Faculty Opinions recommendation of Default activation and nuclear translocation of the plant cellular energy sensor snrk1 regulate metabolic stress responses and development.

2019 ◽  
Author(s):  
Sjef Smeekens
Keyword(s):  
Stress Responses ◽  
Nuclear Translocation ◽  
Metabolic Stress ◽  
Cellular Energy ◽  
Energy Sensor

scholarly journals Default Activation and Nuclear Translocation of the Plant Cellular Energy Sensor SnRK1 Regulate Metabolic Stress Responses and Development

2019 ◽  
Vol 31 (7) ◽  
pp. 1614-1632 ◽  
Author(s):  
Matthew Ramon ◽  
Tuong Vi T. Dang ◽  
Tom Broeckx ◽  
Sander Hulsmans ◽  
Nathalie Crepin ◽  
...  
Keyword(s):  
Stress Responses ◽  
Nuclear Translocation ◽  
Metabolic Stress ◽  
Cellular Energy ◽  
Energy Sensor

MondoA Drives B-ALL Malignancy through Enhanced Adaptation to Metabolic Stress

Blood ◽  
2021 ◽  
Author(s):  
Alexandra Sipol ◽  
Erik Hameister ◽  
Busheng Xue ◽  
Julia Hofstetter ◽  
Maxim Barenboim ◽  
...  
Keyword(s):  
Stress Responses ◽  
Lymphoblastic Leukemia ◽  
Metabolic Stress ◽  
Tca Cycle ◽  
Underlying Mechanism ◽  
Patient Data ◽  
Data Sets ◽  
Dependent Manner

Cancer cells are in most instances characterized by rapid proliferation and uncontrolled cell division. Hence, they must adapt to proliferation-induced metabolic stress through intrinsic or acquired anti-metabolic stress responses to maintain homeostasis and survival. One mechanism to achieve this is to reprogram gene expression in a metabolism-dependent manner. MondoA (also known as MLXIP), a member of the MYC interactome, has been described as an example of such a metabolic sensor. However, the role of MondoA in malignancy is not fully understood and the underlying mechanism in metabolic responses remains elusive. By assessing patient data sets we found that MondoA overexpression is associated with a worse survival in pediatric common acute lymphoblastic leukemia (B-ALL). Using CRISPR/Cas9 and RNA interference approaches, we observed that MondoA depletion reduces transformational capacity of B-ALL cells in vitro and dramatically inhibits malignant potential in an in vivo mouse model. Interestingly, reduced expression of MondoA in patient data sets correlated with enrichment in metabolic pathways. The loss of MondoA correlated with increased tricarboxylic acid (TCA) cycle activity. Mechanistically, MondoA senses metabolic stress in B-ALL cells by restricting oxidative phosphorylation through reduced PDH activity. Glutamine starvation conditions greatly enhance this effect and highlight the inability to mitigate metabolic stress upon loss of MondoA in B-ALL. Our findings give a novel insight into the function of MondoA in pediatric B-ALL and support the notion that MondoA inhibition in this entity offers a therapeutic opportunity and should be further explored.

Emerging roles of endoplasmic reticulum-resident selenoproteins in the regulation of cellular stress responses and the implications for metabolic disease

2018 ◽  
Vol 475 (6) ◽  
pp. 1037-1057 ◽  
Author(s):  
Alex B. Addinsall ◽  
Craig R. Wright ◽  
Sof Andrikopoulos ◽  
Chris van der Poel ◽  
Nicole Stupka
Keyword(s):  
Metabolic Disease ◽  
Endoplasmic Reticulum ◽  
Stress Responses ◽  
Cellular Stress ◽  
Metabolic Stress ◽  
Metabolic Dysfunction ◽  
Iodothyronine Deiodinase ◽  
Inflammatory Stress ◽  
Cellular Stress Responses

Chronic metabolic stress leads to cellular dysfunction, characterized by excessive reactive oxygen species, endoplasmic reticulum (ER) stress and inflammation, which has been implicated in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. The ER is gaining recognition as a key organelle in integrating cellular stress responses. ER homeostasis is tightly regulated by a complex antioxidant system, which includes the seven ER-resident selenoproteins — 15 kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins S, N, K, M and T. Here, the findings from biochemical, cell-based and mouse studies investigating the function of ER-resident selenoproteins are reviewed. Human experimental and genetic studies are drawn upon to highlight the relevance of these selenoproteins to the pathogenesis of metabolic disease. ER-resident selenoproteins have discrete roles in the regulation of oxidative, ER and inflammatory stress responses, as well as intracellular calcium homeostasis. To date, only two of these ER-resident selenoproteins, selenoproteins S and N have been implicated in human disease. Nonetheless, the potential of all seven ER-resident selenoproteins to ameliorate metabolic dysfunction warrants further investigation.

