metabolic signalling
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2021 ◽  
Vol 22 (23) ◽  
pp. 13166
Author(s):  
Salma Sultan ◽  
Walid Mottawea ◽  
JuDong Yeo ◽  
Riadh Hammami

Over the past decade, gut microbiota dysbiosis has been linked to many health disorders; however, the detailed mechanism of this correlation remains unclear. Gut microbiota can communicate with the host through immunological or metabolic signalling. Recently, microbiota-released extracellular vesicles (MEVs) have emerged as significant mediators in the intercellular signalling mechanism that could be an integral part of microbiota-host communications. MEVs are small membrane-bound vesicles that encase a broad spectrum of biologically active compounds (i.e., proteins, mRNA, miRNA, DNA, carbohydrates, and lipids), thus mediating the horizontal transfer of their cargo across intra- and intercellular space. In this study, we provide a comprehensive and in-depth discussion of the biogenesis of microbial-derived EVs, their classification and routes of production, as well as their role in inter-bacterial and inter-kingdom signaling.


2021 ◽  
Author(s):  
Xiang Li ◽  
Dongjing Deng ◽  
Gizem Cataltepe ◽  
Ángela Román ◽  
Carolina Cassano Monte Bello ◽  
...  

Sugars are essential metabolites for energy and anabolism that can also act as signals to regulate plant physiology and development. Experimental tools to disrupt major sugar signalling pathways are limited. We have performed a chemical screen for modifiers of activation of circadian gene expression by sugars to discover pharmacological tools to investigate and manipulate plant sugar signalling. Using a library of commercially available bioactive compounds, we identified 75 confident hits that modified the response of a circadian luciferase reporter to sucrose in dark-adapted seedlings. We validated the transcriptional effect on a subset of the hits and measured their effects on a range of sugar-dependent phenotypes for 13 of these chemicals. Chemicals were identified that appear to influence known and unknown sugar signalling pathways. Pentamidine isethionate (PI) was identified as a modifier of a sugar-activated Ca2+ signal that acts downstream of superoxide in a metabolic signalling pathway affecting circadian rhythms, primary metabolism and plant growth. Our data provide a resource of new experimental tools to manipulate plant sugar signalling and identify novel components of these pathways.


2021 ◽  
Author(s):  
Waeil Al Youssef ◽  
Regina Feil ◽  
Maureen Saint-Sorny ◽  
Xenie Johnson ◽  
John E. Lunn ◽  
...  

Singlet oxygen (1O2) induces retrograde signalling in chloroplasts. Using a novel mutant screen, we identified a mutation in the TREHALOSE-6-PHOSPHATE PHOSPHATASE 1 (T6PP1) gene that results in accumulation of trehalose 6-phosphate, a reprogramming of cell metabolism, and impairment of 1O2-induced retrograde signalling in Chlamydomonas reinhardtii. From transcriptomic analysis and metabolite profiling, we conclude that accumulation or deficiency of certain metabolites directly affect 1O2-signalling. 1O2-inducible GLUTATHIONE PEROXIDASE 5 (GPX5) gene expression is suppressed by increased content of fumarate, an intermediate in the tricarboxylic acid cycle (TCA cycle) in mitochondria and dicarboxylate metabolism in the cytosol, while it is promoted by another TCA cycle intermediate, aconitate. Furthermore, genes encoding known essential components of chloroplast-to-nucleus 1O2-signalling show decreased transcript levels in a t6pp1 mutant, which can be rescued by exogenous application of aconitate. We demonstrate that chloroplast retrograde signalling involving 1O2 depends on mitochondrial and cytosolic processes and that the metabolic status of the cell determines the response to 1O2.


2021 ◽  
Vol 13 (4) ◽  
pp. 555-568
Author(s):  
Emanuele Bartolini

Epileptic encephalopathies often have a genetic etiology. The epileptic activity itself exerts a direct detrimental effect on neurodevelopment, which may add to the cognitive impairment induced by the underlying mutation (“developmental and epileptic encephalopathy”). The focus of this review is on inherited syndromes. The phenotypes of genetic disorders affecting ion channels, metabolic signalling, membrane trafficking and exocytosis, cell adhesion, cell growth and proliferation are discussed. Red flags suggesting family of genes or even specific genes are highlighted. The knowledge of the phenotypical spectrum can indeed prompt the clinician to suspect specific etiologies, expediting the diagnosis.


Author(s):  
Nidhi Kedia-Mehta ◽  
Laura Tobin ◽  
Vanessa Zaiatz-Bittencourt ◽  
Marta Pisarska ◽  
Conor De Barra ◽  
...  

