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      Recruitment of Cytosolic J-Proteins by TOM Receptors Promotes Mitochondrial Protein Biogenesis

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Mitochondria possess elaborate machineries for the import of proteins from the cytosol. Cytosolic factors like Hsp70 chaperones and their co-chaperones, the J-proteins, guide proteins to the mitochondrial surface. The translocase of the mitochondrial outer membrane (TOM) forms the entry gate for preproteins. How the proteins are delivered to mitochondrial preprotein receptors is poorly understood. We identify the cytosolic J-protein Xdj1 as a specific interaction partner of the central receptor Tom22. Tom22 recruits Xdj1 to the mitochondrial surface to promote import of preproteins and assembly of the TOM complex. Additionally, we find that the receptor Tom70 binds a different cytosolic J-protein, Djp1. Our findings suggest that cytosolic J-proteins target distinct TOM receptors and promote the biogenesis of mitochondrial proteins.

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          Highlights

          • The receptor Tom22 recruits the cytosolic J-protein Xdj1 to mitochondria

          • Xdj1 delivers preproteins to Tom22 and promotes biogenesis of the TOM complex

          • The receptor Tom70 recruits a different cytosolic J-protein, Djp1

          • Mitochondrial receptors selectively recognize cytosolic J-protein co-chaperones

          Abstract

          Opaliński et al. report that mitochondrial protein import receptors selectively recognize J-protein co-chaperones of the cytosol. The co-chaperones bind hydrophobic precursor proteins and assist in transferring them to the receptors of the mitochondrial protein entry gate.

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          Most cited references26

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          Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics.

          Quantitative proteomics has traditionally been performed by two-dimensional gel electrophoresis, but recently, mass spectrometric methods based on stable isotope quantitation have shown great promise for the simultaneous and automated identification and quantitation of complex protein mixtures. Here we describe a method, termed SILAC, for stable isotope labeling by amino acids in cell culture, for the in vivo incorporation of specific amino acids into all mammalian proteins. Mammalian cell lines are grown in media lacking a standard essential amino acid but supplemented with a non-radioactive, isotopically labeled form of that amino acid, in this case deuterated leucine (Leu-d3). We find that growth of cells maintained in these media is no different from growth in normal media as evidenced by cell morphology, doubling time, and ability to differentiate. Complete incorporation of Leu-d3 occurred after five doublings in the cell lines and proteins studied. Protein populations from experimental and control samples are mixed directly after harvesting, and mass spectrometric identification is straightforward as every leucine-containing peptide incorporates either all normal leucine or all Leu-d3. We have applied this technique to the relative quantitation of changes in protein expression during the process of muscle cell differentiation. Proteins that were found to be up-regulated during this process include glyceraldehyde-3-phosphate dehydrogenase, fibronectin, and pyruvate kinase M2. SILAC is a simple, inexpensive, and accurate procedure that can be used as a quantitative proteomic approach in any cell culture system.
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            A global genetic interaction network maps a wiring diagram of cellular function.

            We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell.
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              Translocation of proteins into mitochondria.

              About 10% to 15% of the nuclear genes of eukaryotic organisms encode mitochondrial proteins. These proteins are synthesized in the cytosol and recognized by receptors on the surface of mitochondria. Translocases in the outer and inner membrane of mitochondria mediate the import and intramitochondrial sorting of these proteins; ATP and the membrane potential are used as energy sources. Chaperones and auxiliary factors assist in the folding and assembly of mitochondrial proteins into their native, three-dimensional structures. This review summarizes the present knowledge on the import and sorting of mitochondrial precursor proteins, with a special emphasis on unresolved questions and topics of current research.
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                Author and article information

                Contributors
                Journal
                Cell Rep
                Cell Rep
                Cell Reports
                Cell Press
                2211-1247
                20 November 2018
                20 November 2018
                20 November 2018
                : 25
                : 8
                : 2036-2043.e5
                Affiliations
                [1 ]Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
                [2 ]Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany
                [3 ]Institute of Biology II, Biochemistry and Functional Proteomics, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany
                [4 ]BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany
                Author notes
                [5]

                Present address: Faculty of Biotechnology, Department of Protein Engineering, University of Wroclaw, 50-383 Wroclaw, Poland

                [6]

                Present address: Sanofi Deutschland GmbH, 65926 Frankfurt am Main, Germany

                [7]

                Lead Contact

                Article
                S2211-1247(18)31687-5
                10.1016/j.celrep.2018.10.083
                6280124
                30463002
                2d2a77cd-410c-40f5-9211-d18c23b73c56
                © 2018 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 26 November 2017
                : 19 September 2018
                : 24 October 2018
                Categories
                Article

                Cell biology
                mitochondria,tom complex,protein targeting,j-proteins,cytosolic chaperones
                Cell biology
                mitochondria, tom complex, protein targeting, j-proteins, cytosolic chaperones

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