Mitochondrial proteins at unexpected cellular locations: export of proteins from mitochondria from an evolutionary perspective.
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Researchers in a wide variety of unrelated areas studying functions of different proteins are unexpectedly finding that their proteins of interest are actually mitochondrial proteins, although functions would appear to be extramitochondrial. We review the leading current examples of mitochondrial macromolecules indicated to be also present outside of mitochondria that apparently exit from mitochondria to arrive at their destinations. Mitochondrial chaperones, which have been implicated in growth and development, autoimmune diseases, cell mortality, antigen presentation, apoptosis, and resistance to antimitotic drugs, provide some of the best studied examples pointing to roles for mitochondria and mitochondrial proteins in diverse cellular phenomena. To explain the observations, we propose that specific export mechanisms exist by which certain proteins exit mitochondria, allowing these proteins to have additional functions at specific extramitochondrial sites. Several possible mechanisms by which mitochondrial proteins could be exported are discussed. Gram-negative proteobacteria, from which mitochondria evolved, contain a number of different mechanisms for protein export. It is likely that mitochondria either retained or evolved export mechanisms for certain specific proteins.
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