Natural killer (NK) cells are a population of innate immune cells which can rapidily kill cancer cells and produce cytokines such as interferon gamma (IFN-gamma). A key feature of NK cells is their ability to respond without prior sensitation, however it is now well established that NK cells can possess memory-like features. After activation with cytokines, NK cells demonstrate enhanced effector functions upon restimulation days or weeks later. This demonstrates that NK cells may be "trained" to be more effective killers and harnessed as more potent cancer immunotherapy agents. We have previously demonstrated that cellular metabolism is essential for NK cell responses, with NK cells upregulating both glycolysis and oxidative phosphorylation upon cytokine stimulation. Limiting NK cell metabolism results in reduced cytotoxicity and cytokine production. We have also demonstrated that defective NK cell responses in obesity are linked to defective cellular metabolism. In the current study we investigated if cellular metabolism is required during the initial period of NK cell cytokine training, and if NK cells from people with obesity (PWO) can be effectively trained. We show that increased flux through glycolysis and OXPHOS during the initial cytokine activation period is essential for NK cell training, as is the metabolic signalling factor Srepb. We show that NK cells from PWO, which are metabolically defective, display impaired NK cell training, which may have implications for immunotherapy in this particularly vulnerable group.


2021 ◽  
Vol 141 (10) ◽  
pp. S205
Author(s):  
K. Göbel ◽  
E. Wachsmuth ◽  
J. Stinn ◽  
X. Lim ◽  
M. van Steensel ◽  
...  

2021 ◽  
Vol 18 (2) ◽  
pp. 357-366
Author(s):  
Utpal Jagdish Dongre

Obesity is a chronic metabolic disease that affects both the pediatric and adult populations. Adipose tissue acts as an endocrine organ which secretes various adipokines involved in fat mass regulation and energy balance via modulating the metabolic signalling pathways. Altered secretion of adipokines promotes multiple complications, including insulin resistance. The primary mechanism of action that underlines the involvement of adipokines in the development of insulin resistance includes phosphorylation/de-phosphorylation of insulin receptor substrate-1 (IRS-1) facilitate by other signalling molecules like a suppressor of cytokine signalling 1 (SOCS-1). Adipokines mediated insulin resistance further contribute to the development of atherosclerosis, dyslipidemia, fatty liver disease, cancer etc. Thus, this review provides recent updates on the role of resistin, lipocalin-2, RBP-4, chemerin, TNF-alpha and IL-6 adipokines in the progression of insulin resistance.


2021 ◽  
Author(s):  
Esteban Salazar-Petres ◽  
Daniela Pereira Carvalho ◽  
Jorge Lopez-Tello ◽  
Amanda Sferruzzi-Perri

Fetal growth depends on placental function, which requires energy supplied by mitochondria. Here we investigated whether mitochondrial function in the placenta relates to growth of the lightest and heaviest fetuses of each sex within the litter of mice. Placentas from the lightest and heaviest fetuses were taken to evaluate placenta morphology (stereology), mitochondrial energetics (high-resolution respirometry), and mitochondrial regulators, nutrient transporters, hormone handling and signalling pathways (qPCR and western blotting). We found that mitochondrial complex I and II oxygen consumption rate was greater for placentas supporting the lightest female fetuses, although placental complex I abundance of the lightest females and complexes III and V of the lightest males were decreased compared to their heaviest counterparts. Expression of mitochondrial biogenesis (Nrf1) and fission (Drp1 and Fis1) genes was lower in the placenta from the lightest females, whilst biogenesis-related gene Tfam was greater in the placenta of the lightest male fetuses. Additionally, placental morphology and steroidogenic gene (Cyp17a1 and Cyp11a1) expression were aberrant for the lightest females, but glucose transporter (Glut1) expression lower in only the lightest males versus their heaviest counterparts. Differences in intra-litter placental phenotype were related to sex-dependent changes in the expression of hormone responsive (androgen receptor) and metabolic signalling pathways (AMPK, AKT, PPARγ). Thus, in normal mouse pregnancy, placental structure, function and mitochondrial phenotype are differentially responsive to growth of the female and the male fetus. This study may inform the design of sex-specific therapies for placental insufficiency and fetal growth abnormalities with life-long benefits for the offspring.


2021 ◽  
Author(s):  
Mehrshad Sadria ◽  
Anita Layton ◽  
Deokhwa Seo

Nutrient acquisition and metabolism pathways are altered in cancer cells to meet bioenergetic and biosynthetic demands. A major regulator of cellular metabolism and energy homeostasis, in normal and cancer cells, is AMP-activated protein kinase (AMPK). AMPK influences cell growth via its modulation of the mechanistic target of Rapamycin (mTOR) pathway, specifically, by inhibiting mTOR complex mTORC1, which facilitates cell proliferation, and by activating mTORC2 and cell survival. Given its conflicting roles, the effects of AMPK activation in cancer can be counter-intuitive. Prior to the establishment of cancer, AMPK acts as a tumor suppressor. However, following the onset of cancer, AMPK has been shown to either suppress or promote cancer, depending on cell type or state. To unravel the controversial roles of AMPK in cancer, we developed a computational model to simulate the effects of pharmacological maneuvers that target key metabolic signalling nodes, with specific focus on AMPK, mTORC, and their modulators. Model simulations clarify the competing effects and the roles of key metabolic signalling pathways in tumorigenesis, which may yield insights on innovative therapeutic strategies.


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