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EMBO reports AOP
doi:10.1038/embor.2008.49
Published online: 18 April 2008
Assembly of the three small Tim proteins precedes docking to the mitochondrial carrier translocase
Natalia Gebert1, 2, Agnieszka Chacinska1, Karina Wagner1, 2, Bernard Guiard3, Carla M Koehler4, Peter Rehling1, 5, Nikolaus Pfanner1 & Nils Wiedemann1
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1 Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung, Universität Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany
2 Fakultät für Biologie, Universität Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany
3 Centre de Génétique Moléculaire, CNRS, 91190 Gif-sur-Yvette, France
4 Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095-1569, USA
5 Abteilung Biochemie II, Universität Göttingen, 37073 Göttingen, Germany
To whom correspondence should be addressed
Nikolaus Pfanner Tel: +49 761 203 5224; Fax: +49 761 203 5261; E-mail: nikolaus.pfanner@biochemie.uni-freiburg.de
Received 23 November 2007; Accepted 3 March 2008; Published online 18 April 2008.
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Abstract
The mitochondrial intermembrane space contains a family of small Tim proteins that function as essential chaperones for protein import. The soluble Tim9–Tim10 complex transfers hydrophobic precursor proteins through the aqueous intermembrane space to the carrier translocase of the inner membrane (TIM22 complex). Tim12, a peripheral membrane subunit of the TIM22 complex, is thought to recruit a portion of Tim9–Tim10 to the inner membrane. It is not known, however, how Tim12 is assembled. We have identified a new intermediate in the biogenesis pathway of Tim12. A soluble form of Tim12 first assembles with Tim9 and Tim10 to form a Tim12-core complex. Tim12-core then docks onto the membrane-integrated subunits of the TIM22 complex to form the holo-translocase. Thus, the function of Tim12 in linking soluble and membrane-integrated subunits of the import machinery involves a sequential assembly mechanism of the translocase through a soluble intermediate complex of the three essential small Tim proteins.
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