The selectivity filter of the mitochondrial protein import machinery
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RESEARCH ARTICLE
Open Access
The selectivity filter of the mitochondrial protein import machinery Sebastian Kreimendahl†, Jan Schwichtenberg†, Kathrin Günnewig, Lukas Brandherm and Joachim Rassow*
Abstract Background: The uptake of newly synthesized nuclear-encoded mitochondrial proteins from the cytosol is mediated by a complex of mitochondrial outer membrane proteins comprising a central pore-forming component and associated receptor proteins. Distinct fractions of proteins initially bind to the receptor proteins and are subsequently transferred to the pore-forming component for import. The aim of this study was the identification of the decisive elements of this machinery that determine the specific selection of the proteins that should be imported. Results: We identified the essential internal targeting signal of the members of the mitochondrial metabolite carrier proteins, the largest protein family of the mitochondria, and we investigated the specific recognition of this signal by the protein import machinery at the mitochondrial outer surface. We found that the outer membrane import receptors facilitated the uptake of these proteins, and we identified the corresponding binding site, marked by cysteine C141 in the receptor protein Tom70. However, in tests both in vivo and in vitro, the import receptors were neither necessary nor sufficient for specific recognition of the targeting signals. Although these signals are unrelated to the amino-terminal presequences that mediate the targeting of other mitochondrial preproteins, they were found to resemble presequences in their strict dependence on a content of positively charged residues as a prerequisite of interactions with the import pore. Conclusions: The general import pore of the mitochondrial outer membrane appears to represent not only the central channel of protein translocation but also to form the decisive general selectivity filter in the uptake of the newly synthesized mitochondrial proteins. Keywords: Mitochondria, Protein targeting, TOM complex, Tom40, Tom70, Chaperones, Ion channel, Selectivity filter
Background Mitochondria developed in evolution from independent organisms, but within the eukaryotic cells, their growth and their activity are dependent on an intensive exchange of metabolites with the surrounding cytosol. The transport of most of these metabolites is mediated by a large group of related proteins of the mitochondrial inner membrane, the members of the mitochondrial carrier family, MCF (corresponding to the solute carrier family 25, SLC25). In the human genome, 53 genes * Correspondence: [email protected] † Sebastian Kreimendahl and Jan Schwichtenberg contributed equally to this work. Institute for Biochemistry and Pathobiochemistry, Ruhr-University Bochum, 44780 Bochum, Germany
encoding proteins of this family were identified; 35 MCF genes were found in the yeast Saccharomyces cerevisiae [1–4]. Each of the encoded proteins is specific for a small subset of the metabolites. Besides metabolites, also proteins are transported ac
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