Protein Translocation into Mitochondria and ER

For most proteins of the ER, translocation is coupled with protein synthesis. The synthesis of the growing polypeptide from the ribosome docked onto the ER is sufficient to drive the forward movement of the preprotein into the organelle (Fig. 1 Walter andjohnson, 1994 Matlack et al., 1998). However, it was found that some ER-targeted proteins, especially those found in yeast, could be imported into this organelle in a posttranslational fashion. Thus, in such cases the ribosome can play no part in driving preprotein translocation. Indeed an in vitro ER protein import assay has been developed that utilizes fully synthesized preproteins (Hansen et al., 1986 Rothblatt and Meyer, 1986 Waters and Blobel, 1986), and at least one ER-directed preprotein has been shown to be folded in the cytosol before its translocation into the organelle (Paunola et al., 1998). It seems that for yeast, posttranslational import utilizes the same ER Sec61 translocation channel as that employed in the cotranslational system however, additional factors are also recruited to the complex (Fig. 1 Panzer etal., 1995). 

The majority of mitochondria-destined preproteins seem to be imported after completion of polypeptide synthesis (Pfanner et al., 1997 Herrmann and Neupert, 2000). Preproteins are targeted to the outer membrane, often via N-terminal signals, where they bind to translo-case components of the outer membrane (TOM). Preproteins subsequently translocate across the general import pore (Ryan and Pfanner, 1998). Extra complexity is introduced into matrix-imported preproteins because they must also translocate across the inner membrane (Fig. 2). This is achieved via interactions of the preproteins with the translocase 

Early studies showed that ATP was needed for preprotein import into mitochondria however, there was some debate regarding whether this 

ATP was also shown to be required for the posttranslational import of preproteins into the ER lumen (Hansen et al., 1986 Rothblatt and Meyer, 1986 Waters and Blobel, 1986). The requirement was found to be subsequent to preprotein binding to the ER membrane (Sanz and Meyer, 1989). 

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