scholarly journals Nutrient Sensing and Redox Balance: GCN2 as a New Integrator in Aging

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Paulina Falcón ◽  
Marcela Escandón ◽  
Álvaro Brito ◽  
Soledad Matus
Keyword(s):  
Stress Responses ◽  
Redox Balance ◽  
Nutritional Stress ◽  
Nutrient Sensing ◽  
Cellular Processes ◽  
Complex Process ◽  
Probability Of Death ◽  
Stress Sensing ◽  
Amino Acid Sensing

Aging is a complex process in which the accumulation of molecular, cellular, and organism dysfunction increases the probability of death. Several pieces of evidence have revealed a contribution of stress responses in aging and in aging-related diseases, in particular, the key role of signaling pathways associated to nutritional stress. Here, we review the possible interplay between amino acid sensing and redox balance maintenance mediated by the nutritional sensor general control nonderepressive 2 (GCN2). We discuss this new dimension of nutritional stress sensing consequences, standing out GCN2 as a central coordinator of key cellular processes that assure healthy homeostasis in the cell, raising GCN2 as a novel interesting target, that when activated, could imply pleiotropic benefits, particularly GCN2 intervention and its new unexplored therapeutic role as a player in the aging process.

scholarly journals Mitochondrial Sirtuins in Reproduction

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1047
Author(s):  
Giovanna Di Emidio ◽  
Stefano Falone ◽  
Paolo Giovanni Artini ◽  
Fernanda Amicarelli ◽  
Anna Maria D’Alessandro ◽  
...  
Keyword(s):  
Stress Responses ◽  
Metabolic Pathways ◽  
Redox Balance ◽  
Antioxidant Defenses ◽  
Metabolic Abnormalities ◽  
Female Reproduction ◽  
Mitochondrial Dysfunctions ◽  
Early Embryos ◽  
The Relationship

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.

scholarly journals Usp14 is required for spermatogenesis and ubiquitin stress responses in Drosophila melanogaster

2019 ◽  
Author(s):  
Levente Kovács ◽  
Ágota Nagy ◽  
Margit Pál ◽  
Peter Deák
Keyword(s):  
Male Sterility ◽  
Stress Responses ◽  
Expression Patterns ◽  
Loss Of Function ◽  
Wild Type ◽  
Cellular Processes ◽  
Protein Conjugates ◽  
Covalently Linked ◽  
Mutant Phenotypes

ABSTRACTDeubiquitinating (DUB) enzymes free covalently linked ubiquitins from ubiquitin-ubiquitin and ubiquitin-protein conjugates, and thereby maintain the equilibrium between free and conjugated ubiquitins and regulate ubiquitin-mediated cellular processes. The present genetic analyses of mutant phenotypes demonstrate that loss of Usp14 function results in male sterility, with defects in spermatid individualization and reduced testicular free monoubiquitin levels. These phenotypes were rescued by germline specific overexpression of wild type Usp14. Synergistic genetic interactions with Ubi-p63E and cycloheximide sensitivity suggest that ubiquitin shortage is a primary cause of male sterility. In addition, Usp14 is predominantly expressed in testes in Drosophila, and differential expression patterns may be causative of testis-specific loss of function Usp14 phenotypes. Collectively, these results suggest a major role of Usp14 in maintaining normal steady state free monoubiquitin levels during the later stages of Drosophila spermatogenesis.

scholarly journals Ethylene: A Master Regulator of Salinity Stress Tolerance in Plants

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 959 ◽  
Author(s):  
Riyazuddin Riyazuddin ◽  
Radhika Verma ◽  
Kalpita Singh ◽  
Nisha Nisha ◽  
Monika Keisham ◽  
...  
Keyword(s):  
Stress Tolerance ◽  
Salinity Stress ◽  
Cross Talk ◽  
Stress Responses ◽  
Antioxidant Defense ◽  
Growth And Yield ◽  
Ethylene Signaling ◽  
Cellular Processes ◽  
Salinity Stress Tolerance

Salinity stress is one of the major threats to agricultural productivity across the globe. Research in the past three decades, therefore, has focused on analyzing the effects of salinity stress on the plants. Evidence gathered over the years supports the role of ethylene as a key regulator of salinity stress tolerance in plants. This gaseous plant hormone regulates many vital cellular processes starting from seed germination to photosynthesis for maintaining the plants’ growth and yield under salinity stress. Ethylene modulates salinity stress responses largely via maintaining the homeostasis of Na+/K+, nutrients, and reactive oxygen species (ROS) by inducing antioxidant defense in addition to elevating the assimilation of nitrates and sulfates. Moreover, a cross-talk of ethylene signaling with other phytohormones has also been observed, which collectively regulate the salinity stress responses in plants. The present review provides a comprehensive update on the prospects of ethylene signaling and its cross-talk with other phytohormones to regulate salinity stress tolerance in plants.

