File Name: a two way street reciprocal regulation of metabolism and signalling .zip
Protocol DOI: Metabolic alterations have been identified as a frequent event in cancer. This is often associated with increased flux through glycolysis, and also a secondary pathway to glycolysis, hexosamine biosynthetic pathway HBP.
Acetyl-CoA represents a key node in metabolism due to its intersection with many metabolic pathways and transformations. Emerging evidence reveals that cells monitor the levels of acetyl-CoA as a key indicator of their metabolic state, through distinctive protein acetylation modifications dependent on this metabolite. We offer the following conceptual model for understanding the role of this sentinel metabolite in metabolic regulation. Fluctuations in acetyl-CoA within these subcellular compartments enable the substrate-level regulation of acetylation modifications, but also necessitates the function of sirtuin deacetylases to catalyze removal of spontaneous modifications that might be unintended. Thus, understanding the sources, fates, and consequences of acetyl-CoA as a carrier of two-carbon units has started to reveal its underappreciated but profound influence on the regulation of numerous life processes. In response to a dynamic nutrient environment, cells must assess their metabolic state to decide whether to grow, survive, or die. It has become evident that metabolites themselves must feed back to regulate gene expression, signal transduction, and various protein activities in cellular decision-making processes [ 1 , 2 ].
We also describe how the metabolic adaptation of cancer cells influences this crosstalk to regulate protumorigenic signaling pathways. We suggest that the dual targeting of these processes might provide unprecedented opportunities for anticancer strategies. Cell proliferation requires increased biomass and energy supply, which is provided by metabolic adaptation. Despite the presence of adequate oxygen O 2 levels to support mitochondrial respiration, cancer cells are highly glycolytic and, as such, demonstrate increased glucose consumption and lactate production, a phenomenon known as the Warburg effect Vander Heiden et al. Interestingly, preclinical evidence for the therapeutic potential of combined strategies is emerging Park et al.
Research Article Oncology Free access Address correspondence to: Dario C. Phone: Find articles by Caino, M. Find articles by Chae, Y. Find articles by Vaira, V.
The classical functions of bone are the maintenance of phosphorus-calcium homeostasis, damage repair, as well its structural function which allows locomotion and protects the vital organs. The recent discovery of new functions for bone in the regulation of energy metabolism suggest that bone may be an endocrine organ. In the last decade, different genetic and molecular studies carried out in mice have determined that osteocalcin increases the secretion of insulin, and sensitivity to it, by increasing the secretion of adiponectin, stimulates the proliferation and the better functioning of the beta cells, promotes the reduction of fatty mass and an increase in the consumption of energy. These findings demonstrate the existence of a reciprocal regulation between bone and energy metabolism, mediated by osteocalcin. The recognition of the metabolic role of osteocalcin is a significant discovery in the field of osteology and endocrinology, bringing the possibility of new therapies in the treatment and prevention of metabolic diseases such as diabetes mellitus, sarcopenia, obesity and osteoporosis.
For almost all cells, nutrient availability, from glucose to amino acids, dictates their growth or developmental programs. This nutrient availability is closely coupled to the overall intracellular metabolic state of the cell. Therefore, cells have evolved diverse, robust and versatile modules to sense intracellular metabolic states, activate signaling outputs and regulate outcomes to these states. Yet, signaling and metabolism have been viewed as important but separate. This short review attempts to position aspects of intracellular signaling from a metabolic perspective, highlighting how conserved, core principles of metabolic sensing and signaling can emerge from an understanding of metabolic regulation.
Metabolic control of gene expression coordinates the levels of specific gene products to meet cellular demand for their activities. However, little is known about how metabolic signals affect the balance between enzymatic and regulatory roles of these dual functional proteins.
Since recently it has been found that SARS-coronavirus are dependent on the host transcriptional factors TF to express the viral genes, efforts are required to understand the molecular interplay between virus and host response. Read More. Electronic address:. Vascular smooth muscle cells are unusual in that differentiated, contractile cells possess the capacity to "de-differentiate" into a synthetic phenotype that is characterized by being replicative, secretory, and migratory. One aspect of this phenotypic modulation is a shift from voltage-gated Ca signalling in electrically coupled, differentiated cells to increased dependence on store-operated Ca entry and sarcoplasmic reticulum Ca release in synthetic cells.
Histone acetylation is sensitive to the availability of acetyl-CoA. However, the extent to which metabolic alterations in cancer cells impact tumor histone acetylation has been unclear. Here, we discuss our recent findings that oncogenic AKT1 activation regulates histone acetylation levels in tumors through regulation of acetyl-CoA metabolism.
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Signalling is known to regulate metabolism, and it is becoming clear that this regulation is reciprocal, with signalling pathways being regulated.Tentbarverbti 18.05.2021 at 02:28
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