SUMO, hypoxia and the regulation of metabolism

2008 ◽  
Vol 36 (3) ◽  
pp. 445-448 ◽  
Author(s):  
Terence A. Agbor ◽  
Cormac T. Taylor
Keyword(s):  
Cellular Response ◽  
Protein Modification ◽  
Critical Role ◽  
Critical Event ◽  
Post Translational Modification ◽  
Dynamic Regulation ◽  
Regulation Of Metabolism ◽  
Metabolic Challenge ◽  
Metabolic Regulators

Post-translational modification is a critical event in the dynamic regulation of protein stability, location, structure, function, activity and interaction with other proteins and as such plays an important role in organism complexity. Over the last 10 years, the extensive and critical role of one such protein modification by SUMO (small ubiquitin-related modifier) has become apparent. The focus of this mini-review will be on recent reports of a possible functional role for the SUMO pathway in the adaptive cellular response to metabolic challenge, such as oxygen deprivation (hypoxia). Here, we will briefly review the evolving evidence for this pathway in the regulation of a number of metabolic regulators and discuss a possible role for SUMOylation in the regulation of basic metabolic function.

Pathogenesis of Age-related Cataract: a systematic review of proteomic studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Christina Karakosta ◽  
Argyrios Tzamalis ◽  
Michalis Aivaliotis ◽  
Ioannis Tsinopoulos
Keyword(s):  
Systematic Review ◽  
Oxidant Stress ◽  
Critical Role ◽  
Human Lens ◽  
Nuclear Cataract ◽  
Cataract Formation ◽  
Post Translational Modification ◽  
Ability To Act ◽  
Age Related

Background/Objective:: The aim of this systematic review is to identify all the available data on human lens proteomics with a critical role to age-related cataract formation in order to elucidate the physiopathology of the aging lens. Materials and Methods:: We searched on Medline and Cochrane databases. The search generated 328 manuscripts. We included nine original proteomic studies that investigated human cataractous lenses. Results:: Deamidation was the major age-related post-translational modification. There was a significant increase in the amount of αA-crystallin D-isoAsp58 present at all ages, while an increase in the extent of Trp oxidation was apparent in cataract lenses when compared to aged normal lenses. During aging, enzymes with oxidized cysteine at critical sites included GAPDH, glutathione synthase, aldehyde dehydrogenase, sorbitol dehydrogenase, and PARK7. Conclusion:: D-isoAsp in αA crystallin could be associated with the development of age-related cataract in human, by contributing to the denaturation of a crystallin, and decreasing its ability to act as a chaperone. Oxidation of Trp may be associated with nuclear cataract formation in human, while the role of oxidant stress in age-related cataract formation is dominant.

scholarly journals The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking

2009 ◽  
Vol 187 (7) ◽  
pp. 1101-1116 ◽  
Author(s):  
Chiara Francavilla ◽  
Paola Cattaneo ◽  
Vladimir Berezin ◽  
Elisabeth Bock ◽  
Diletta Ami ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cellular Response ◽  
Critical Role ◽  
Biological Significance ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Fgf Receptor ◽  
Neural Cell Adhesion ◽  
Sustained Activation

Neural cell adhesion molecule (NCAM) associates with fibroblast growth factor (FGF) receptor-1 (FGFR1). However, the biological significance of this interaction remains largely elusive. In this study, we show that NCAM induces a specific, FGFR1-mediated cellular response that is remarkably different from that elicited by FGF-2. In contrast to FGF-induced degradation of endocytic FGFR1, NCAM promotes the stabilization of the receptor, which is recycled to the cell surface in a Rab11- and Src-dependent manner. In turn, FGFR1 recycling is required for NCAM-induced sustained activation of various effectors. Furthermore, NCAM, but not FGF-2, promotes cell migration, and this response depends on FGFR1 recycling and sustained Src activation. Our results implicate NCAM as a nonconventional ligand for FGFR1 that exerts a peculiar control on the intracellular trafficking of the receptor, resulting in a specific cellular response. Besides introducing a further level of complexity in the regulation of FGFR1 function, our findings highlight the link of FGFR recycling with sustained signaling and cell migration and the critical role of these events in dictating the cellular response evoked by receptor activation.

