Mitochondrial biogenesis: The Tom and Tim machine

More than 98 % of the 1000 or so distinct mitochondrial proteins are encoded in the nucleus and synthesized as precursors in the cytosol. The preproteins are kept in a translocation-competent conformation by interactions with cytosolic chaperones, and are targeted to the preprotein translocase of the outer mitochondrial membrane (Tom) that includes receptors proteins and a general import pore. Transport across the inner mitochondrial membrane is mediated by the Tim machinery. Both the electrical potential gradient (Dc) across the inner membrane and the heat shock protein 70 (Hsp70) of the mitochondrial matrix are crucial for driving polypeptide translocation. A large number of components involved in mitochondrial protein import have been identified [1–5]. Recent studies show that neither the Tom machinery nor the Tim machinery are stable protein complexes. Their subunits are organized in subcomplexes that interact in a dynamic manner with each other and molecular chaperones. Here we discuss this dynamic organization, which represents a key principle underlying the various tasks of the protein import machinery, such as the generation of a driving force for translocation, and the unfolding and sorting of preproteins.