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Molecular and Cellular Biology, July 2008, p. 4251-4260, Vol. 28, No. 13
0270-7306/08/$08.00+0 doi:10.1128/MCB.02216-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
The Assembly Pathway of the Mitochondrial Carrier Translocase Involves Four Preprotein Translocases
,
Karina Wagner,1,2
Natalia Gebert,1,2
Bernard Guiard,3
Katrin Brandner,1
Kaye N. Truscott,1,4
Nils Wiedemann,1
Nikolaus Pfanner,1* and
Peter Rehling1,5*
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, D-79104 Freiburg, Germany,1 Fakultät für Biologie, Universität Freiburg, D-79104 Freiburg, Germany,2 Centre de Génétique Moléculaire, CNRS, 91190 Gif-sur-Yvette, France,3 Department of Biochemistry, La Trobe University, Melbourne 3086, Australia,4 Abteilung für Biochemie II, Universität Göttingen, D-37073 Göttingen, Germany5
Received 14 December 2007/ Returned for modification 28 February 2008/ Accepted 25 April 2008
The mitochondrial inner membrane contains preprotein translocases that mediate insertion of hydrophobic proteins. Little is known about how the individual components of these inner membrane preprotein translocases combine to form multisubunit complexes. We have analyzed the assembly pathway of the three membrane-integral subunits Tim18, Tim22, and Tim54 of the twin-pore carrier translocase. Tim54 displayed the most complex pathway involving four preprotein translocases. The precursor is translocated across the intermembrane space in a supercomplex of outer and inner membrane translocases. The TIM10 complex, which translocates the precursor of Tim22 through the intermembrane space, functions in a new posttranslocational manner: in case of Tim54, it is required for the integration of Tim54 into the carrier translocase. Tim18, the function of which has been unknown so far, stimulates integration of Tim54 into the carrier translocase. We show that the carrier translocase is built via a modular process and that each subunit follows a different assembly route. Membrane insertion and assembly into the oligomeric complex are uncoupled for each precursor protein. We propose that the mitochondrial assembly machinery has adapted to the needs of each membrane-integral subunit and that the uncoupling of translocation and oligomerization is an important principle to ensure continuous import and assembly of protein complexes in a highly active membrane.
* Corresponding author. Mailing address for Nikolaus Pfanner: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, D-79104 Freiburg, Germany. Phone: 49-761-203-5224. Fax:49-761-203-5261. E-mail: nikolaus.pfanner{at}biochemie.uni-freiburg.de. Mailing address for Peter Rehling: Abteilung für Biochemie II, Universität Göttingen, Heinrich-Düker-Weg 12, D-37073 Göttingen, Germany. Phone: 49-551-39-5947. Fax: 49-551-39-5979. E-mail: peter.rehling{at}medizin.uni-goettingen.de
Published ahead of print on 5 May 2008.
Supplemental material for this article may be found at http://mcb.asm.org/.
Molecular and Cellular Biology, July 2008, p. 4251-4260, Vol. 28, No. 13
0270-7306/08/$08.00+0 doi:10.1128/MCB.02216-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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