scholarly journals The Contribution of Astrocyte Autophagy to Systemic Metabolism

2020 ◽  
Vol 21 (7) ◽  
pp. 2479
Author(s):  
Ana Ortiz-Rodriguez ◽  
Maria-Angeles Arevalo
Keyword(s):  
Saturated Fatty Acids ◽  
Brain Inflammation ◽  
Central Regulation ◽  
Feeding Response ◽  
Regulation Of Metabolism ◽  
Body Energy ◽  
Metabolic Regulators ◽  
Brain Homeostasis

Autophagy is an essential mechanism to maintain cellular homeostasis. Besides its role in controlling the quality of cytoplasmic components, it participates in nutrient obtaining and lipid mobilization under stressful conditions. Furthermore, autophagy is involved in the regulation of systemic metabolism as its blockade in hypothalamic neurons can affect the central regulation of metabolism and impact body energy balance. Moreover, hypothalamic autophagy can be altered during obesity, one of the main alterations of metabolism nowadays. In this review, we focus on the role of astrocytes, essential cells for brain homeostasis, which represent key metabolic regulators. Astrocytes can sense metabolic signals in the hypothalamus and modulate systemic functions as glucose homeostasis and feeding response. Moreover, the response of astrocytes to obesity has been widely studied. Astrocytes are important mediators of brain inflammation and can be affected by increased levels of saturated fatty acids associated with obesity. Although autophagy plays important roles for astrocyte homeostasis and functioning, the contribution of astrocyte autophagy to systemic metabolism has not been analyzed yet. Furthermore, how obesity can impact astrocyte autophagy is poorly understood. More studies are needed in order to understand the contribution of astrocyte autophagy to metabolism.

scholarly journals Neddylation is critical to cortical development by regulating Wnt/β-catenin signaling

2020 ◽  
Vol 117 (42) ◽  
pp. 26448-26459 ◽  
Author(s):  
Lei Zhang ◽  
Hongyang Jing ◽  
Haiwen Li ◽  
Wenbing Chen ◽  
Bin Luo ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Protein Modification ◽  
Radial Glia ◽  
Critical Role ◽  
Cortical Development ◽  
Nuclear Accumulation ◽  
Progressive Reduction ◽  
Intermediate Progenitors

Wnt signaling plays a critical role in production and differentiation of neurons and undergoes a progressive reduction during cortical development. However, how Wnt signaling is regulated is not well understood. Here we provide evidence for an indispensable role of neddylation, a ubiquitylation-like protein modification, in inhibiting Wnt/β-catenin signaling. We show that β-catenin is neddylated; and inhibiting β-catenin neddylation increases its nuclear accumulation and Wnt/β-catenin signaling. To test this hypothesis in vivo, we mutated Nae1, an obligative subunit of the E1 for neddylation in cortical progenitors. The mutation leads to eventual reduction in radial glia progenitors (RGPs). Consequently, the production of intermediate progenitors (IPs) and neurons is reduced, and neuron migration is impaired, resulting in disorganization of the cerebral cortex. These phenotypes are similar to those of β-catenin gain-of-function mice. Finally, suppressing β-catenin expression is able to rescue deficits of Nae1 mutant mice. Together, these observations identified a mechanism to regulate Wnt/β-catenin signaling in cortical development.

scholarly journals Telomeres, stem cells, and hematology

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 1759-1766 ◽  
Author(s):  
Peter M. Lansdorp
Keyword(s):  
Stem Cells ◽  
Telomere Length ◽  
Cellular Response ◽  
Germ Line ◽  
Critical Role ◽  
Somatic Cells ◽  
Growth Stimulation ◽  
Critical Function ◽  
Telomere Attrition

