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A large number of newly-synthesized polypeptides must cross one or
several intracellular membranes to reach their functional locations
in the eukaryotic cell. The mechanisms of protein trafficking, in
particular the post-translational targeting and membrane
translocation of proteins, are of fundamental biological importance
and are the focus of intensive research world-wide. For more than
15 years, mitochondria have served as the paradigm organelle system
to study these processes. Although key questions, such as how
precisely proteins cross a membrane, still remain to be answered,
exciting progress has been made in understanding the basic pathways
of protein import into mitochondria and the components involved. In
addition to a fascinating richness and complexity in detail, the
analysis of mitochondrial protein import has revealed mechanistic
principles of general significance: Major discoveries include the
demonstration of the requirement of an unfolded state for
translocation and of the essential role of molecular chaperones on
both sides of the membranes in maintaining a
translocation-competent conformation and in protein folding after
import. It is becoming clear how a polypeptide chain is "reeled"
across the membrane in an ATP-dependent process by the functional
cooperation of membrane proteins, presumably constituting part of a
transmembrane channel, with peripheral components at the trans-side
of the membrane.
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