scholarly journals Stress and ageing in yeast

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ian W Dawes ◽  
Gabriel G Perrone
Keyword(s):  
Yeast Cell ◽  
Cross Talk ◽  
Stress Responses ◽  
Cellular Responses ◽  
Ageing Process ◽  
Negative Effects ◽  
Beneficial Effects ◽  
Cellular Processes ◽  
Early Stress

ABSTRACT There has long been speculation about the role of various stresses in ageing. Some stresses have beneficial effects on ageing—dependent on duration and severity of the stress, others have negative effects and the question arises whether these negative effects are causative of ageing or the result of the ageing process. Cellular responses to many stresses are highly coordinated in a concerted way and hence there is a great deal of cross-talk between different stresses. Here the relevant aspects of the coordination of stress responses and the roles of different stresses on yeast cell ageing are discussed, together with the various functions that are involved. The cellular processes that are involved in alleviating the effects of stress on ageing are considered, together with the possible role of early stress events on subsequent ageing of cells.

scholarly journals Multilevel Regulation of Peroxisomal Proteome by Post-Translational Modifications

2019 ◽  
Vol 20 (19) ◽  
pp. 4881 ◽  
Author(s):  
Luisa M. Sandalio ◽  
Cecilia Gotor ◽  
Luis C. Romero ◽  
Maria C. Romero-Puertas
Keyword(s):  
Stress Responses ◽  
Environmental Changes ◽  
Glyoxylate Cycle ◽  
Regulation Of Gene Expression ◽  
Redox Balance ◽  
Polyamine Metabolism ◽  
Post Translational Modifications ◽  
Complex Process ◽  
The Glyoxylate Cycle ◽  
Multilevel Regulation

Peroxisomes, which are ubiquitous organelles in all eukaryotes, are highly dynamic organelles that are essential for development and stress responses. Plant peroxisomes are involved in major metabolic pathways, such as fatty acid β-oxidation, photorespiration, ureide and polyamine metabolism, in the biosynthesis of jasmonic, indolacetic, and salicylic acid hormones, as well as in signaling molecules such as reactive oxygen and nitrogen species (ROS/RNS). Peroxisomes are involved in the perception of environmental changes, which is a complex process involving the regulation of gene expression and protein functionality by protein post-translational modifications (PTMs). Although there has been a growing interest in individual PTMs in peroxisomes over the last ten years, their role and cross-talk in the whole peroxisomal proteome remain unclear. This review provides up-to-date information on the function and crosstalk of the main peroxisomal PTMs. Analysis of whole peroxisomal proteomes shows that a very large number of peroxisomal proteins are targeted by multiple PTMs, which affect redox balance, photorespiration, the glyoxylate cycle, and lipid metabolism. This multilevel PTM regulation could boost the plasticity of peroxisomes and their capacity to regulate metabolism in response to environmental changes.

scholarly journals mTORC1 as the main gateway to autophagy

2017 ◽  
Vol 61 (6) ◽  
pp. 565-584 ◽  
Author(s):  
Yoana Rabanal-Ruiz ◽  
Elsje G. Otten ◽  
Viktor I. Korolchuk
Keyword(s):  
Amino Acids ◽  
Nutrient Sensing ◽  
Biomedical Sciences ◽  
Energy Sensor ◽  
As Stress ◽  
Amino Acid Sensing ◽  
Amp Activated Protein Kinase ◽  
Cellular Components ◽  
Synthesis And Degradation

Cells and organisms must coordinate their metabolic activity with changes in their environment to ensure their growth only when conditions are favourable. In order to maintain cellular homoeostasis, a tight regulation between the synthesis and degradation of cellular components is essential. At the epicentre of the cellular nutrient sensing is the mechanistic target of rapamycin complex 1 (mTORC1) which connects environmental cues, including nutrient and growth factor availability as well as stress, to metabolic processes in order to preserve cellular homoeostasis. Under nutrient-rich conditions mTORC1 promotes cell growth by stimulating biosynthetic pathways, including synthesis of proteins, lipids and nucleotides, and by inhibiting cellular catabolism through repression of the autophagic pathway. Its close signalling interplay with the energy sensor AMP-activated protein kinase (AMPK) dictates whether the cell actively favours anabolic or catabolic processes. Underlining the role of mTORC1 in the coordination of cellular metabolism, its deregulation is linked to numerous human diseases ranging from metabolic disorders to many cancers. Although mTORC1 can be modulated by a number of different inputs, amino acids represent primordial cues that cannot be compensated for by any other stimuli. The understanding of how amino acids signal to mTORC1 has increased considerably in the last years; however this area of research remains a hot topic in biomedical sciences. The current ideas and models proposed to explain the interrelationship between amino acid sensing, mTORC1 signalling and autophagy is the subject of the present review.

scholarly journals Effect of Nutritional Stress on the Expression of Sirtuin Gene Family

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 124-124
Author(s):  
Xiaomin Zhang ◽  
Fathima Ameer ◽  
Jasmine Crane ◽  
Gohar Azhar ◽  
Jeanne Wei
Keyword(s):  
Stress Responses ◽  
Stress Conditions ◽  
Pcr Analysis ◽  
Diabetic Patients ◽  
Insulin Resistant ◽  
Cellular Processes ◽  
Low Glucose ◽  
C2c12 Muscle Cells ◽  
Growth And Aging

