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FEMS Yeast Research Sep 2015Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of... (Review)
Review
Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration and gluconeogenesis. This dominant effect of glucose on yeast carbon metabolism is coordinated by several signaling and metabolic interactions that mainly regulate transcriptional activity but are also effective at post-transcriptional and post-translational levels. This review describes effects of glucose repression on yeast carbon metabolism with a focus on roles of the Snf3/Rgt2 glucose-sensing pathway and Snf1 signal transduction in establishment and relief of glucose repression.
Topics: Carbon; Catabolite Repression; Energy Metabolism; Gene Expression Regulation, Fungal; Glucose; Monosaccharide Transport Proteins; Protein Serine-Threonine Kinases; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 26205245
DOI: 10.1093/femsyr/fov068 -
Antioxidants & Redox Signaling Nov 2016Monocyte and macrophage dysfunction plays a critical role in a wide range of inflammatory disease processes, including obesity, impaired wound healing diabetic... (Review)
Review
SIGNIFICANCE
Monocyte and macrophage dysfunction plays a critical role in a wide range of inflammatory disease processes, including obesity, impaired wound healing diabetic complications, and atherosclerosis. Emerging evidence suggests that the earliest events in monocyte or macrophage dysregulation include elevated reactive oxygen species production, thiol modifications, and disruption of redox-sensitive signaling pathways. This review focuses on the current state of research in thiol redox signaling in monocytes and macrophages, including (i) the molecular mechanisms by which reversible protein-S-glutathionylation occurs, (ii) the identification of bona fide S-glutathionylated proteins that occur under physiological conditions, and (iii) how disruptions of thiol redox signaling affect monocyte and macrophage functions and contribute to atherosclerosis. Recent Advances: Recent advances in redox biochemistry and biology as well as redox proteomic techniques have led to the identification of many new thiol redox-regulated proteins and pathways. In addition, major advances have been made in expanding the list of S-glutathionylated proteins and assessing the role that protein-S-glutathionylation and S-glutathionylation-regulating enzymes play in monocyte and macrophage functions, including monocyte transmigration, macrophage polarization, foam cell formation, and macrophage cell death.
CRITICAL ISSUES
Protein-S-glutathionylation/deglutathionylation in monocytes and macrophages has emerged as a new and important signaling paradigm, which provides a molecular basis for the well-established relationship between metabolic disorders, oxidative stress, and cardiovascular diseases.
FUTURE DIRECTIONS
The identification of specific S-glutathionylated proteins as well as the mechanisms that control this post-translational protein modification in monocytes and macrophages will facilitate the development of new preventive and therapeutic strategies to combat atherosclerosis and other metabolic diseases. Antioxid. Redox Signal. 25, 816-835.
Topics: Animals; Atherosclerosis; Glutathione; Humans; Macrophages; Mitochondria; Monocytes; Oxidation-Reduction; Oxidative Stress; Protein Processing, Post-Translational; Proteins; Reactive Oxygen Species; Signal Transduction; Sulfhydryl Compounds
PubMed: 27288099
DOI: 10.1089/ars.2016.6697 -
Journal of Proteome Research Jan 2021Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization,... (Review)
Review
Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization, activity, stability, and complex formation. The deregulation of protein -acylation contributes to many diseases such as cancer and neurodegenerative disorders. The past decade has witnessed substantial progress in proteomic analysis of protein -acylation, which significantly advanced our understanding of -acylation biology. In this review, we summarized the techniques for the enrichment of -acylated proteins or peptides, critically reviewed proteomic studies of protein -acylation at eight different levels, and proposed major challenges for the -acylproteomics field. In summary, proteome-scale analysis of protein -acylation comes of age and will play increasingly important roles in discovering new disease mechanisms, biomarkers, and therapeutic targets.
Topics: Acylation; Lipoylation; Protein S; Proteome; Proteomics
PubMed: 33253586
DOI: 10.1021/acs.jproteome.0c00409 -
The New Phytologist Feb 2022Oomycete phytopathogens have adapted to colonise plants using effectors as their molecular weapons. Intracellular effectors, mostly proteins but also small ribonucleic... (Review)
Review
Oomycete phytopathogens have adapted to colonise plants using effectors as their molecular weapons. Intracellular effectors, mostly proteins but also small ribonucleic acids, are delivered by the pathogens into the host cell cytoplasm where they interfere with normal plant physiology. The diverse host processes emerging as 'victims' of these 'specialised bullets' include gene transcription and RNA-mediated silencing, cell death, protein stability, protein secretion and autophagy. Some effector targets are directly involved in defence execution, while others participate in fundamental metabolisms whose alteration collaterally affects defences. Other effector targets are susceptibility factors (SFs), that is host components that make plants vulnerable to pathogens. SFs are mostly negative regulators of immunity, but some seem necessary to sustain or promote pathogen colonisation.
