Tom70 enhances mitochondrial preprotein import efficiency by binding to internal targeting sequences
Open Access
- 30 January 2018
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 217 (4), 1369-1382
- https://doi.org/10.1083/jcb.201708044
Abstract
The biogenesis of mitochondria depends on the import of hundreds of preproteins. N-terminal matrix-targeting signals (MTSs) direct preproteins to the surface receptors Tom20, Tom22, and Tom70. In this study, we show that many preproteins contain additional internal MTS-like signals (iMTS-Ls) in their mature region that share the characteristic properties of presequences. These features allow the in silico prediction of iMTS-Ls. Using Atp1 as model substrate, we show that iMTS-Ls mediate the binding to Tom70 and have the potential to target the protein to mitochondria if they are presented at its N terminus. The import of preproteins with high iMTS-L content is significantly impaired in the absence of Tom70, whereas preproteins with low iMTS-L scores are less dependent on Tom70. We propose a stepping stone model according to which the Tom70-mediated interaction with internal binding sites improves the import competence of preproteins and increases the efficiency of their translocation into the mitochondrial matrix.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (He2803/9-1, IRTG 1830)
This publication has 89 references indexed in Scilit:
- Interaction between the Human Mitochondrial Import Receptors Tom20 and Tom70 in Vitro Suggests a Chaperone Displacement MechanismPublished by Elsevier BV ,2011
- In vivo protein-interaction mapping of a mitochondrial translocator protein Tom22 at workProceedings of the National Academy of Sciences of the United States of America, 2011
- Dual role of the receptor Tom20 in specificity and efficiency of protein import into mitochondriaProceedings of the National Academy of Sciences of the United States of America, 2010
- Substrate specificity of the TIM22 mitochondrial import pathway revealed with small molecule inhibitor of protein translocationProceedings of the National Academy of Sciences of the United States of America, 2010
- Structural basis for unfolding pathway-dependent stability of proteins: Vectorial unfolding versus global unfoldingProtein Science, 2010
- Roles of Tom70 in Import of Presequence-containing Mitochondrial ProteinsJournal of Biological Chemistry, 2009
- Molecular Chaperone Hsp70/Hsp90 Prepares the Mitochondrial Outer Membrane Translocon Receptor Tom71 for Preprotein LoadingPublished by Elsevier BV ,2009
- Tetratricopeptide repeat proteins Tom70 and Tom71 mediate yeast mitochondrial morphogenesisEMBO Reports, 2007
- Locating proteins in the cell using TargetP, SignalP and related toolsNature Protocols, 2007
- Rules for Nuclear Localization Sequence Recognition by Karyopherinβ2Cell, 2006