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Tom22 is a multifunctional organizer of the mitochondrial preprotein translocase

Nature volume 401, pages 485–489 (1999)Cite this article

An Erratum to this article was published on 30 November 2000

Abstract

Mitochondrial preproteins are imported by a multisubunit translocase of the outer membrane (TOM), including receptor proteins and a general import pore1,2,3,4,5. The central receptor Tom22 binds preproteins through both its cytosolic domain and its intermembrane space domain6,7,8,9,10 and is stably associated with the channel protein Tom40 (refs 11,12,13). Here we report the unexpected observation that a yeast strain can survive without Tom22, although it is strongly reduced in growth and the import of mitochondrial proteins. Tom22 is a multifunctional protein that is required for the higher-level organization of the TOM machinery. In the absence of Tom22, the translocase dissociates into core complexes, representing the basic import units, but lacks a tight control of channel gating. The single membrane anchor of Tom22 is required for a stable interaction between the core complexes, whereas its cytosolic domain serves as docking point for the peripheral receptors Tom20 and Tom70. Thus a preprotein translocase can combine receptor functions with distinct organizing roles in a multidomain protein.

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Figure 1: A yeast strain lacking TOM22.
Figure 2: Inhibition of preprotein import into tom22Δ mitochondria.
Figure 3: Tom22 as a docking point for Tom20 and Tom70.
Figure 4: Lack of Tom22 causes dissociation of the 400K GIP complex.
Figure 5: Increased open probability of the import channel of tom22Δ mitochondria.

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Acknowledgements

We thank M. Jacquet, T. Lithgow and T. Krimmer for materials and discussion, and H. Müller for technical assistance. This work was supported by the Sonderforschungsbereich 388, the Fonds der Chemischen Industrie (N.P.), the Sonderforschungsbereich 431 (R.W.) and long-term fellowships of the Alexander-von-Humboldt Foundation (M.T.R.) and the Human Frontier Science Program (P.J.T.D.).

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Author notes

  1. Sandra van Wilpe and Michael T. Ryan: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute for Molecular Cell Biology, BioCentrum Amsterdam, Amsterdam, 1098 SM, The Netherlands

    Sandra van Wilpe, Ammy C. Maarse & Michiel Meijer

  2. Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Strasse 7, Freiburg, 79104, Germany

    Michael T. Ryan, Chris Meisinger, Jan Brix, Peter J. T. Dekker, Martin Moczko, Angelika Hönlinger & Nikolaus Pfanner

  3. Biophysik, Universität Osnabrück, FB Biologie/Chemie, Osnabrück, 49034, Germany

    Kerstin Hill & Richard Wagner

  4. Centre de Génétique Moleculaire CNRS, Université Pierre et Marie Curie, Gif-sur-Yvette, 91190, France

    Bernard Guiard

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Correspondence to Nikolaus Pfanner.

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van Wilpe, S., Ryan, M., Hill, K. et al. Tom22 is a multifunctional organizer of the mitochondrial preprotein translocase. Nature 401, 485–489 (1999). https://doi.org/10.1038/46802

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