Telomeres are highly dynamic structures that adjust the cellular response to stress and growth stimulation based on previous cell divisions. This critical function is accomplished by progressive telomere shortening and DNA damage responses activated by chromosome ends without sufficient telomere repeats. Repair of critically short telomeres by telomerase or recombination is limited in most somatic cells, and apoptosis or cellular senescence is triggered when too many uncapped telomeres accumulate. The chance of the latter increases as the average telomere length decreases. The average telomere length is set and maintained in cells of the germ line that typically express high levels of telomerase. In somatic cells, the telomere length typically declines with age, posing a barrier to tumor growth but also contributing to loss of cells with age. Loss of (stem) cells via telomere attrition provides strong selection for abnormal cells in which malignant progression is facilitated by genome instability resulting from uncapped telomeres. The critical role of telomeres in cell proliferation and aging is illustrated in patients with 50% of normal telomerase levels resulting from a mutation in one of the telomerase genes. Here, the role of telomeres and telomerase in human biology is reviewed from a personal historical perspective.

scholarly journals In vivo vizualisation of mono-ADP-ribosylation by dPARP16 upon amino-acid starvation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Angelica Aguilera-Gomez ◽  
Marinke M van Oorschot ◽  
Tineke Veenendaal ◽  
Catherine Rabouille
Keyword(s):  
Amino Acid ◽  
Metabolic Stress ◽  
Amino Acid Starvation ◽  
Critical Event ◽  
Post Translational Modification ◽  
Adp Ribosylation ◽  
Body Component ◽  
Necessary And Sufficient

PARP catalysed ADP-ribosylation is a post-translational modification involved in several physiological and pathological processes, including cellular stress. In order to visualise both Poly-, and Mono-, ADP-ribosylation in vivo, we engineered specific fluorescent probes. Using them, we show that amino-acid starvation triggers an unprecedented display of mono-ADP-ribosylation that governs the formation of Sec body, a recently identified stress assembly that forms in Drosophila cells. We show that dPARP16 catalytic activity is necessary and sufficient for both amino-acid starvation induced mono-ADP-ribosylation and subsequent Sec body formation and cell survival. Importantly, dPARP16 catalyses the modification of Sec16, a key Sec body component, and we show that it is a critical event for the formation of this stress assembly. Taken together our findings establish a novel example for the role of mono-ADP-ribosylation in the formation of stress assemblies, and link this modification to a metabolic stress.

scholarly journals Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal

2009 ◽  
Vol 424 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Bradford G. Hill ◽  
Brian P. Dranka ◽  
Luyun Zou ◽  
John C. Chatham ◽  
Victor M. Darley-Usmar
Keyword(s):  
Cell Death ◽  
Cellular Response ◽  
Protein Modification ◽  
Ventricular Myocytes ◽  
Critical Role ◽  
Reserve Capacity ◽  
Energy Demands ◽  
Lipid Species ◽  
Cellular Context ◽  
Response To Stress

Mitochondria play a critical role in mediating the cellular response to oxidants formed during acute and chronic cardiac dysfunction. It is widely assumed that, as cells are subjected to stress, mitochondria are capable of drawing upon a ‘reserve capacity’ which is available to serve the increased energy demands for maintenance of organ function, cellular repair or detoxification of reactive species. This hypothesis further implies that impairment or depletion of this putative reserve capacity ultimately leads to excessive protein damage and cell death. However, it has been difficult to fully evaluate this hypothesis since much of our information about the response of the mitochondrion to oxidative stress derives from studies on mitochondria isolated from their cellular context. Therefore the goal of the present study was to determine whether ‘bioenergetic reserve capacity’ does indeed exist in the intact myocyte and whether it is utilized in response to stress induced by the pathologically relevant reactive lipid species HNE (4-hydroxynonenal). We found that intact rat neonatal ventricular myocytes exhibit a substantial bioenergetic reserve capacity under basal conditions; however, on exposure to pathologically relevant concentrations of HNE, oxygen consumption was increased until this reserve capacity was depleted. Exhaustion of the reserve capacity by HNE treatment resulted in inhibition of respiration concomitant with protein modification and cell death. These data suggest that oxidized lipids could contribute to myocyte injury by decreasing the bioenergetic reserve capacity. Furthermore, these studies demonstrate the utility of measuring the bioenergetic reserve capacity for assessing or predicting the response of cells to stress.

