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Originally published In Press as doi:10.1074/jbc.C200551200 on October 2, 2002

J. Biol. Chem., Vol. 277, Issue 46, 43553-43556, November 15, 2002
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ACCELERATED PUBLICATION
Gluing the Respiratory Chain Together
CARDIOLIPIN IS REQUIRED FOR SUPERCOMPLEX FORMATION IN THE INNER MITOCHONDRIAL MEMBRANE*

Mei Zhang, Eugenia Mileykovskaya, and William DowhanDagger

From the Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, Texas 77225

Cytochrome bc1 complex (complex III) and cytochrome c oxidase complex (complex IV) are multisubunit homodimers that are essential components of the mitochondrial respiratory chain. Complexes III and IV associate to form a supercomplex that can be displayed using blue native polyacrylamide gel electrophoresis. Both homodimeric complexes contain tightly associated cardiolipin (CL) required for function. We report here that in a crd1Delta strain of yeast (null in expression of CL synthase) ~90% of complexes III and IV were observed as individual homodimers; only the supercomplex was observed with CRD1 wild type cells. Introduction of a plasmid born copy of the CRD1 gene under exogenous regulation by doxycycline made possible controlled variation in the in vivo CL levels. At an intermediate level of CL, a mixture of individual homodimers (30%) and supercomplex (70%) was observed. These results strongly indicate that CL plays a central role in higher order organization of components of the respiratory chain of mitochondria.

* This work was supported in part by National Institutes of Health Grant GM56389 (to W. D.).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.

Dagger To whom correspondence should be addressed: P. O. Box 20708, Dept. of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, TX 77225. Tel.: 713-500-6051; Fax: 713-500-0652; E-mail: William.Dowhan@uth.tmc.edu.

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


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