scholarly journals Selection for rapid uptake of scarce or fluctuating resource explains vulnerability of glycolysis to imbalance

2021 ◽  
Vol 17 (1) ◽  
pp. e1008547
Author(s):  
Albertas Janulevicius ◽  
G. Sander van Doorn
Keyword(s):  
Phosphate Transport ◽  
Sudden Increase ◽  
Cellular Functions ◽  
Glycolytic Intermediate ◽  
Maximum Reaction Rate ◽  
Reaction Rate Constants ◽  
Fitness Advantage ◽  
Atp Concentration ◽  
Glycolysis Pathway ◽  
Balanced Dynamics

Glycolysis is a conserved central pathway in energy metabolism that converts glucose to pyruvate with net production of two ATP molecules. Because ATP is produced only in the lower part of glycolysis (LG), preceded by an initial investment of ATP in the upper glycolysis (UG), achieving robust start-up of the pathway upon activation presents a challenge: a sudden increase in glucose concentration can throw a cell into a self-sustaining imbalanced state in which UG outpaces LG, glycolytic intermediates accumulate and the cell is unable to maintain high ATP concentration needed to support cellular functions. Such metabolic imbalance can result in “substrate-accelerated death”, a phenomenon observed in prokaryotes and eukaryotes when cells are exposed to an excess of substrate that previously limited growth. Here, we address why evolution has apparently not eliminated such a costly vulnerability and propose that it is a manifestation of an evolutionary trade-off, whereby the glycolysis pathway is adapted to quickly secure scarce or fluctuating resource at the expense of vulnerability in an environment with ample resource. To corroborate this idea, we perform individual-based eco-evolutionary simulations of a simplified yeast glycolysis pathway consisting of UG, LG, phosphate transport between a vacuole and a cytosol, and a general ATP demand reaction. The pathway is evolved in constant or fluctuating resource environments by allowing mutations that affect the (maximum) reaction rate constants, reflecting changing expression levels of different glycolytic enzymes. We demonstrate that under limited constant resource, populations evolve to a genotype that exhibits balanced dynamics in the environment it evolved in, but strongly imbalanced dynamics under ample resource conditions. Furthermore, when resource availability is fluctuating, imbalanced dynamics confers a fitness advantage over balanced dynamics: when glucose is abundant, imbalanced pathways can quickly accumulate the glycolytic intermediate FBP as intracellular storage that is used during periods of starvation to maintain high ATP concentration needed for growth. Our model further predicts that in fluctuating environments, competition for glucose can result in stable coexistence of balanced and imbalanced cells, as well as repeated cycles of population crashes and recoveries that depend on such polymorphism. Overall, we demonstrate the importance of ecological and evolutionary arguments for understanding seemingly maladaptive aspects of cellular metabolism.

scholarly journals Selection for rapid uptake of scarce or fluctuating resource explains vulnerability of glycolysis to imbalance

2019 ◽  
Author(s):  
Albertas Janulevicius ◽  
G. Sander van Doorn
Keyword(s):  
Resource Competition ◽  
Phosphate Transport ◽  
Sudden Increase ◽  
Glycolytic Intermediate ◽  
Maximum Reaction Rate ◽  
Reaction Rate Constants ◽  
Fitness Advantage ◽  
Atp Concentration ◽  
Glycolysis Pathway ◽  
Balanced Dynamics

AbstractGlycolysis is a conserved central pathway in energy metabolism that converts glucose to pyruvate with net production of two ATP molecules. Because ATP is produced only in the lower part of glycolysis (LG), preceded by an initial investment of ATP in the upper glycolysis (UG), achieving robust start-up of the pathway upon activation presents a challenge: a sudden increase in glucose concentration can throw a cell into a self-sustaining imbalanced state in which UG outpaces LG, glycolytic intermediates accumulate and the cell is unable to maintain high ATP concentration needed to support cellular functions. Such metabolic imbalance can result in “substrate-accelerated death”, a phenomenon observed in prokaryotes and eukaryotes when cells are exposed to an excess of substrate that previously limited growth. Here, we address why evolution has apparently not eliminated such a costly vulnerability and propose that it is a manifestation of an evolutionary trade-off, whereby the glycolysis pathway is adapted to quickly secure scarce or fluctuating resource at the expense of vulnerability in an environment with ample resource. To corroborate this idea, we perform evolutionary simulations of a simplified yeast glycolysis pathway consisting of UG, LG, phosphate transport between a vacuole and a cytosol, and a general ATP demand reaction. The pathway is evolved in constant or fluctuating resource environments by allowing mutations that affect the (maximum) reaction rate constants, reflecting changing expression levels of different glycolytic enzymes. We demonstrate that under limited constant resource, the population evolves to a genotype that is balanced but exhibits strongly imbalanced dynamics under ample resource conditions. Furthermore, when resource availability is fluctuating, the imbalanced phenotype enjoys a fitness advantage over balanced dynamics: when glucose is abundant, imbalanced pathways can quickly accumulate glycolytic intermediate FBP as intracellular storage that is used during periods of starvation to maintain high ATP concentration needed for growth. Our model further predicts that in environments with fluctuating resource, competition for glucose can result in stable coexistence of balanced and imbalanced cells, as well as repeated cycles of population crashes and recoveries that depend on such polymorphism. Overall, we demonstrate the importance of ecological and evolutionary arguments for understanding seemingly maladaptive aspects of cellular metabolism.