Topics: Host-Pathogen Interactions; Oomycetes; Plant Diseases; Plant Immunity; Plants; Protein Transport; Proteins
PubMed: 34705271
DOI: 10.1111/nph.17828 -
International Journal of Molecular... Jul 2013Atherosclerosis is a chronic inflammatory disease involving the accumulation of monocytes and macrophages in the vascular wall. Monocytes and macrophages play a central... (Review)
Review
Atherosclerosis is a chronic inflammatory disease involving the accumulation of monocytes and macrophages in the vascular wall. Monocytes and macrophages play a central role in the initiation and progression of atherosclerotic lesion development. Oxidative stress, which occurs when reactive oxygen species (ROS) overwhelm cellular antioxidant systems, contributes to the pathophysiology of many chronic inflammatory diseases, including atherosclerosis. Major targets of ROS are reactive thiols on cysteine residues in proteins, which when oxidized can alter cellular processes, including signaling pathways, metabolic pathways, transcription, and translation. Protein-S-glutathionylation is the process of mixed disulfide formation between glutathione (GSH) and protein thiols. Until recently, protein-S-glutathionylation was associated with increased cellular oxidative stress, but S-glutathionylation of key protein targets has now emerged as a physiologically important redox signaling mechanism, which when dysregulated contributes to a variety of disease processes. In this review, we will explore the role of thiol oxidative stress and protein-S-glutathionylation in monocyte and macrophage dysfunction as a mechanistic link between oxidative stress associated with metabolic disorders and chronic inflammatory diseases, including atherosclerosis.
Topics: Animals; Atherosclerosis; Glutathione; Humans; Macrophages; Mice; Monocytes; NADPH Oxidases; Oxidation-Reduction; Oxidative Stress; Proteins; Rats; Reactive Oxygen Species; Sulfhydryl Compounds
PubMed: 23887649
DOI: 10.3390/ijms140815212 -
Traffic (Copenhagen, Denmark) Nov 2017Protein S-acylation, also known as palmitoylation, consists of the addition of a lipid molecule to one or more cysteine residues through a thioester bond. This... (Review)
Review
Protein S-acylation, also known as palmitoylation, consists of the addition of a lipid molecule to one or more cysteine residues through a thioester bond. This modification, which is widespread in eukaryotes, is thought to affect over 12% of the human proteome. S-acylation allows the reversible association of peripheral proteins with membranes or, in the case of integral membrane proteins, modulates their behavior within the plane of the membrane. This review focuses on the consequences of protein S-acylation on intracellular trafficking and membrane association. We summarize relevant information that illustrates how lipid modification of proteins plays an important role in dictating precise intracellular movements within cells by regulating membrane-cytosol exchange, through membrane microdomain segregation, or by modifying the flux of the proteins by means of vesicular or diffusional transport systems. Finally, we highlight some of the key open questions and major challenges in the field.
Topics: Acylation; Cysteine; Humans; Lipid Metabolism; Lipoylation; Membrane Microdomains; Membrane Proteins; Palmitates; Protein Transport
PubMed: 28837239
DOI: 10.1111/tra.12510 -
EMBO Reports Jul 2021In eukaryotic cells, DNA is tightly packed with the help of histone proteins into chromatin. Chromatin architecture can be modified by various post-translational... (Review)
Review
In eukaryotic cells, DNA is tightly packed with the help of histone proteins into chromatin. Chromatin architecture can be modified by various post-translational modifications of histone proteins. For almost 60 years now, studies on histone lysine acetylation have unraveled the contribution of this acylation to an open chromatin state with increased DNA accessibility, permissive for gene expression. Additional complexity emerged from the discovery of other types of histone lysine acylations. The acyl group donors are products of cellular metabolism, and distinct histone acylations can link the metabolic state of a cell with chromatin architecture and contribute to cellular adaptation through changes in gene expression. Currently, various technical challenges limit our full understanding of the actual impact of most histone acylations on chromatin dynamics and of their biological relevance. In this review, we summarize the state of the art and provide an overview of approaches to overcome these challenges. We further discuss the concept of subnuclear metabolic niches that could regulate local CoA availability and thus couple cellular metabolisms with the epigenome.
Topics: Acetylation; Acylation; Chromatin; Histones; Protein Processing, Post-Translational
PubMed: 34159701
DOI: 10.15252/embr.202152774 -
Applied and Environmental Microbiology Apr 2019Thioredoxins are small proteins that regulate the cellular redox state, prevent oxidative damage, and play an active role in cell repair. Oxidative stress has proven to...
Thioredoxins are small proteins that regulate the cellular redox state, prevent oxidative damage, and play an active role in cell repair. Oxidative stress has proven to be of much relevance in biotechnological processes when the metabolism of is mainly respiratory. During wine yeast starter production, active dry yeast cytosolic thioredoxin Trx2p is a key player in protecting metabolic enzymes from being oxidized by carbonylation. Less is known about the role of redox control during grape juice fermentation. A mutant strain that lacked both cytosolic thioredoxins, Trx1p and Trx2p, was tested for grape juice fermentation. Its growth and sugar consumption were greatly impaired, which indicates the system's relevance under fermentative conditions. A proteomic analysis indicated that deletion of the genes and caused a reduction in the ribosomal proteins and factors involved in translation elongation in addition to enzymes for glycolysis and amino acid biosynthesis. A metabolomic analysis of the Δ Δ mutant showed an increase in most proteogenic amino acids, phospholipids, and sphingolipids and higher fatty acid desaturase Ole1p content. Low glycolytic activity was behind the reduced growth and fermentative capacity of the thioredoxin deletion strain. All three hexokinases were downregulated in the mutant strain, but total hexokinase activity remained, probably due to posttranslational regulation. Pyruvate kinase Cdc19p presented an early level of aggregation in the Δ Δ mutant, which may contribute to a diminished hexose metabolism and trigger regulatory mechanisms that could influence the level of glycolytic enzymes. Oxidative stress is a common hazardous condition that cells have to face in their lifetime. Oxidative damage may diminish cell vitality and viability by reducing metabolism and eventually leading to aging and ultimate death. Wine yeast also faces oxidative attack during its biotechnological uses. One of the main yeast antioxidant systems involves two small proteins called thioredoxins. When these two proteins are removed, wine yeast shows diminished growth, protein synthesis, and sugar metabolism under wine-making conditions, and amino acid and lipid metabolism are also affected. Altogether, our results indicate that proper redox regulation is a key factor for metabolic adaptations during grape juice fermentation.
Topics: Cytosol; Fermentation; Gene Deletion; Glycolysis; Lipid Metabolism; Membrane Proteins; Metabolomics; Oxidation-Reduction; Oxidative Stress; Peroxiredoxins; Protein Biosynthesis; Proteomics; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Thioredoxins; Vitis; Wine
PubMed: 30683739
DOI: 10.1128/AEM.02953-18 -
Expert Opinion on Drug Metabolism &... Jul 2012The xenobiotic detoxification system, which protects the human body from external chemicals, comprises drug-metabolizing enzymes and transporters whose expressions are... (Review)
Review
INTRODUCTION
The xenobiotic detoxification system, which protects the human body from external chemicals, comprises drug-metabolizing enzymes and transporters whose expressions are regulated by pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). The progress made in a large number of recent studies calls for a timely review to summarize and highlight these key discoveries.
AREAS COVERED
This review summarizes recent advances in elucidating the roles of PXR and CAR in the xenobiotic detoxification system. It also highlights the progress in understanding the regulation of PXR and CAR activity at the post-translational levels, as well as the structural basis for the regulation of these two xenobiotic sensors.
EXPERT OPINION
Future efforts are needed to discover novel agonists and antagonists with species and isoform selectivity, to systematically understand the regulation of PXR and CAR at multiple levels (transcriptional, post-transcriptional and post-translational levels) in response to xenobiotics exposure, and to solve the structures of the full-length receptors, which will be enabled by improved protein expression and purification techniques and approaches. In addition, more efforts will be needed to validate PXR and CAR as disease-related therapeutic targets and thus expand their roles as master xenobiotic sensors.
Topics: Animals; Constitutive Androstane Receptor; Drug Interactions; Gene Expression Regulation; Humans; Inactivation, Metabolic; Ligands; Models, Animal; Pregnane X Receptor; Protein Binding; Protein Processing, Post-Translational; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Signal Transduction; Xenobiotics
PubMed: 22554043
DOI: 10.1517/17425255.2012.685237 -
Molecular Cancer Sep 2018In contrast to normal cells, which use the aerobic oxidation of glucose as their main energy production method, cancer cells prefer to use anaerobic glycolysis to... (Review)
Review
In contrast to normal cells, which use the aerobic oxidation of glucose as their main energy production method, cancer cells prefer to use anaerobic glycolysis to maintain their growth and survival, even under normoxic conditions. Such tumor cell metabolic reprogramming is regulated by factors such as hypoxia and the tumor microenvironment. In addition, dysregulation of certain signaling pathways also contributes to cancer metabolic reprogramming. Among them, the Hippo signaling pathway is a highly conserved tumor suppressor pathway. The core oncosuppressive kinase cascade of Hippo pathway inhibits the nuclear transcriptional co-activators YAP and TAZ, which are the downstream effectors of Hippo pathway and oncogenic factors in many solid cancers. YAP/TAZ function as key nodes of multiple signaling pathways and play multiple regulatory roles in cancer cells. However, their roles in cancer metabolic reprograming are less clear. In the present review, we examine progress in research into the regulatory mechanisms of YAP/TAZ on glucose metabolism, fatty acid metabolism, mevalonate metabolism, and glutamine metabolism in cancer cells. Determining the roles of YAP/TAZ in tumor energy metabolism, particularly in relation to the tumor microenvironment, will provide new strategies and targets for the selective therapy of metabolism-related cancers.
Topics: Cell Cycle Proteins; Cell Hypoxia; Energy Metabolism; Gluconeogenesis; Glycolysis; Humans; Intracellular Signaling Peptides and Proteins; Neoplasms; Nuclear Proteins; Signal Transduction; Trans-Activators; Transcription Factors; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Tumor Microenvironment
PubMed: 30176928
DOI: 10.1186/s12943-018-0882-1