Acute Impact of Recovery on the Restoration of Cellular Immunological Homeostasis

2019 ◽  
Vol 41 (01) ◽  
pp. 12-20 ◽  
Author(s):  
Patrick Wahl ◽  
Sebastian Mathes ◽  
Wilhelm Bloch ◽  
Philipp Zimmer
Keyword(s):  
Cell Count ◽  
Stress Responses ◽  
Metabolic Stress ◽  
Interval Training ◽  
Active Recovery ◽  
Mixed Cell ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Passive Recovery ◽  
Quick Recovery

AbstractIn view of the growing amount of (intense) training in competitive sports, quick recovery plays a superior role in performance restoration. The aim of the present study was to compare the effects of active versus passive recovery during high-intensity interval training (HIIT) and sprint interval training (SIT) protocols on acute alterations of circulating blood cells. Twelve male triathletes/cyclists performed 1) a HIIT consisting of 4×4 min intervals, 2) a SIT consisting of 4×30s intervals, separated by either active or passive recovery. Blood samples were collected immediately before and at 0’, 30’, 60’ and 180’ (minutes) post-exercise. Outcomes comprised leukocytes, lymphocytes, neutrophils, mixed cell count, platelets, cellular inflammation markers (neutrophil/lymphocyte-ratio (NLR), platelet/lymphocyte-ratio (PLR)), and the systemic immune-inflammation index (SII). In view of HIIT, passive recovery attenuated the changes in lymphocytes and neutrophils compared to active recovery. In view of SIT, active recovery attenuated the increase in leukocytes, lymphocytes and absolute mixed cell count compared to passive recovery. Both protocols, independent of recovery, significantly increased NLR, PLR and SII up to 3h of recovery compared to pre-exercise values. The mode of recovery influences short-term alterations in the circulating fraction of leukocytes, lymphocytes, neutrophils and the mixed cell count, which might be associated with different hormonal and metabolic stress responses due to the mode of recovery.

scholarly journals Activation of AMPK under Hypoxia: Many Roads Leading to Rome

2020 ◽  
Vol 21 (7) ◽  
pp. 2428 ◽  
Author(s):  
Franziska Dengler
Keyword(s):  
Current Knowledge ◽  
Protective Action ◽  
Energy Levels ◽  
Hypoxia Inducible Factor ◽  
Protective Effects ◽  
Ampk Activation ◽  
Cellular Energy ◽  
Energy Sensor ◽  
Atp Supply ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is known as a pivotal cellular energy sensor, mediating the adaptation to low energy levels by deactivating anabolic processes and activating catabolic processes in order to restore the cellular ATP supply when the cellular AMP/ATP ratio is increased. Besides this well-known role, it has also been shown to exert protective effects under hypoxia. While an insufficient supply with oxygen might easily deplete cellular energy levels, i.e., ATP concentration, manifold other mechanisms have been suggested and are heavily disputed regarding the activation of AMPK under hypoxia independently from cellular AMP concentrations. However, an activation of AMPK preceding energy depletion could induce a timely adaptation reaction preventing more serious damage. A connection between AMPK and the master regulator of hypoxic adaptation via gene transcription, hypoxia-inducible factor (HIF), has also been taken into account, orchestrating their concerted protective action. This review will summarize the current knowledge on mechanisms of AMPK activation under hypoxia and its interrelationship with HIF.

scholarly journals Sestrins at the Interface of ROS Control and Autophagy Regulation in Health and Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Marco Cordani ◽  
Miguel Sánchez-Álvarez ◽  
Raffaele Strippoli ◽  
Alexandr V. Bazhin ◽  
Massimo Donadelli
Keyword(s):  
Metabolic Disorders ◽  
Mammalian Target Of Rapamycin ◽  
Therapeutic Targets ◽  
Metabolic Stress ◽  
Dependent Protein Kinase ◽  
Energy Sensor ◽  
Positive Regulators ◽  
Dependent Protein ◽  
Health And Disease ◽  
Broad Interest

Reactive oxygen species (ROS) and autophagy are two highly complex and interrelated components of cell physiopathology, but our understanding of their integration and their contribution to cell homeostasis and disease is still limited. Sestrins (SESNs) belong to a family of highly conserved stress-inducible proteins that orchestrate antioxidant and autophagy-regulating functions protecting cells from various noxious stimuli, including DNA damage, oxidative stress, hypoxia, and metabolic stress. They are also relevant modulators of metabolism as positive regulators of the key energy sensor AMP-dependent protein kinase (AMPK) and inhibitors of mammalian target of rapamycin complex 1 (mTORC1). Since perturbations in these pathways are central to multiple disorders, SESNs might constitute potential novel therapeutic targets of broad interest. In this review, we discuss the current understanding of regulatory and effector networks of SESNs, highlighting their significance as potential biomarkers and therapeutic targets for different diseases, such as aging-related diseases, metabolic disorders, neurodegenerative diseases, and cancer.

scholarly journals Combating stress: the interplay between hormone signaling and autophagy in plants

2019 ◽  
Vol 71 (5) ◽  
pp. 1723-1733 ◽  
Author(s):  
Ching-Yi Liao ◽  
Diane C Bassham
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
Plant Stress ◽  
Stress Conditions ◽  
Hormone Signaling ◽  
Hormone Synthesis ◽  
Energy Sensor ◽  
Sensor Kinases ◽  
Plant Stress Responses ◽  
Cellular Components

Abstract Autophagy is a conserved recycling process in which cellular components are delivered to and degraded in the vacuole/lysosome for reuse. In plants, it assists in responding to dynamic environmental conditions and maintaining metabolite homeostasis under normal or stress conditions. Under stress, autophagy is activated to remove damaged components and to recycle nutrients for survival, and the energy sensor kinases target of rapamycin (TOR) and SNF-related kinase 1 (SnRK1) are key to this activation. Here, we discuss accumulating evidence that hormone signaling plays critical roles in regulating autophagy and plant stress responses, although the molecular mechanisms by which this occurs are often not clear. Several hormones have been shown to regulate TOR activity during stress, in turn controlling autophagy. Hormone signaling can also regulate autophagy gene expression, while, reciprocally, autophagy can regulate hormone synthesis and signaling pathways. We highlight how the interplay between major energy sensors, plant hormones, and autophagy under abiotic and biotic stress conditions can assist in plant stress tolerance.

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