scholarly journals A single Na+-Pi cotransporter in Toxoplasma plays key roles in phosphate import and control of parasite osmoregulation

2020 ◽  
Vol 16 (12) ◽  
pp. e1009067
Author(s):  
Beejan Asady ◽  
Claudia F. Dick ◽  
Karen Ehrenman ◽  
Tejram Sahu ◽  
Julia D. Romano ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Critical Role ◽  
Inorganic Ions ◽  
Phosphate Transport ◽  
Cellular Functions ◽  
Growth Defects ◽  
Binding Domains ◽  
Cytoplasmic Vesicles ◽  
Survival Mode ◽  
And Control

Inorganic ions such as phosphate, are essential nutrients required for a broad spectrum of cellular functions and regulation. During infection, pathogens must obtain inorganic phosphate (Pi) from the host. Despite the essentiality of phosphate for all forms of life, how the intracellular parasite Toxoplasma gondii acquires Pi from the host cell is still unknown. In this study, we demonstrated that Toxoplasma actively internalizes exogenous Pi by exploiting a gradient of Na+ ions to drive Pi uptake across the plasma membrane. The Na+-dependent phosphate transport mechanism is electrogenic and functionally coupled to a cipargarmin sensitive Na+-H+-ATPase. Toxoplasma expresses one transmembrane Pi transporter harboring PHO4 binding domains that typify the PiT Family. This transporter named TgPiT, localizes to the plasma membrane, the inward buds of the endosomal organelles termed VAC, and many cytoplasmic vesicles. Upon Pi limitation in the medium, TgPiT is more abundant at the plasma membrane. We genetically ablated the PiT gene, and ΔTgPiT parasites are impaired in importing Pi and synthesizing polyphosphates. Interestingly, ΔTgPiT parasites accumulate 4-times more acidocalcisomes, storage organelles for phosphate molecules, as compared to parental parasites. In addition, these mutants have a reduced cell volume, enlarged VAC organelles, defects in calcium storage and a slightly alkaline pH. Overall, these mutants exhibit severe growth defects and have reduced acute virulence in mice. In survival mode, ΔTgPiT parasites upregulate several genes, including those encoding enzymes that cleave or transfer phosphate groups from phosphometabolites, transporters and ions exchangers localized to VAC or acidocalcisomes. Taken together, these findings point to a critical role of TgPiT for Pi supply for Toxoplasma and also for protection against osmotic stresses.

scholarly journals Growth-rate dependent resource investment in bacterial motile behavior quantitatively follows potential benefit of chemotaxis

2019 ◽  
Vol 117 (1) ◽  
pp. 595-601 ◽  
Author(s):  
Bin Ni ◽  
Remy Colin ◽  
Hannes Link ◽  
Robert G. Endres ◽  
Victor Sourjik
Keyword(s):  
Growth Rate ◽  
Carbon Sources ◽  
Relative Fitness ◽  
Cellular Functions ◽  
Bacterial Growth Rate ◽  
General Role ◽  
Resource Investment ◽  
Fitness Advantage ◽  
Rate Dependent ◽  
Nutrient Gradients

Microorganisms possess diverse mechanisms to regulate investment into individual cellular processes according to their environment. How these regulatory strategies reflect the inherent trade-off between the benefit and cost of resource investment remains largely unknown, particularly for many cellular functions that are not immediately related to growth. Here, we investigate regulation of motility and chemotaxis, one of the most complex and costly bacterial behaviors, as a function of bacterial growth rate. We show with experiment and theory that in poor nutritional conditions,Escherichia coliincreases its investment in motility in proportion to the reproductive fitness advantage provided by the ability to follow nutrient gradients. Since this growth-rate dependent regulation of motility genes occurs even when nutrient gradients are absent, we hypothesize that it reflects an anticipatory preallocation of cellular resources. Notably, relative fitness benefit of chemotaxis could be observed not only in the presence of imposed gradients of secondary nutrients but also in initially homogeneous bacterial cultures, suggesting that bacteria can generate local gradients of carbon sources and excreted metabolites, and subsequently use chemotaxis to enhance the utilization of these compounds. This interplay between metabolite excretion and their chemotaxis-dependent reutilization is likely to play an important general role in microbial communities.

