Dual targeting of mitochondrial proteins: Mechanism, regulation and function

One solution found in evolution to increase the number of cellular functions, without increasing the number of genes, is distribution of single gene products to more than one cellular compartment. It is well documented that in eukaryotic cells, molecules of one protein can be located in several subcellular locations, a phenomenon termed dual targeting, dual localization, or dual distribution. The differently localized proteins are coined in this review "echoforms" indicating repetitious forms of the same protein (echo in Greek denotes repetition) distinctly placed in the cell. This term replaces the term to "isoproteins" or "isoenzymes" which are reserved for proteins with the same activity but different amino acid sequences. Echoforms are identical or nearly identical, even though, as referred to in this review may, in some cases, surprisingly have a totally different function in the different compartments. With regard to mitochondria, our operational definition of dual targeted proteins refers to situations in which one of the echoforms is translocated through/into a mitochondrial membrane. In this review we ask how, when and why mitochondrial proteins are dual localized in the cell. We describe mechanisms of dual targeting of proteins between mitochondria and other compartments of the eukaryotic cell. In particular, we have paid attention to situations in which dual localization is regulated in time, location or function. In addition, we have attempted to provide a broader view concerning the phenomenon of dual localization of proteins by looking at mechanisms that are beyond our simple definition of dual targeting. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes.