Where in the cell is SIRT3?--functional localization of an NAD+-dependent protein deacetylase

The ability to sense and respond to nutritional cues is among the most fundamental processes that support life in living organisms. At the cellular level, a number of biochemical mechanisms have been proposed to mediate cellular glucose sensing. These include ATP-sensitive potassium channels, AMP-activated protein kinase, activation of PKC (protein kinase C), and flux through the hexosamine pathway. Less well known is how cellularly heterogenous organs couple nutrient availability to prioritization of cell autonomous functions and appropriate growth of the entire organ. Yet what is clear is that when such mechanisms fail or become inappropriately active they can lead to dire consequences such as diabetes, metabolic syndromes, cardiovascular diseases and cancer. In this issue of the Biochemical Journal, Anagnostou and Shepherd report the identification of an important link between cellular glucose sensing and the Wnt/beta-catenin signalling pathway in macrophages. Their data strongly indicate that the Wnt/beta-catenin pathway of Wnt signalling is responsive to physiological concentrations of nutrients but also suggests that that this system could be inappropriately activated in the diabetic (hyperglycaemic) or other metabolically compromised pathological states. This opens the exciting possibility that organ-selective modulation of Wnt signalling may become an attractive therapeutic target to treat these diseases.     

Inositol and phosphatidylinositol mediated mediated glucose derepression, gene expression and invertase secretion in yeasts

Glucose Repression [1,2] Saccharomyces cerevisiae and other yeasts can growwell on different kinds of carbon sources. However,glucose and fructose are the best carbon sources for theirgrowth. When the medium contains glucose or fructose,the biosynthesis of enzyme catalyzing degradation of othercarbon sources will be greatly reduced or stopped. Thisphenomenon is called glucose repression. Although much progress has been made in this field,the exact mechanisms of glucose repression in yeastsa…     

Conservation of PHO pathway in ascomycetes and the role of Pho84

In budding yeast, Saccharomyces cerevisiae, the phosphate signalling and response pathway, known as PHO pathway, monitors phosphate cytoplasmic levels by controlling genes involved in scavenging, uptake and utilization of phosphate. Recent attempts to understand the phosphate starvation response in other ascomycetes have suggested the existence of both common and novel components of the budding yeast PHO pathway in these ascomycetes. In this review, we discuss the components of PHO pathway, their roles in maintaining phosphate homeostasis in yeast and their conservation across ascomycetes. The role of high-affinity transporter, Pho84, in sensing and signalling of phosphate has also been discussed     

Control of high osmolarity signalling in the yeast Saccharomyces cerevisiae

Signal transduction pathways control cellular responses to extrinsic and intrinsic signals. The yeast HOG (High Osmolarity Glycerol) response pathway mediates cellular adaptation to hyperosmotic stress. Pathway architecture as well as the flow of signal have been studied to a very high degree of detail. Recently, the yeast HOG pathway has become a popular model to analyse systems level properties of signal transduction. Those studies addressed, using experimentation and modelling, the role of basal signalling, robustness against perturbation, as well as adaptation and feedback control. These recent findings provide exciting insight into the higher control levels of signalling through this MAPK system of potential general importance.     

Why and How Do Plant Cells Sense Sugars?

The ability to sense sugars is crucial for the modulation ofgene expression in plants. Despite the importance of this phenomenon,our knowledge of sugar sensing in plants is scant. Several valuablehypotheses have been put forward based on the extensive knowledgeof sugar sensing in yeast. In recent years, tests of these hypotheseshave shown that hexokinase and sucrose-non-fermenting- (SNF-)related proteins appear to be involved in sugar sensing andtransduction, not only in yeast but also in higher plants. However,even if plants share with yeast some elements involved in sugarsensing, several aspects of sugar perception are likely to bepeculiar to higher plants. Plants should be able to sense notonly glucose but also other hexoses, such as fructose and disaccharides(sucrose, maltose and others). In this Botanical Briefing weoutline recent discoveries in this field, with emphasis on arabidopsisand cereals. The use of transgenic plants and mutants to identifysugar sensor(s) and elements in the signalling pathways andtheir cross-talk with the hormonal signalling is discussed.Copyright2001 Annals of Botany Company Abscisic acid, Arabidopsis thaliana, cereals, hexokinase, sugar sensing     

Less is more or more is less: Implications of glucose metabolism in the regulation of the reproductive potential and total lifespan of the Saccharomyces cerevisiae yeast

Carbohydrates are dietary nutrients that have an influence on cells physiology, cell reproductive capacity and, consequently, the lifespan of organisms. They are used in cellular processes after conversion to glucose, which is the primary source of energy and carbon skeleton for biosynthetic processes. Studies of the influence of glucose on cellular parameters and lifespan of organisms are primarily concerned with the effect of low glucose concentration defined as calorie restriction conditions. However, the effect of high glucose concentration on cell physiology is also very important. Thus, a comparative analysis of the effects of low and high glucose concentration conditions on cell efficiency was proposed with regard to reproductive capacity and total lifespan of the cell. Glucose concentration determines the type of metabolism and biosynthetic capabilities, which in turn, through the regulation on the cell size, may affect the reproductive capacity of cells. This study was conducted on yeast cells of wild-type and mutant strains Δgpa2 and Δgpr1 with glucose signalling pathway impairment. Such an experimental model enabled testing both the role of glucose concentration in the regulation of metabolic changes and the extent to which these changes depend on the extracellular or intracellular glucose concentrations. It has been shown here that calorie/glucose excess connected with changes in cell metabolic fluxes increases biosynthetic capabilities of yeast cells. This leads to an increase in cell dry weight accompanied by the increase in cell size and a simultaneous decrease in the reproductive potential and the overall length of cell life.     

Glucose-sensing mechanisms in eukaryotic cells

Glucose not only serves as a nutrient but also exerts many hormone-like regulatory effects in a wide variety of eukaryotic cell types. Recently, interest in identifying general mechanisms and principles used to sense the presence of glucose has significantly increased and promising advances have been made: in yeast, the first proteins with an apparently specific function in glucose detection have been discovered; in plant cells, there is increasing evidence for a diverse array of glucose-induced signalling mechanisms; and in mammals, glucose-sensing phenomena have turned out to be much more widespread than just in the well-known example of pancreatic beta cells.     

Feasting, fasting and fermenting. Glucose sensing in yeast and other cells

Glucose is the primary fuel for most cells. Because the amount of available glucose can fluctuate wildly, organisms must sense the amount available to them and respond appropriately. Altering gene expression is one of the major effects glucose has on cells. Two different glucose sensing and signal transduction pathways in the yeast S. cerevisiae--one for repression, and one for induction of gene expression--have recently come into focus. What we have learned about these glucose sensing and signaling mechanisms might shed light on how other cells sense and respond to glucose.     

Glucose-dependent and -independent signalling functions of the yeast glucose sensor Snf3

The yeast Snf3 protein has been described to function as a sensor for low concentrations of extracellular glucose. We have found that Snf3 is able to transduce a signal in the complete absence of extracellular glucose. High basal activity of the HXT7 promoter during growth on ethanol required Snf3 as well as other components of the signalling pathway activated by Snf3. Moreover, the C-terminal domain of Snf3 was sufficient to complement the role of Snf3 in this regulation. As the C-terminal tail of Snf3 interacted with other components at the plasma membrane independent of the carbon source, our data suggest that Snf3 is involved in signalling complexes which can be activated by other signals than extracellular glucose.     

DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme?

The DNA damage signalling pathway is a core element of the cellular response to genotoxic insult, and its components play key roles in defending against neoplastic transformation. Recent work has indicated that the human ATM and ATR proteins, and their yeast homologues, are intimately involved in sensing DNA damage, suggesting parallels with the DNA double-strand break repair enzyme DNA-PK.     

Novel mechanisms in nutrient activation of the yeast protein kinase A pathway

In yeast the Protein Kinase A (PKA) pathway can be activated by a variety of nutrients. Fermentable sugars, like glucose and sucrose, trigger a spike in the cAMP level, followed by activation of PKA and phosphorylation of target proteins causing a.o. mobilization of reserve carbohydrates, repression of stress-related genes and induction of growth-related genes. Glucose and sucrose are sensed by a G-protein coupled receptor system that activates adenylate cyclase and also activates a bypass pathway causing direct activation of PKA. Addition of other essential nutrients, like nitrogen sources or phosphate, to glucose-repressed nitrogen- or phosphate-starved cells, also triggers rapid activation of the PKA pathway. In these cases cAMP is not involved as a second messenger. Amino acids are sensed by the Gap1 transceptor, previously considered only as an amino acid transporter. Recent results indicate that the amino acid ligand has to induce a specific conformational change for signaling. The same amino acid binding site is involved in transport and signaling. Similar results have been obtained for Pho84 which acts as a transceptor for phosphate activation of the PKA pathway. Ammonium activation of the PKA pathway in nitrogen-starved cells is mediated mainly by the Mep2 transceptor, which belongs to a different class of transporter proteins. Hence, different types of sensing systems are involved in control of the yeast PKA pathway by nutrients.     

Novel insights into the osmotic stress response of yeast

Response to hyperosmolarity in the baker's yeast Saccharomyces cerevisiae has attracted a great deal of attention of molecular and cellular biologists in recent years, from both the fundamental scientific and applied viewpoint. Indeed the underlying molecular mechanisms form a clear demonstration of the intricate interplay of (environmental) signalling events, regulation of gene expression and control of metabolism that is pivotal to any living cell. In this article we briefly review the cellular response to conditions of hyperosmolarity, with focus on the high-osmolarity glycerol mitogen-activated protein kinase pathway as the major signalling route governing cellular adaptations. Special attention will be paid to the recent finding that in the yeast cell also major structural changes occur in order to ensure maintenance of cell integrity. The intriguing role of glycerol in growth of yeast under (osmotic) stress conditions is highlighted.