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cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation.

BMC cell biology | Nov 25, 2010

BACKGROUND: Appropriate control of mitochondrial function, morphology and biogenesis are crucial determinants of the general health of eukaryotic cells. It is therefore imperative that we understand the mechanisms that co-ordinate mitochondrial function with environmental signaling systems. The regulation of yeast mitochondrial function in response to nutritional change can be modulated by PKA activity. Unregulated PKA activity can lead to the production of mitochondria that are prone to the production of ROS, and an apoptotic form of cell death. RESULTS: We present evidence that mitochondria are sensitive to the level of cAMP/PKA signaling and can respond by modulating levels of respiratory activity or committing to self execution. The inappropriate activation of one of the yeast PKA catalytic subunits, Tpk3p, is sufficient to commit cells to an apoptotic death through transcriptional changes that promote the production of dysfunctional, ROS producing mitochondria. Our data implies that cAMP/PKA regulation of mitochondrial function that promotes apoptosis engages the function of multiple transcription factors, including HAP4, SOK2 and SCO1. CONCLUSIONS: We propose that in yeast, as is the case in mammalian cells, mitochondrial function and biogenesis are controlled in response to environmental change by the concerted regulation of multiple transcription factors. The visualization of cAMP/TPK3 induced cell death within yeast colonies supports a model that PKA regulation plays a physiological role in coordinating respiratory function and cell death with nutritional status in budding yeast.

Pubmed ID: 21108829 RIS Download

Mesh terms: Apoptosis | CCAAT-Binding Factor | Catalytic Domain | Cyclic AMP | Cyclic AMP-Dependent Protein Kinase Catalytic Subunits | Cyclic AMP-Dependent Protein Kinases | Gene Expression Regulation, Fungal | Membrane Proteins | Mitochondria | Mitochondrial Proteins | Reactive Oxygen Species | Repressor Proteins | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Signal Transduction | Transcription Factors

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Associated grants

  • Agency: Medical Research Council, Id: MRC_G0600085
  • Agency: Medical Research Council, Id:

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SGD Gene Ontology Slim Mapper

The GO Slim Mapper (aka GO Term Mapper) maps the specific, granular GO terms used to annotate a list of budding yeast gene products to corresponding more general parent GO slim terms. Uses the SGD GO Slim sets. Three GO Slim sets are available at SGD: * Macromolecular complex terms: protein complex terms from the Cellular Component ontology * Yeast GO-Slim: GO terms that represent the major Biological Processes, Molecular Functions, and Cellular Components in S. cerevisiae * Generic GO-Slim: broad, high level GO terms from the Biological Process and Cellular Component ontologies selected and maintained by the Gene Ontology Consortium (GOC) Platform: Online tool

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Yeast Search for Transcriptional Regulators And Consensus Tracking

A curated repository of more than 206000 regulatory associations between transcription factors (TF) and target genes in Saccharomyces cerevisiae, based on more than 1300 bibliographic references. It also includes the description of 326 specific DNA binding sites shared among 113 characterized TFs. Further information about each Yeast gene has been extracted from the Saccharomyces Genome Database (SGD). For each gene the associated Gene Ontology (GO) terms and their hierarchy in GO was obtained from the GO consortium. Currently, YEASTRACT maintains a total of 7130 terms from GO. The nucleotide sequences of the promoter and coding regions for Yeast genes were obtained from Regulatory Sequence Analysis Tools (RSAT). All the information in YEASTRACT is updated regularly to match the latest data from SGD, GO consortium, RSA Tools and recent literature on yeast regulatory networks. YEASTRACT includes DISCOVERER, a set of tools that can be used to identify complex motifs found to be over-represented in the promoter regions of co-regulated genes. DISCOVERER is based on the MUSA algorithm. These algorithms take as input a list of genes and identify over-represented motifs, which can then be compared with transcription factor binding sites described in the YEASTRACT database.

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