scholarly journals Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree Effect

Processes ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1496 ◽  
Author(s):  
Laetitia Gibart ◽  
Rajeev Khoodeeram ◽  
Gilles Bernot ◽  
Jean-Paul Comet ◽  
Jean-Yves Trosset
Keyword(s):  
Carbon Metabolism ◽  
Formal Model ◽  
Biological Properties ◽  
Central Carbon Metabolism ◽  
Metabolic Phenotype ◽  
Eukaryotic Cells ◽  
Crabtree Effect ◽  
Modeling Framework ◽  
Cell Microenvironment ◽  
Central Carbon

Adaptation of metabolism is a response of many eukaryotic cells to nutrient heterogeneity in the cell microenvironment. One of these adaptations is the shift from respiratory to fermentative metabolism, also called the Warburg/Crabtree effect. It is a response to a very high nutrient increase in the cell microenvironment, even in the presence of oxygen. Understanding whether this metabolic transition can result from basic regulation signals between components of the central carbon metabolism are the the core question of this work. We use an extension of the René Thomas modeling framework for representing the regulations between the main catabolic and anabolic pathways of eukaryotic cells, and formal methods for confronting models with known biological properties in different microenvironments. The formal model of the regulation of eukaryote metabolism defined and validated here reveals the conditions under which this metabolic phenotype switch occurs. It clearly proves that currently known regulating signals within the main components of central carbon metabolism can be sufficient to bring out the Warburg/Crabtree effect. Moreover, this model offers a general perspective of the regulation of the central carbon metabolism that can be used to study other biological questions.

scholarly journals Metformin Targets Central Carbon Metabolism and Reveals Mitochondrial Requirements in Human Cancers

2016 ◽  
Vol 24 (5) ◽  
pp. 728-739 ◽  
Author(s):  
Xiaojing Liu ◽  
Iris L. Romero ◽  
Lacey M. Litchfield ◽  
Ernst Lengyel ◽  
Jason W. Locasale
Keyword(s):  
Carbon Metabolism ◽  
Central Carbon Metabolism ◽  
Human Cancers ◽  
Central Carbon

Trisomy 21 results in modest impacts on mitochondrial function and central carbon metabolism

2021 ◽  
Author(s):  
Colin C. Anderson ◽  
John O. Marentette ◽  
Kendra M. Prutton ◽  
Abhishek K. Rauniyar ◽  
Julie A. Reisz ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Carbon Metabolism ◽  
Trisomy 21 ◽  
Central Carbon Metabolism ◽  
Central Carbon

Metabolic phenotyping of the Yersinia high-pathogenicity island that regulates central carbon metabolism

The Analyst ◽  
2015 ◽  
Vol 140 (10) ◽  
pp. 3356-3361 ◽  
Author(s):  
Leyu Yan ◽  
Wenna Nie ◽  
Haitao Lv
Keyword(s):  
Carbon Metabolism ◽  
Virulence Genes ◽  
Pathogenicity Island ◽  
Central Carbon Metabolism ◽  
Metabolic Phenotyping ◽  
High Pathogenicity ◽  
Central Carbon ◽  
Regulatory Effects

The regulatory effects of the HPI virulence genes on central carbon metabolism differentiate UPEC from non-UPEC.

scholarly journals HexR Controls Glucose-Responsive Genes and Central Carbon Metabolism in Neisseria meningitidis

2015 ◽  
Vol 198 (4) ◽  
pp. 644-654 ◽  
Author(s):  
Ana Antunes ◽  
Giacomo Golfieri ◽  
Francesca Ferlicca ◽  
Marzia M. Giuliani ◽  
Vincenzo Scarlato ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Neisseria Meningitidis ◽  
Microarray Analysis ◽  
Carbon Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Transcriptional Regulator ◽  
Central Carbon Metabolism ◽  
Binding Motif ◽  
Content Type ◽  
Central Carbon

ABSTRACTNeisseria meningitidis, an exclusively human pathogen and the leading cause of bacterial meningitis, must adapt to different host niches during human infection.N. meningitidiscan utilize a restricted range of carbon sources, including lactate, glucose, and pyruvate, whose concentrations vary in host niches. Microarray analysis ofN. meningitidisgrown in a chemically defined medium in the presence or absence of glucose allowed us to identify genes regulated by carbon source availability. Most such genes are implicated in energy metabolism and transport, and some are implicated in virulence. In particular, genes involved in glucose catabolism were upregulated, whereas genes involved in the tricarboxylic acid cycle were downregulated. Several genes encoding surface-exposed proteins, including the MafA adhesins andNeisseriasurface protein A, were upregulated in the presence of glucose. Our microarray analysis led to the identification of a glucose-responsivehexR-like transcriptional regulator that controls genes of the central carbon metabolism ofN. meningitidisin response to glucose. We characterized the HexR regulon and showed that thehexRgene is accountable for some of the glucose-responsive regulation;in vitroassays with the purified protein showed that HexR binds to the promoters of the central metabolic operons of the bacterium. Based on DNA sequence alignment of the target sites, we propose a 17-bp pseudopalindromic consensus HexR binding motif. Furthermore,N. meningitidisstrains lackinghexRexpression were deficient in establishing successful bacteremia in an infant rat model of infection, indicating the importance of this regulator for the survival of this pathogenin vivo.IMPORTANCENeisseria meningitidisgrows on a limited range of nutrients during infection. We analyzed the gene expression ofN. meningitidisin response to glucose, the main energy source available in human blood, and we found that glucose regulates many genes implicated in energy metabolism and nutrient transport, as well as some implicated in virulence. We identified and characterized a transcriptional regulator (HexR) that controls metabolic genes ofN. meningitidisin response to glucose. We generated a mutant lacking HexR and found that the mutant was impaired in causing systemic infection in animal models. SinceN. meningitidislacks known bacterial regulators of energy metabolism, our findings suggest that HexR plays a major role in its biology by regulating metabolism in response to environmental signals.

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