When transcriptome meets metabolome: fast cellular responses of yeast to sudden relief of glucose limitation

Kresnowati, Made Tri Ari Penia; Winden, Wouter A. van; Almering, Marinka J. H.; Pierick, Angela ten; Ras, Cor; Knijnenburg, Theo; Daran‐Lapujade, Pascale; Pronk, Jack T.; Heijnen, Joseph J.; Daran, Jean-Marc

doi:10.1038/msb4100083

Cited by 185 publications

(202 citation statements)

References 74 publications

(88 reference statements)

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“…In the yeast metabolic cycle, the methionine-regulated transcription factors exhibit the most highly periodic transcriptional activity, implying a connection between the methionine regulon and the respiro-fermentative balance (5)(6)(7). This implied connection is strengthened by a study of glucose repletion in yeast, which shows that methionine biosynthetic genes are highly induced upon relief from glucose starvation (8). The methionine-regulated transcription factors are also well known to regulate the response to various toxins, including heavy metals and oxidizing agents (9,10).…”

mentioning

confidence: 76%

Survival of starving yeast is correlated with oxidative stress response and nonrespiratory mitochondrial function

Petti

Crutchfield

Rabinowitz

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

103

120

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Survival of yeast during starvation has been shown to depend on the nature of the missing nutrient(s). In general, starvation for "natural" nutrients such as sources of carbon, phosphate, nitrogen, or sulfate results in low death rates, whereas starvation for amino acids or other metabolites in auxotrophic mutants results in rapid loss of viability. Here we characterized phenotype, gene expression, and metabolite abundance during starvation for methionine. Some methionine auxotrophs (those with blocks in the biosynthetic pathway) respond to methionine starvation like yeast starving for natural nutrients such as phosphate or sulfate: they undergo a uniform cell cycle arrest, conserve glucose, and survive. In contrast, methionine auxotrophs with defects in the transcription factors Met31p and Met32p respond poorly, like other auxotrophs. We combined physiological and gene expression data from a variety of nutrient starvations (in both respiratory competent and incompetent cells) to show that successful starvation response is correlated with expression of genes encoding oxidative stress response and nonrespiratory mitochondrial functions, but not respiration per se.U nderstanding global coordination of subcellular processes during adaptation to environmental change is a central challenge in systems biology. The ability of free-living organisms to adapt to changes in their nutritional environment is clearly one of the driving forces of their evolution. In natural environments, yeast are exposed to extreme variations in "natural nutrient" availability, particularly in their sources of carbon (and energy), phosphorus, sulfur, and nitrogen. Unlike wild type strains, auxotrophic mutant yeast strains unable to make an essential metabolite (e.g., leucine or uracil) can also be starved for the missing metabolite, but adaptation to this kind of "nonnatural" starvation has not been subject to evolutionary selection. Starvation of Saccharomyces cerevisiae for a single, growth-limiting nutrient offers the opportunity to study the coordination of nutrient sensing, metabolism, growth, and cell division. Proper coordination results in prolonged survival, concerted cell cycle arrest, and glucose conservation during starvation, and depends strongly on the specific nutrient being depleted. For instance, the survival of auxotrophic yeast starved for leucine, histidine, or uracil is substantially impaired (exhibiting a roughly 10-fold difference in half-life) relative to the same strain starved for the "natural" nutrients sulfate or phosphate (1). Starvation for sulfate or phosphate elicits rapid, nearly uniform G0/G1 cell cycle arrest and slows glucose consumption, whereas starvation for leucine, histidine, or uracil results in incomplete cell cycle arrest and markedly higher rates of glucose consumption.We are interested in understanding what, if any, general principles determine starvation phenotype. Early work on nutrient starvation posited the existence of a starvation "signal" that promotes concerted cell cycle arrest and surviv...

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mentioning

confidence: 76%

Survival of starving yeast is correlated with oxidative stress response and nonrespiratory mitochondrial function

Petti

Crutchfield

Rabinowitz

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

103

120

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“…Whereas binding of AICAR stimulates the formation of a Pho2p-Pho4p heterodimer, binding of AICAR and SAICAR directs Pho2p-Bas1p binding. These newly formed transcription factor complexes cooperatively induce the expression of genes involved in purine biosynthesis and phosphate utilization pathways [47]. The rationale for a differential response to changes in AICAR and SAICAR could be based on the dual function of these metabolites in inosine monophosphate (IMP) and AMP biosynthesis; the assembly of two competing transcription factor complexes could facilitate a differential response to changes in the de novo pathway and altered GMP:AMP ratios [47,48].…”

