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Science 9 June 2006:
Vol. 312. no. 5779, pp. 1523 - 1526
DOI: 10.1126/science.1127628
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Reports

Tim50 Maintains the Permeability Barrier of the Mitochondrial Inner Membrane

Michael Meinecke,1 Richard Wagner,1* Peter Kovermann,1{dagger} Bernard Guiard,2 David U. Mick,3 Dana P. Hutu,3,4 Wolfgang Voos,3 Kaye N. Truscott,3,5 Agnieszka Chacinska,3 Nikolaus Pfanner,3* Peter Rehling3

Transport of metabolites across the mitochondrial inner membrane is highly selective, thereby maintaining the electrochemical proton gradient that functions as the main driving force for cellular adenosine triphosphate synthesis. Mitochondria import many preproteins via the presequence translocase of the inner membrane. However, the reconstituted Tim23 protein constitutes a pore remaining mainly in its open form, a state that would be deleterious in organello. We found that the intermembrane space domain of Tim50 induced the Tim23 channel to close. Presequences overcame this effect and activated the channel for translocation. Thus, the hydrophilic cis domain of Tim50 maintains the permeability barrier of mitochondria by closing the translocation pore in a presequence-regulated manner.

1 Biophysik, Universität Osnabrück, FB Biologie/Chemie, D-49034 Osnabrück, Germany.
2 Centre de Génétique Moléculaire, Laboratoire propre du CNRS, F-91190 Gif-sur-Yvette, France.
3 Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Straße 7, D-79104 Freiburg, Germany.
4 Fakultät für Biologie, Universität Freiburg, Schänzlestraße 1, D-79104 Freiburg, Germany.
5 Department of Biochemistry, La Trobe University, Melbourne 3086, Australia.

{dagger} Present address: Institute for Plant Biology, Molecular Physiology, University of Zürich, 8008 Zürich, Switzerland.

* To whom correspondence should be addressed. E-mail: wagner{at}biologie.uni-osnabrueck.de (R.W.); nikolaus.pfanner{at}biochemie.uni-freiburg.de (N.P.)

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