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Comp Funct Genomics. Feb 2003; 4(1): 37–46.
PMCID: PMC2447382

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

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.

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Selected References

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  • Betina S, Gavurníková G, Haviernik P, Sabová L, Kolarov J. Expression of the AAC2 gene encoding the major mitochondrial ADP/ATP carrier in Saccharomyces cerevisiae is controlled at the transcriptional level by oxygen, heme and HAP2 factor. Eur J Biochem. 1995 May 1;229(3):651–657. [PubMed]
  • Blom J, De Mattos MJ, Grivell LA. Redirection of the respiro-fermentative flux distribution in Saccharomyces cerevisiae by overexpression of the transcription factor Hap4p. Appl Environ Microbiol. 2000 May;66(5):1970–1973. [PMC free article] [PubMed]
  • Bourgarel D, Nguyen CC, Bolotin-Fukuhara M. HAP4, the glucose-repressed regulated subunit of the HAP transcriptional complex involved in the fermentation-respiration shift, has a functional homologue in the respiratory yeast Kluyveromyces lactis. Mol Microbiol. 1999 Feb;31(4):1205–1215. [PubMed]
  • Breunig KD. Glucose repression of LAC gene expression in yeast is mediated by the transcriptional activator LAC9. Mol Gen Genet. 1989 Apr;216(2-3):422–427. [PubMed]
  • Bryan Anthony C, Rodeheffer Matthew S, Wearn Christopher M, Shadel Gerald S. Sls1p is a membrane-bound regulator of transcription-coupled processes involved in Saccharomyces cerevisiae mitochondrial gene expression. Genetics. 2002 Jan;160(1):75–82. [PMC free article] [PubMed]
  • Church C, Poyton RO. Neither respiration nor cytochrome c oxidase affects mitochondrial morphology in Saccharomyces cerevisiae. J Exp Biol. 1998 Jun;201(Pt 11):1729–1737. [PubMed]
  • de Winde JH, Grivell LA. Global regulation of mitochondrial biogenesis in Saccharomyces cerevisiae. Prog Nucleic Acid Res Mol Biol. 1993;46:51–91. [PubMed]
  • Dang VD, Valens M, Bolotin-Fukuhara M, Daignan-Fornier B. A genetic screen to isolate genes regulated by the yeast CCAAT-box binding protein Hap2p. Yeast. 1994 Oct;10(10):1273–1283. [PubMed]
  • DeRisi JL, Iyer VR, Brown PO. Exploring the metabolic and genetic control of gene expression on a genomic scale. Science. 1997 Oct 24;278(5338):680–686. [PubMed]
  • Fairhead C, Thierry A, Denis F, Eck M, Dujon B. 'Mass-murder' of ORFs from three regions of chromosome XI from Saccharomyces cerevisiae. Gene. 1998 Nov 26;223(1-2):33–46. [PubMed]
  • Ferea TL, Botstein D, Brown PO, Rosenzweig RF. Systematic changes in gene expression patterns following adaptive evolution in yeast. Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9721–9726. [PMC free article] [PubMed]
  • Freire-Picos MA, Hollenberg CP, Breunig KD, Cerdan ME. Regulation of cytochrome c expression in the aerobic respiratory yeast Kluyveromyces lactis. FEBS Lett. 1995 Feb 20;360(1):39–42. [PubMed]
  • Ferrero I, Rossi C, Landini MP, Puglisi PP. Role of the mitochondrial protein synthesis is the catabolite repression of the petite-negative yeast K.lactis. Biochem Biophys Res Commun. 1978 Jan 30;80(2):340–348. [PubMed]
  • Forsburg SL, Guarente L. Communication between mitochondria and the nucleus in regulation of cytochrome genes in the yeast Saccharomyces cerevisiae. Annu Rev Cell Biol. 1989;5:153–180. [PubMed]
  • Forsburg SL, Guarente L. Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer. Genes Dev. 1989 Aug;3(8):1166–1178. [PubMed]