scholarly journals Critical Role of H2O2 Generated by NOX4 during Cellular Response under Glucose Deprivation

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e56628 ◽  
Author(s):  
Satoshi Owada ◽  
Yuko Shimoda ◽  
Katsuya Tsuchihara ◽  
Hiroyasu Esumi
Keyword(s):  
Cellular Response ◽  
Critical Role ◽  
Glucose Deprivation

scholarly journals Comparative Analysis Based on Transcriptomics and Metabolomics Data Reveal Differences between Emmer and Durum Wheat in Response to Nitrogen Starvation

2021 ◽  
Vol 22 (9) ◽  
pp. 4790
Author(s):  
Romina Beleggia ◽  
Nooshin Omranian ◽  
Yan Holtz ◽  
Tania Gioia ◽  
Fabio Fiorani ◽  
...  
Keyword(s):  
Durum Wheat ◽  
Critical Role ◽  
Tetraploid Wheat ◽  
Enrichment Analysis ◽  
Specific Response ◽  
Metabolomics Data ◽  
Glutamate Signaling ◽  
Regulation Of Metabolism ◽  
N Starvation

Mounting evidence indicates the key role of nitrogen (N) on diverse processes in plant, including development and defense. Using a combined transcriptomics and metabolomics approach, we studied the response of seedlings to N starvation of two different tetraploid wheat genotypes from the two main domesticated subspecies: emmer and durum wheat. We found that durum wheat exhibits broader and stronger response in comparison to emmer as seen from the expression pattern of both genes and metabolites and gene enrichment analysis. They showed major differences in the responses to N starvation for transcription factor families, emmer showed differential reduction in the levels of primary metabolites while durum wheat exhibited increased levels of most of them to N starvation. The correlation-based networks, including the differentially expressed genes and metabolites, revealed tighter regulation of metabolism in durum wheat in comparison to emmer. We also found that glutamate and -aminobutyric acid (GABA) had highest values of centrality in the metabolic correlation network, suggesting their critical role in the genotype-specific response to N starvation of emmer and durum wheat, respectively. Moreover, this finding indicates that there might be contrasting strategies associated to GABA and glutamate signaling modulating shoot vs. root growth in the two different wheat subspecies.

scholarly journals Importance of tyrosine phosphorylation for transmembrane signaling in plants

2021 ◽  
Vol 478 (14) ◽  
pp. 2759-2774
Author(s):  
Henning Mühlenbeck ◽  
Kyle W. Bender ◽  
Cyril Zipfel
Keyword(s):  
Plant Immunity ◽  
Critical Role ◽  
Sh2 Domain ◽  
Receptor Kinase ◽  
Post Translational Modification ◽  
The Core ◽  
Domains Of Life ◽  
Reversible Protein Phosphorylation ◽  
Signaling Modules

Reversible protein phosphorylation is a widespread post-translational modification fundamental for signaling across all domains of life. Tyrosine (Tyr) phosphorylation has recently emerged as being important for plant receptor kinase (RK)-mediated signaling, particularly during plant immunity. How Tyr phosphorylation regulates RK function is however largely unknown. Notably, the expansion of protein Tyr phosphatase and SH2 domain-containing protein families, which are the core of regulatory phospho-Tyr (pTyr) networks in choanozoans, did not occur in plants. Here, we summarize the current understanding of plant RK Tyr phosphorylation focusing on the critical role of a pTyr site (‘VIa-Tyr’) conserved in several plant RKs. Furthermore, we discuss the possibility of metazoan-like pTyr signaling modules in plants based on atypical components with convergent biochemical functions.

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