Section: Reviewmentioning

confidence: 99%

Regulatory crosstalk of the metabolic network

Grüning

Lehrach

Ralser

2010

Trends in Biochemical Sciences

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The metabolic network has a modular architecture, is robust to perturbations, and responds to biological stimuli and environmental conditions. Through monitoring by metabolite responsive macromolecules, metabolic pathways interact with the transcriptome and proteome. Whereas pathway interconnecting cofactors and substrates report on the overall state of the network, specialised intermediates measure the activity of individual functional units. Transitions in the network affect many of these regulatory metabolites, facilitating the parallel regulation of the timing and control of diverse biological processes. The metabolic network controls its own balance, chromatin structure and the biosynthesis of molecular cofactors; moreover, metabolic shifts are crucial in the response to oxidative stress and play a regulatory role in cancer.Evolution of the metabolic network and its structure Life probably began with the formation of compartmentalised autocatalytic chemical cycles. With the appearance of complex catalysts (ribonucleic acid-or protein-based enzymes), these cycles gained complexity, and evolved in their effectiveness and robustness [1]. These metabolic pathways now form the basis for life.As was the case for the first primitive life forms, the survival of today's complex organisms depends on the robustness and functionality of the metabolic framework [2]. To prevent and counteract perturbations in the flux, many biological control and sensor systems have evolved around the metabolic network. Metabolic pathways provide the cell with energy and supply macromolecular synthesis pathways with their required intermediates. They also balance metabolic systems under a variety of physiological conditions, and act as transducers and sensor systems for environmental conditions and stimuli. In addition, metabolic pathways are essential for crosstalk between metabolic regulatory components and the cellular transcriptome and proteome.As early as the 1960s, the principle that cells alter their gene expression in response to metabolic requirements has been known. The seminal work of Jacob and Monod, investigating the lac operon, uncovered one of the first examples of chemical-genetic regulation, by which bacterial cells adjust their enzyme production to the nutrient supply [3]. However, only recently have the broader implications of this principle emerged. Indeed, changes in the metabolic network not only control the metabolome, but they also have wide-ranging regulatory functions throughout biology.Most of the biochemical mechanisms that link the metabolic network to the transcriptome and proteome are incompletely understood. However, one type of regulation appears to be common: representative network intermediates bind to and modulate sensor function and activity of transcription factors, translational regulators, chromatin, enzymes, RNA molecules, and ion channels. Significant transcriptional changes around these intermediates identified them as reporter metabolites [4,5]. The use of intermediates as activity reporters ne...

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“…Promoter analysis was performed using the web-based software Regulatory Sequence Analysis (RSA) tools (van Helden et al, 1998). The statistical assessment of overrepresentation of GO biological processes categories (http://www.geneontology.org/) among sets of significantly changed transcripts was achieved as previously described in (Kresnowati et al, 2006). Heat-map visualizations of the average normalized transcript data were generated with Expressionist Analyst v 3.2 (Genedata, Basel, Switzerland).…”

Section: Data Acquisition and Analysismentioning

confidence: 99%

Heterologous carotenoid production in Saccharomyces cerevisiae induces the pleiotropic drug resistance stress response

Verwaal

Jiang

Wang

et al. 2010

Yeast

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To obtain insight into the genome-wide transcriptional response of heterologous carotenoid production in Saccharomyces cerevisiae, the transcriptome of two different S. cerevisiae strains overexpressing carotenogenic genes from the yeast Xanthophyllomyces dendrorhous grown in carbon-limited chemostat cultures was analysed. The strains exhibited different absolute carotenoid levels as well as different intermediate profiles. These discrepancies were further sustained by the difference of the transcriptional response exhibited by the two strains. Transcriptome analysis of the strain producing high carotenoid levels resulted in specific induction of genes involved in pleiotropic drug resistance (PDR). These genes encode ABC-type and major facilitator transporters which are reported to be involved in secretion of toxic compounds out of cells. β-Carotene was found to be secreted when sunflower oil was added to the medium of S. cerevisiae cells producing high levels of carotenoids, which was not observed when added to X. dendrorhous cells. Deletion of pdr10, one of the induced ABC transporters, decreased the transformation efficiency of a plasmid containing carotenogenic genes. The few transformants that were obtained had decreased growth rates and lower carotenoid production levels compared to a pdr5 deletion and a reference strain transformed with the same genes. Our results suggest that production of high amounts of carotenoids in S. cerevisiae leads to membrane stress, in which Pdr10 might play an important role, and a cellular response to secrete carotenoids out of the cell.

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When transcriptome meets metabolome: fast cellular responses of yeast to sudden relief of glucose limitation

Cited by 185 publications

References 74 publications

Survival of starving yeast is correlated with oxidative stress response and nonrespiratory mitochondrial function

Survival of starving yeast is correlated with oxidative stress response and nonrespiratory mitochondrial function

Regulatory crosstalk of the metabolic network

Heterologous carotenoid production in Saccharomyces cerevisiae induces the pleiotropic drug resistance stress response

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