scholarly journals The P. aeruginosa Type VI Secretion System Effector Tse5 Forms Ion-Selective Membrane Pores that Disrupt the Membrane Potential of Intoxicated Cells

2021 ◽  
Author(s):  
Amaia González-Magaña ◽  
Jon Altuna ◽  
María Queralt-Martín ◽  
Eneko Largo ◽  
Itxaso Montánchez ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Secretion System ◽  
Effector Proteins ◽  
Host Cells ◽  
Type Vi Secretion System ◽  
Cellular Functions ◽  
Fitness Advantage ◽  
Type Vi Secretion ◽  
Wide Range ◽  
Membrane Depolarisation

Abstract The Type VI Secretion System (T6SS) of Pseudomonas aeruginosa injects effector proteins into neighbouring competitors and host cells, providing a fitness advantage that allows this opportunistic nosocomial pathogen to persist and prevail during the onset of infections. However, despite the high clinical relevance of P. aeruginosa, the identity and mode of action of most P. aeruginosa T6SS-dependent effectors remain to be discovered. Here, we report the molecular mechanism of Tse5-CT, which is the toxic auto-proteolytic product of the P. aeruginosa T6SS exported effector Tse5. Our results demonstrate Tse5-CT is a pore-forming toxin that can transport ions across the membrane, causing membrane depolarisation and bacterial death. The membrane potential regulates a wide range of essential cellular functions, and therefore membrane depolarisation is an efficient strategy to compete with other microorganisms in polymicrobial environments.

Surface Structure of Nucleated Animal Cells: Carbon Replicas

1967 ◽  
Vol 25 ◽  
pp. 120-121
Author(s):  
Robert M. Glaeser ◽  
Thea B. Scott
Keyword(s):  
Cell Surface ◽  
Surface Structure ◽  
Particle Diameter ◽  
Cellular Functions ◽  
Animal Cells ◽  
Replica Technique ◽  
Carbon Replica ◽  
Characteristic Particle ◽  
Cell Surface Structure ◽  
Carbon Replicas

The carbon-replica technique can be used to obtain information about cell-surface structure that cannot ordinarily be obtained by thin-section techniques. Mammalian erythrocytes have been studied by the replica technique and they appear to be characterized by a pebbly or “plaqued“ surface texture. The characteristic “particle” diameter is about 200 Å to 400 Å. We have now extended our observations on cell-surface structure to chicken and frog erythrocytes, which possess a broad range of cellular functions, and to normal rat lymphocytes and mouse ascites tumor cells, which are capable of cell division. In these experiments fresh cells were washed in Eagle's Minimum Essential Medium Salt Solution (for suspension cultures) and one volume of a 10% cell suspension was added to one volume of 2% OsO4 or 5% gluteraldehyde in 0.067 M phosphate buffer, pH 7.3. Carbon replicas were obtained by a technique similar to that employed by Glaeser et al. Figure 1 shows an electron micrograph of a carbon replica made from a chicken erythrocyte, and Figure 2 shows an enlarged portion of the same cell.

Multimode light microscopy and fluorescence-based reagents as tools for the study of chemical and molecular dynamics of living cells and tissues

1992 ◽  
Vol 50 (1) ◽  
pp. 418-419
Author(s):  
D. L. Taylor
Keyword(s):  
Living Cells ◽  
Cellular Level ◽  
Molecular Techniques ◽  
Cellular Functions ◽  
Macromolecular Assemblies ◽  
Cell Functions ◽  
Molecular Events ◽  
Yield Information ◽  
Full Knowledge ◽  
Structural Methods

Cells function through the complex temporal and spatial interplay of ions, metabolites, macromolecules and macromolecular assemblies. Biochemical approaches allow the investigator to define the components and the solution chemical reactions that might be involved in cellular functions. Static structural methods can yield information concerning the 2- and 3-D organization of known and unknown cellular constituents. Genetic and molecular techniques are powerful approaches that can alter specific functions through the manipulation of gene products and thus identify necessary components and sequences of molecular events. However, full knowledge of the mechanism of particular cell functions will require direct measurement of the interplay of cellular constituents. Therefore, there has been a need to develop methods that can yield chemical and molecular information in time and space in living cells, while allowing the integration of information from biochemical, molecular and genetic approaches at the cellular level.

