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J. Biol. Chem., Vol. 280, Issue 33, 29743-29749, August 19, 2005

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Effect of Inhibition of the bc₁ Complex on Gene Expression Profile in Yeast^*

Ingrid Bourges, Susannah Horan, and Brigitte Meunier

From the Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom

Because the respiratory chain is the major site of oxidation of the reduced equivalents and of energy production in aerobic cells, its inhibition has severe impact on the cells. Communication pathways from the respiratory chain are required to allow the cell to sense the defect and respond to it. In this work, we studied changes in gene expression induced by the treatment of yeast cells with myxothiazol, an inhibitor of the bc₁ complex, an enzyme of the respiratory chain. The pattern and time-course expression of the genes resemble those of the environmental stress response, a common gene expression program induced by sudden changes in the environment. In addition, the changes were, for most of the genes, mediated through the transcription factors Msn2/4, which play a central role in the cellular response to these stresses. By using a mutant with a myxothiazol-resistant bc₁ complex, we showed that the changes of expression of the majority of the genes was caused by the inhibition of the bc₁ complex but that other stresses might be involved. The expression pattern of CTT1, coding for a cytoplasmic catalase, was further studied. The expression of this gene was largely dependent on Msn2/4 and the inhibition of the cytochrome bc₁. Addition of oxidants of NADH was found to decrease the expression of CTT1 induced by myxothiazol treatment, suggesting that the accumulation of NADH caused by the inhibition of the respiratory chain may be involved in the signaling pathway from the mitochondria to the transcription factor.

Received for publication, May 31, 2005

^* This work was supported by a Medical Research Council Fellowship (to B. M.). 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table SI.

To whom correspondence should be addressed. Tel.: 44-20-7679-6860; Fax: 44-20-7209-0470; E-mail: b.meunier{at}ucl.ac.uk.

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