Papers In Press, published online ahead of print June 20, 2005
J. Biol. Chem, 10.1074/jbc.M505915200
Submitted on May 31, 2005
Accepted on June 20, 2005
Effect of inhibition of the BC1 complex on gene expression profile in yeast
Ingrid Bourges, Susannah Horan, and Brigitte Meunier
Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT
Corresponding Author: b.meunier{at}ucl.ac.uk
As 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 programme 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 were found to decreased 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.