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Originally published In Press as doi:10.1074/jbc.M203834200 on June 26, 2002

J. Biol. Chem., Vol. 277, Issue 37, 33664-33669, September 13, 2002
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Tubulin Is an Inherent Component of Mitochondrial Membranes That Interacts with the Voltage-dependent Anion Channel*

Manon CarréDagger §, Nicolas AndréDagger §, Gérard CarlesDagger , Hélène Borghi||, Laetitia Brichese**, Claudette BriandDagger , and Diane BraguerDagger Dagger Dagger

From the Dagger  UMR CNRS 6032, UFR Pharmacy and the || Department of Electron Microscopy, UFR Medicine, University of La Méditerranée, 27 Boulevard Jean Moulin, 13005 Marseille, France and ** CNRS 2079, University Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse Cedex, France

We have previously reported that anti-tubulin agents induce the release of cytochrome c from isolated mitochondria. In this study, we show that tubulin is present in mitochondria isolated from different human cancerous and non-cancerous cell lines. The absence of polymerized microtubules and cytosolic proteins was checked to ensure that this tubulin is an inherent component of the mitochondria. In addition, a salt wash did not release the tubulin from the mitochondria. By using electron microscopy, we then showed that tubulin is localized in the mitochondrial membranes. As compared with cellular tubulin, mitochondrial tubulin is enriched in acetylated and tyrosinated alpha -tubulin and is also enriched in the class III beta -tubulin isotype but contains very little of the class IV beta -tubulin isotype. The mitochondrial tubulin is likely to be organized in alpha /beta dimers and represents 2.2 ± 0.5% of total cellular tubulin. Lastly, we showed by immunoprecipitation experiments that the mitochondrial tubulin is specifically associated with the voltage-dependent anion channel, the main component of the permeability transition pore. Thus, tubulin is an inherent component of mitochondrial membranes, and it could play a role in apoptosis via interaction with the permeability transition pore.


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ These authors contributed equally to this work.

Recipient of a fellowship from the Association pour la Recherche sur le Cancer.

Dagger Dagger To whom correspondence should be addressed. Tel.: 33-4-91-83-56-35; Fax: 33-4-91-78-20-24; E-mail: diane.braguer@pharmacie.univ.mrs.fr.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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