Abstract The sirtuin (SIRT) proteins are a highly conserved family of NAD+-dependent deacetylases that regulate histones as well as non-histone proteins. Seven sirtuin genes have been identified (SIRT1 to SIRT7) in mammals. SIRT1, SIRT6, and SIRT7 are primarily localized in the nucleus. SIRT2 is localized mainly in the cytoplasm. SIRT3, SIRT4, and SIRT5 are often located in the mitochondria. Therefore, the sirtuin family proteins exert their diverse functions at various cellular locations and regulate metabolism, stress responses, growth and aging processes. The sirtuin proteins are often considered as nutrient sensors. This study assessed the expression of sirtuin genes in C2C12 muscle cells under glucose stress conditions at different time points. Expression of all seven sirtuins was confirmed by Real-Time PCR analysis. SIRT1 (24 h) and SIRT3 (6 h and 15 h) are highly expressed under low glucose (2.7 mM) and high glucose (25 mM) conditions, whereas SIRT2 and SIRT4, SIRT5, SIRT6 and SIRT7 expressions were either relatively lower or there was no significant change under glucose stress conditions. Our results indicate that SIRT1 and SIRT3 demonstrated the greatest fluctuation in response to glucose stress, whether high or low glucose. These findings will help elucidate the role of sirtuins in the regulation of cellular processes, including metabolism. It will also help to enhance our understanding of the roles of sirtuin genes in regulation of blood sugar fluctuation in normal persons and diabetic patients, as well as in elderly individuals, many of whom are insulin resistant and “prediabetic” or diabetic.

scholarly journals mTOR and Aging: An Old Fashioned Dress

2019 ◽  
Vol 20 (11) ◽  
pp. 2774 ◽  
Author(s):  
Giovanni Stallone ◽  
Barbara Infante ◽  
Concetta Prisciandaro ◽  
Giuseppe Grandaliano
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Nutrient Sensing ◽  
Protective Effects ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Age Related ◽  
Signalling Network ◽  
Evolutionarily Conserved ◽  
Mtor Signalling

Aging is a physiologic/pathologic process characterized by a progressive impairment of cellular functions, supported by the alterations of several molecular pathways, leading to an increased cell susceptibility to injury. This deterioration is the primary risk factor for several major human pathologies. Numerous cellular processes, including genomic instability, telomere erosion, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, stem cell exhaustion, and altered intercellular signal transduction represent common denominators of aging in different organisms. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved nutrient sensing protein kinase that regulates growth and metabolism in all eukaryotic cells. Studies in flies, worms, yeast, and mice support the hypothesis that the mTOR signalling network plays a pivotal role in modulating aging. mTOR is emerging as the most robust mediator of the protective effects of various forms of dietary restriction, which has been shown to extend lifespan and slow the onset of age-related diseases across species. Herein we discuss the role of mTor signalling network in the development of classic age-related diseases, focused on cardiovascular system, immune response, and cancer.

scholarly journals The Importance of Protein Phosphorylation for Signaling and Metabolism in Response to Diel Light Cycling and Nutrient Availability in a Marine Diatom

Biology ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 155
Author(s):  
Maxine H. Tan ◽  
Sarah R. Smith ◽  
Kim K. Hixson ◽  
Justin Tan ◽  
James K. McCarthy ◽  
...  
Keyword(s):  
Protein Phosphorylation ◽  
Nitrogen Availability ◽  
Stress Proteins ◽  
Nutrient Sensing ◽  
Marine Diatom ◽  
Diel Cycle ◽  
Phosphorylation Sites ◽  
Cellular Processes ◽  
Phosphorylated Peptides

Diatoms are major contributors to global primary production and their populations in the modern oceans are affected by availability of iron, nitrogen, phosphate, silica, and other trace metals, vitamins, and infochemicals. However, little is known about the role of phosphorylation in diatoms and its role in regulation and signaling. We report a total of 2759 phosphorylation sites on 1502 proteins detected in Phaeodactylum tricornutum. Conditionally phosphorylated peptides were detected at low iron (n = 108), during the diel cycle (n = 149), and due to nitrogen availability (n = 137). Through a multi-omic comparison of transcript, protein, phosphorylation, and protein homology, we identify numerous proteins and key cellular processes that are likely under control of phospho-regulation. We show that phosphorylation regulates: (1) carbon retrenchment and reallocation during growth under low iron, (2) carbon flux towards lipid biosynthesis after the lights turn on, (3) coordination of transcription and translation over the diel cycle and (4) in response to nitrogen depletion. We also uncover phosphorylation sites for proteins that play major roles in diatom Fe sensing and utilization, including flavodoxin and phytotransferrin (ISIP2A), as well as identify phospho-regulated stress proteins and kinases. These findings provide much needed insight into the roles of protein phosphorylation in diel cycling and nutrient sensing in diatoms.

Sign in / Sign up

Export Citation Format

Share Document