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Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5

Nature volume 391, pages 912–915 (1998)Cite this article

Abstract

Import of nuclear-encoded precursor proteins into mitochondria and their subsequent sorting into mitochondrial subcompartments is mediated by translocase enzymes in the mitochondrial outer and inner membranes1,2,3. Precursor proteins carrying amino-terminal targeting signals are translocated into the matrix by the integral inner membrane proteins Tim23 and Tim17 in cooperation with Tim44 and mitochondrial Hsp70 (4-7). We describe here the discovery of a new pathway for the transport of members of the mitochondrial carrier family and other inner membrane proteins that contain internal targeting signals. Two related proteins in the intermembrane space, Tim10/Mrs11 (ref. 8) and Tim12/Mrs5 (ref. 9), interact sequentially with these precursors and facilitate their translocation across the outer membrane, irrespective of the membrane potential. Tim10 and Tim12 are found in a complex with Tim22, which takes over the precursor and mediates its membrane-potential-dependent insertion into the inner membrane. This interaction of Tim10 and Tim12 with the precursors depends on the presence of divalent metal ions. Both proteins contain a zinc-finger-like motif with four cysteines and bind equimolar amounts of zinc ions.

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Figure 1: Association of Tim12 and Tim10 with the inner membrane.
Figure 2: Tim10 and Tim12 facilitate import of carrier proteins and of Tim22.
Figure 3: Requirement for divalent cations.
Figure 4: Zn2+ content of Tim12 and Tim10 fusion proteins.

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Acknowledgements

We thank M. Zenk for determination of zinc by AAS. This work was supported by grants from the Deutsche Forschungsgemeinschaft, the Human Frontiers of Science Program, the Fonds der Chemischen Industrie and the Münchener Medizinische Wochenschrift (to R.A.S. and to M.B.)

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  1. Institut für Physiologische Chemie der Universität München, Goethestraβe 33, 80336, München, Germany

    Christian Sirrenberg, Maxi Endres, Heike Fölsch, Rosemary A. Stuart, Walter Neupert & Michael Brunner

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  1. Christian Sirrenberg
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  6. Michael Brunner
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Correspondence to Walter Neupert.

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Sirrenberg, C., Endres, M., Fölsch, H. et al. Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5. Nature 391, 912–915 (1998). https://doi.org/10.1038/36136

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