the dynamics of the TOM complex of Neurospora crassa and Sa ccharomyces cerevisiae mitochondria by following the structural altera tions of the essential pore component Tom40 during the translocation o f preproteins. Tom40 exists in a homo-oligomeric assembly and dynamica lly interacts with Tom6. The Tom40 assembly is influenced by a block o f negatively charged amino acid residues in the cytosolic domain of To m22, indicating a cross-talk between preprotein receptors and the tran slocation pore. Preprotein binding to specific sites on either side of the outer membrane (cis and trans sites) induces distinct structural alterations of Tom40. To a large extent, these changes are mediated by interaction with the mitochondrial targeting sequence. We propose tha t such targeting sequence-induced adaptations are a critical feature o f translocases in order to facilitate the movement of preproteins acro ss cellular membranes.