Figure 2 | A hypothetical model for membrane insertion by the twin-pore translocase.   Multispanning, inner-membrane proteins that have internal targeting signals are inserted into the inner membrane by the translocase of the inner mitochondrial membrane (TIM)22 complex. The steps of transport can be experimentally dissected in vitro by modulating the membrane potential (). a | In the absence of a membrane potential, the TIM22 complex is inactivated (red traffic light). However, initial binding of the precursor to the translocase from the intermembrane-space side through the small Tim proteins Tim9–Tim10 and Tim12 can occur. This is the tethering step, and it resembles a subset of the stage-III-arrested carrier precursors (Box 4). b | At a low membrane potential (less than 60 mV), the pores of the translocation machinery are maintained in a partially-activated state (orange traffic light), and the low membrane potential is sufficient to promote the insertion of one precursor loop into the translocase (the membrane potential exerts an electrophoretic force on positive charges that are found in the matrix-exposed loops of the precursor). This is the docking step, and it resembles stage IV of carrier import. c | A high membrane potential (; for example, 120 mV) across the membrane, together with the recognition of an internal targeting signal in the precursor, fully activates the translocase (green traffic light). One pore closes tightly around the initially inserted terminal hairpin loop of the precursor, while the second pore mediates the insertion of the next set of transmembrane domains. The process leads to membrane insertion, which occurs by the lateral opening of the translocase (insertion step).

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© 2004 Nature Publishing Group