  • Gavurníková G, Sabova L, Kissová I, Haviernik P, Kolarov J. Transcription of the AAC1 gene encoding an isoform of mitochondrial ADP/ATP carrier in Saccharomyces cerevisiae is regulated by oxygen in a heme-independent manner. Eur J Biochem. 1996 Aug 1;239(3):759–763. [PubMed]
  • Green-Willms NS, Butler CA, Dunstan HM, Fox TD. Pet111p, an inner membrane-bound translational activator that limits expression of the Saccharomyces cerevisiae mitochondrial gene COX2. J Biol Chem. 2001 Mar 2;276(9):6392–6397. [PubMed]
  • Haselbeck RJ, McAlister-Henn L. Function and expression of yeast mitochondrial NAD- and NADP-specific isocitrate dehydrogenases. J Biol Chem. 1993 Jun 5;268(16):12116–12122. [PubMed]
  • Hauser NC, Vingron M, Scheideler M, Krems B, Hellmuth K, Entian KD, Hoheisel JD. Transcriptional profiling on all open reading frames of Saccharomyces cerevisiae. Yeast. 1998 Sep 30;14(13):1209–1221. [PubMed]
  • Keng T, Richard C, Larocque R. Structure and regulation of yeast HEM3, the gene for porphobilinogen deaminase. Mol Gen Genet. 1992 Aug;234(2):233–243. [PubMed]
  • Keng T, Guarente L. Constitutive expression of the yeast HEM1 gene is actually a composite of activation and repression. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9113–9117. [PMC free article] [PubMed]
  • Liu Z, Butow RA. A transcriptional switch in the expression of yeast tricarboxylic acid cycle genes in response to a reduction or loss of respiratory function. Mol Cell Biol. 1999 Oct;19(10):6720–6728. [PMC free article] [PubMed]
  • Lodi T, Goffrini P, Bolondi I, Ferrero I. Transcriptional regulation of the KlDLD gene, encoding the mitochondrial enzyme D-lactate ferricytochrome c oxidoreductase in Kluyveromyces lactis: effect of Klhap2 and fog mutations. Curr Genet. 1998 Jul;34(1):12–20. [PubMed]
  • Mulder W, Scholten IH, de Boer RW, Grivell LA. Sequence of the HAP3 transcription factor of Kluyveromyces lactis predicts the presence of a novel 4-cysteine zinc-finger motif. Mol Gen Genet. 1994 Oct 17;245(1):96–106. [PubMed]
  • Mulder W, Scholten IH, Grivell LA. Distinct transcriptional regulation of a gene coding for a mitochondrial protein in the yeasts Saccharomyces cerevisiae and Kluyveromyces lactis despite similar promoter structures. Mol Microbiol. 1995 Sep;17(5):813–824. [PubMed]
  • Nguyen C, Bolotin-Fukuhara M, Wésolowski-Louvel M, Fukuhara H. The respiratory system of Kluyveromyces lactis escapes from HAP2 control. Gene. 1995 Jan 11;152(1):113–115. [PubMed]
  • Rassow J, Voos W, Pfanner N. Partner proteins determine multiple functions of Hsp70. Trends Cell Biol. 1995 May;5(5):207–212. [PubMed]
  • Sokolíková B, Sabová L, Kissová I, Kolarov J. A carbon-source-responsive element is required for regulation of the hypoxic ADP/ATP carrier (AAC3) isoform in Saccharomyces cerevisiae. Biochem J. 2000 Dec 15;352(Pt 3):893–898. [PMC free article] [PubMed]
  • Theilhaber J, Bushnell S, Jackson A, Fuchs R. Bayesian estimation of fold-changes in the analysis of gene expression: the PFOLD algorithm. J Comput Biol. 2001;8(6):585–614. [PubMed]
  • Traven Ana, Staresincić Lidija, Arnerić Milica, Sopta Mary. The yeast protein Xtc1 functions as a direct transcriptional repressor. Nucleic Acids Res. 2002 Jun 1;30(11):2358–2364. [PMC free article] [PubMed]
  • Wach A, Brachat A, Pöhlmann R, Philippsen P. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994 Dec;10(13):1793–1808. [PubMed]

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