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Comparative and Functional Genomics
Volume 4 (2003), Issue 1, Pages 37-46
http://dx.doi.org/10.1002/cfg.254
Conference Paper

The S. cerevisiae HAP Complex, a Key Regulator of Mitochondrial Function, Coordinates Nuclear and Mitochondrial Gene Expression

1Laboratoire de Génétique Moléculaire, IGM, Batiment 400. Université Paris Sud, 91405 Orsay Cedex, France
2Aventis Pharma, Core Biotechnology/Yeast Genomics. 13 Quai Jules Guesde, Vitry sur Seine 94403, France
3Centre de Génétique Moléculaire, Avenue de la Terrasse, Gif sur Yvette, 91198, France

Received 26 August 2002; Accepted 4 December 2002

Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We have compared Saccharomyces cerevisiae global gene expression in wild-type and mutants (Δhap2 and Δhap4) of the HAP transcriptional complex, which has been shown to be necessary for growth on respiratory substrates. Several hundred ORFs are under positive or negative control of this complex and we analyse here in detail the effect of HAP on mitochondria. We found that most of the genes upregulated in the wild-type strain were involved in organelle functions, but practically none of the downregulated ones. Nuclear genes encoding the different subunits of the respiratory chain complexes figure in the genes more expressed in the wild-type than in the mutants, as expected, but in this group we also found key components of the mitochondrial translation apparatus. This control of mitochondrial translation may be one of the means of coordinating mitochondrial and nuclear gene expression in elaborating the respiratory chain. In addition, HAP controls the nuclear genes involved in several other mitochondrial processes (import, mitochondrial division) that define the metabolic state of the cell, but not mitochondrial DNA replication and transcription. In most cases, a putative CCAAT-binding site is present upstream of the ORF, while in others no such sites are present, suggesting the control to be indirect. The large number of genes regulated by the HAP complex, as well as the fact that HAP also regulates some putative transcriptional activators of unknown function, place this complex at a hierarchically high position in the global transcriptional regulation of the cell.