Correlation Between Cellular Functions and Morphological Changes of Human Trophoblast in Vitro

1975 ◽  
Vol 33 ◽  
pp. 600-601
Author(s):  
John C. Garancis ◽  
Robert O. Hussa ◽  
Michael T. Story ◽  
Donald Yorde ◽  
Roland A. Pattillo
Keyword(s):  
Electron Microscopy ◽  
Cellular Proliferation ◽  
Morphological Changes ◽  
Culture Fluid ◽  
Cellular Functions ◽  
Human Trophoblast ◽  
Transmission Electron ◽  
Marked Activity ◽  
Malignant Trophoblast

Human malignant trophoblast cells in continuous culture were incubated for 3 days in medium containing 1 mM N6-O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) and 1 mM theophylline. The culture fluid was replenished daily. Stimulated cultures secreted many times more chorionic gonadotropin and estrogens than did control cultures in the absence of increased cellular proliferation. Scanning electron microscopy revealed remarkable surface changes of stimulated cells. Control cells (not stimulated) were smooth or provided with varying numbers of microvilli (Fig. 1). The latter, usually, were short and thin. The surface features of stimulated cells were considerably different. There was marked increase of microvilli which appeared elongated and thick. Many cells were covered with confluent polypoid projections (Fig. 2). Transmission electron microscopy demonstrated marked activity of cytoplasmic organelles. Mitochondria were increased in number and size; some giant forms with numerous cristae were observed.

Signal-regulated oxidation of proteins via MICAL

2020 ◽  
Vol 48 (2) ◽  
pp. 613-620
Author(s):  
Clara Ortegón Salas ◽  
Katharina Schneider ◽  
Christopher Horst Lillig ◽  
Manuela Gellert
Keyword(s):  
Signal Transduction ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Redox Regulation ◽  
Signal Transduction Pathways ◽  
Cellular Functions ◽  
Intracellular Signals ◽  
Amino Acid Side Chains ◽  
Specific Receptors ◽  
Sulfur Containing

Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modifications of cysteinyl and methionyl residues have been characterised in countless signal transduction pathways. Due to the low reactivity of most sulfur-containing amino acid side chains with hydrogen peroxide, for instance, and also to ensure specificity, redox signalling requires catalysis, just like phosphorylation signalling requires kinases and phosphatases. While reducing enzymes of both cysteinyl- and methionyl-derivates have been characterised in great detail before, the discovery and characterisation of MICAL proteins evinced the first examples of specific oxidases in signal transduction. This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions.

Receptor Mediated Binding of the Fibrinolytic Components, Plasminogen and Urokinase, to Peripheral Blood Cells

1987 ◽  
Vol 58 (03) ◽  
pp. 936-942 ◽  
Author(s):  
Lindsey A Miles ◽  
Edward F Plow
Keyword(s):  
T Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Binding Sites ◽  
Blood Cells ◽  
High Capacity ◽  
Red Cells ◽  
Peripheral Blood Cells ◽  
Cellular Functions ◽  
Fibrinolytic Proteins

SummaryGlu-plasminogen binds to platelets; the monocytoid line, U937, and the human fetal fibroblast line, GM1380 bind both plasminogen and its activator, urokinase. This study assesses the interaction of these fibrinolytic proteins with circulating human blood cells. Plasminogen bound minimally to red cells but bound saturably and reversibly to monocytes, granulocytes and lymphocytes with apparent Kd values of 0.9-1.4 μM. The interactions were of high capacity with 1.6 to 49 × 105 sites/cell and involved the lysine binding sites of plasminogen. Both T cells and non-rosetting lymphocytes and two B cell lines saturably bound plasminogen. Urokinase bound saturably to gianulocytes, monocytes, non-rosetting lymphocytes and a B cell line, but minimally to T cells, platelets and red cells. Therefore, plasminogen binding sites of high capacity, of similar affinities, and with common recognition specificities are expressed by many peripheral blood cells. Urokinase receptors are also widely distributed, but less so than plasminogen binding sites. The binding ol plasminogen and/ or urokinase to these cells may lead to generation of cell- associated proteolytic activity which contributes to a variety of cellular functions.

TSH receptor-dependent cellular functions measured with the thyroid cell strain FRTL-5

1989 ◽  
Vol 120 (3_Suppl) ◽  
pp. S194
Author(s):  
B. E. WENZEL ◽  
A. HEUFELDER ◽  
T. MACKENROTH ◽  
P. C. SCRIBA
Keyword(s):  
Cell Strain ◽  
Tsh Receptor ◽  
Thyroid Cell ◽  
Cellular Functions
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