Article thumbnail

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

By S. Buschlen, J-M Amillet, B. Guiard, A. Fournier, C. Marcireau and M. Bolotin-Fukuhara

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

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:2447382
Provided by: PubMed Central

Suggested articles

Citations

  1. (2000). A carbonsource-responsive element is required for regulation of the hypoxic ADP/ATP carrier (AAC3) isoform in Saccharomyces cerevisiae.
  2. (1994). A genetic screen to isolate genes regulated by the yeast CCAAT-box binding protein Hap2p.
  3. (1999). A transcriptional switch in the expression of yeast tricarboxylic acid cycle genes in response to a reduction or loss of respiratory function.
  4. (2001). Bayesian estimation of fold-changes in the analysis of gene expression: the PFOLD algorithm.
  5. (1989). Communication between mitochondria and the nucleus in regulation of cytochrome genes in the yeast Saccharomyces cerevisiae.
  6. (1987). Constitutive expression of the yeast HEM1 gene is actually a composite of activation and repression.
  7. (1995). Distinct transcriptional regulation of a gene coding for a mitochondrial protein in the yeasts Saccharomyces cerevisiae and Kluyveromyces lactis despite similar promoter structures.
  8. (1997). Exploring the metabolic and genetic control of gene expression on a genomic scale.
  9. (1995). 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.
  10. (1993). Function and expression of yeast mitochondrial NAD- and NADP-specific isocitrate dehydrogenases.
  11. (1993). Global regulation of mitochondrial biogenesis in Saccharomyces cerevisiae.
  12. (1989). Glucose repression of LAC gene expression in yeast is mediated by the transcriptional activator LAC9.
  13. (1999). HAP4,t h e 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.
  14. (1989). Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer.
  15. (1998). Massmurder’ of ORFs from three regions of chromosome XI from Saccharomyces cerevisiae.
  16. (1998). Neither respiration nor cytochrome c oxidase affects mitochondrial morphology in Saccharomyces cerevisiae. JE x pB i o l201:
  17. (1994). New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae.
  18. (1995). Partner proteins determine multiple functions of Hsp70.
  19. (2001). Pet111p, an inner membrane-bound translational activator that limits expression of the Saccharomyces cerevisiae mitochondrial COX2. JB i o lC h e m276:
  20. (2000). Redirection of the respiro-fermentative flux distribution in Saccharomyces cerevisiae by overexpression of the transcription factor Hap4p.
  21. (1995). Regulation of cytochrome c expression in the aerobic respiratory yeast Kluyveromyces lactis.
  22. (1978). Role of the mitochondrial protein synthesis in the catabolite repression of the petite negative yeast Kluyveromyces lactis.
  23. (1994). Sequence of the HAP3 transcription factor of Kluyveromyces lactis predicts the presence of a novel 4-cysteine zinc-finger motif.
  24. (2002). Sls1p is a membrane-bound regulator of transcription-coupled processes involved in Saccharomyces cerevisiae mitochondrial gene expression.
  25. (1992). Structure and regulation of yeast HEM3, the gene for porphobilinogen deaminase.
  26. (1999). Systematic changes in gene expression patterns following adaptive evolution in yeast.
  27. (1994). The respiratory system of Kluyveromyces lactis escapes from HAP2 control.
  28. (2002). The yeast protein Xtc1p functions as a direct transcriptional repressor.
  29. (1996). 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.
  30. (1998). Transcriptional profiling on all open reading frames of Saccharomyces cerevisiae.
  31. (1998). Transcriptional regulation of the KlDLD gene, encoding the mitochondrial enzyme D-lactate ferricytochrome c oxidoreductase in Kluyveromyces lactis: effect of Klhap2 and fog mutations.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.