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Originally published In Press as doi:10.1074/jbc.M412269200 on December 16, 2004 Originally published In Press as doi:10.1074/jbc.M412269200 on December 9, 2004

J. Biol. Chem., Vol. 280, Issue 7, 6215-6221, February 18, 2005
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The Carboxyl-terminal Third of the Dicarboxylate Carrier Is Crucial for Productive Association with the Inner Membrane Twin-pore Translocase*

Katrin Brandner{ddagger}, Peter Rehling{ddagger}, and Kaye N. Truscott{ddagger}§

From the {ddagger}Institut für Biochemie und Molekularbiologie, Universität Freiburg, D-79104 Freiburg, Germany and the §Department of Biochemistry, La Trobe University, 3086 Melbourne, Victoria, Australia

The carrier proteins of the mitochondrial inner membrane consist of three structurally related tandem repeats (modules). Several different, and in some cases contradictory, views exist on the role individual modules play in carrier transport across the mitochondrial membranes and how they promote protein insertion into the inner membrane. Thus, by use of specific translocation intermediates, we performed a detailed analysis of carrier biogenesis and assessed the physical association of carrier modules with the inner membrane translocation machinery. Here we have reported that each module of the dicarboxylate carrier contains sufficient targeting information for its transport across the outer mitochondrial membrane. The carboxyl-terminal module possesses major targeting information to facilitate the direct binding of the carrier protein to the inner membrane twin-pore translocase and subsequent insertion into the inner membrane in a membrane potential-dependent manner. We concluded that, in this case, a single structural repeat can drive inner membrane insertion, whereas all three related units contribute targeting information for outer membrane translocation.


Received for publication, October 29, 2004 , and in revised form, December 8, 2004.

* This work was supported by the Australian Research Council (to K. N. T.) and the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 388. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 61-3-9479-3276; Fax: 61-3-9479-2467; E-mail: K.Truscott{at}latrobe.edu.au.


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