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The J domain–related cochaperone Tim16 is a constituent of the mitochondrial TIM23 preprotein translocase

Nature Structural & Molecular Biology volume 11, pages 234–241 (2004)Cite this article

Abstract

Mitochondria import the vast majority of their proteins from the cytosol. The mitochondrial import motor of the TIM23 translocase drives the translocation of precursor proteins across the outer and inner membrane in an ATP-dependent reaction. Tim44 at the inner face of the translocation pore recruits the chaperone mtHsp70, which binds the incoming precursor protein. This reaction is assisted by the cochaperones Tim14 and Mge1. We have identified a novel essential cochaperone, Tim16. It is related to J-domain proteins and forms a stable subcomplex with the J protein Tim14. Depletion of Tim16 has a marked effect on protein import into the mitochondrial matrix, impairs the interaction of Tim14 with the TIM23 complex and leads to severe structural changes of the import motor. In conclusion, Tim16 is a constituent of the TIM23 preprotein translocase, where it exerts crucial functions in the import motor.

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Figure 1: The J-related protein Tim16 is present in a complex with Tim14.
Figure 2: Subcellular and submitochondrial localization of Tim16.
Figure 3: Import of preproteins by the TIM23 complex is affected in mitochondria depleted of Tim16.
Figure 4: Tim16 is a component of the TIM23 complex.
Figure 5: Tim16 is in close proximity to a translocating polypeptide chain.
Figure 6: Tim16 is part of the import motor.

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Acknowledgements

We are grateful to U. Gärtner, H. Germeroth and M. Malesic for excellent technical assistance, to T. Schwickert for help in some experiments, to A. Azem for providing the yeast strain expressing mtHsp70-His and to C. Bornhövd and S. Meier for providing subcellular yeast fractions and the CoxVa constructs. We thank A. Reichert for critically reading the manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 594 (B3, B4)), the Bundesministerium für Bildung und Forschung (MITOP) and the Fonds der Chemischen Industrie.

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  1. Christian Kozany and Dejana Mokranjac: These authors contributed equally to this work.

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  1. Institut für Physiologische Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5, München, 81377, Germany

    Christian Kozany, Dejana Mokranjac, Martin Sichting, Walter Neupert & Kai Hell

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Correspondence to Kai Hell.

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Kozany, C., Mokranjac, D., Sichting, M. et al. The J domain–related cochaperone Tim16 is a constituent of the mitochondrial TIM23 preprotein translocase. Nat Struct Mol Biol 11, 234–241 (2004). https://doi.org/10.1038/nsmb734

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