Multiple pathways in the integration of proteins into the mitochondrial outer membrane

Proteins residing in the mitochondrial outer membrane facilitate various interactions between the organelle and the rest of the eukaryotic cell. All these proteins are encoded in the nucleus and synthesized on cytosolic ribosomes. Thus, they have to bear appropriate signals that ensure both their correct import into the organelle and their ability to acquire different topologies in the lipid bilayer. None of these proteins contain a canonical cleavable N-terminal presequence. Rather, the targeting and sorting signals can be found at their termini or in internal structural elements. In this review, we summarize the current knowledge regarding the diverse molecular mechanisms by which mitochondrial outer membrane proteins are specifically targeted to the organelle and inserted into the target membrane. Recognition events in the diverse pathways and the driving force for the various stages of this process will be discussed. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes.