Predictable internal targeting signal-like sequences serve as Tom70 recognition sites in mitochondrial preproteins Sandra Backes1#, Steffen Hess1#, Felix Boos1, Michael W. Woellhaf1, Sabrina Gödel2, Martin Jung3, Timo Mühlhaus2*, Johannes M. Herrmann1* #, authors contributed equally 1, Cell Biology, University of Kaiserslautern, 67663 Kaiserslautern, Germany 2, Computational Systems Biology, University of Kaiserslautern, 67663 Kaiserslautern, Germany 3, Medical Biochemistry, Saarland University, 66421 Homburg, Germany
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. Here we show that many preproteins contain additional internal MTS-like signals (iMTS-Ls) in their mature region sharing the characteristic properties of presequences. These features allow the in silico prediction of iMTSs. Using Atp1 as model substrate, we show that iMTSs 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 content is significantly impaired in the absence of Tom70 whereas preproteins with low iMTS scores were 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.
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