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Marina Villanueva Paz, David Cotán, Juan Garrido Maraver, Manuel Oropesa-Ávila, Mario de la Mata, Ana Delgado Pavón, Isabel de Lavera, Elizabet Alcocer Gómez, Mónica Álvarez Córdoba, José A Sánchez Alcázar
No abstract text is available yet for this article.
2016: EXS
Martin Pelosse, Cécile Cottet-Rousselle, Alexei Grichine, Imre Berger, Uwe Schlattner
Maintenance of energy homeostasis is a basic requirement for cell survival. Different mechanisms have evolved to cope with spatial and temporal mismatch between energy-providing and -consuming processes. Among these, signaling by AMP-activated protein kinase (AMPK) is one of the key players, regulated by and itself regulating cellular adenylate levels. Further understanding its complex cellular function requires deeper insight into its activation patterns in space and time at a single cell level. This may become possible with an increasing number of genetically encoded fluorescent biosensors, mostly based on fluorescence resonance energy transfer, which have been engineered to monitor metabolic parameters and kinase activities...
2016: EXS
Xiaoqing Zhu, J Willem Voncken, Dietbert Neumann
AMPK studies in cell-free and cellular systems have significantly contributed to recent progress in the AMPK field. Biochemical characterization, structure determination and elucidation of AMPK-dependent signalling events benefit from application of state-of-the-art tools and methodology. This chapter provides a synopsis of recombinant protein expression systems and biochemical and cell-based study methods. We summarize three different expression systems for AMPK production: bacteria, insect cells and mammalian cells...
2016: EXS
Benoit Viollet, Marc Foretz
AMPK is an evolutionary conserved energy sensor involved in the regulation of energy metabolism. Based on biochemical studies, AMPK has brought much of interest in recent years due to its potential impact on metabolic disorders. Suitable animal models are therefore essential to promote our understanding of the molecular and functional roles of AMPK but also to bring novel information for the development of novel therapeutic strategies. The organism systems include pig (Sus scrofa), mouse (Mus musculus), fly (Drosophila melanogaster), worm (Caenorhabditis elegans), and fish (Danio rerio) models...
2016: EXS
Leonor Margalha, Concetta Valerio, Elena Baena-González
SnRK1 is an evolutionarily conserved protein kinase complex that regulates energy homeostasis in plants. In doing so, it promotes tolerance to adverse environmental conditions and influences a large array of growth and developmental processes. SnRK1 shares clear structural and functional similarities with its orthologs, yeast SNF1 and mammalian AMPK, but has evolved unique features that presumably provide a better adaptation to an autotrophic lifestyle. In this chapter, we review current knowledge on SnRK1, an atypical member of the SNF1/AMPK family, providing insight into its structure, regulation, and functions...
2016: EXS
Sarah E Sinnett, Jay E Brenman
In the fruit fly, Drosophila melanogaster, mono-allelic expression of AMPK-α, -β, and -γ yields a single heterotrimeric energy sensor that regulates cellular and whole-body energetic homeostasis. The genetic simplicity of Drosophila, with only a single gene for each subunit, makes the fruit fly an appealing organism for elucidating the effects of AMPK mutations on signaling pathways and phenotypes. In addition, Drosophila presents researchers with an opportunity to use straightforward genetic approaches to elucidate metabolic signaling pathways that contain a level of complexity similar to that observed in mammalian pathways...
2016: EXS
Moloud Ahmadi, Richard Roy
AMP-activated protein kinase (AMPK) is one of the central regulators of cellular and organismal metabolism in eukaryotes. Once activated by decreased energy levels, it induces ATP production by promoting catabolic pathways while conserving ATP by inhibiting anabolic pathways. AMPK plays a crucial role in various aspects of cellular function such as regulating growth, reprogramming metabolism, autophagy, and cell polarity. In this chapter, we focus on how recent breakthroughs made using the model organism Caenorhabditis elegans have contributed to our understanding of AMPK function and how it can be utilized in the future to elucidate hitherto unknown aspects of AMPK signaling...
2016: EXS
Pascual Sanz, Rosa Viana, Maria Adelaida Garcia-Gimeno
In yeast, SNF1 protein kinase is the orthologue of mammalian AMPK complex. It is a trimeric complex composed of Snf1 protein kinase (orthologue of AMPKα catalytic subunit), Snf4 (orthologue of AMPKγ regulatory subunit), and a member of the Gal83/Sip1/Sip2 family of proteins (orthologues of AMPKβ subunit) that act as scaffolds and also regulate the subcellular localization of the complex. In this chapter, we review the recent literature on the characteristics of SNF1 complex subunits, the structure and regulation of the activity of the SNF1 complex, its role at the level of transcriptional regulation of relevant target genes and also at the level of posttranslational modification of targeted substrates...
2016: EXS
Bruno Guigas, Benoit Viollet
The AMP-activated protein kinase (AMPK) is an evolutionary conserved and ubiquitously expressed serine/threonine kinase mainly acting as a key regulator of cellular energy homeostasis. AMPK is a heterotrimeric protein complex, consisting of a catalytic α subunit and two regulatory β and γ subunits, whose activity is tightly regulated by changes in adenine nucleotides and several posttranslational modifications. Once activated in response to energy deficit, AMPK concomitantly inhibits ATP-consuming anabolic processes and promotes ATP-generating catabolic pathways via direct phosphorylation of multiple downstream effectors, leading to restoration of cellular energy balance...
2016: EXS
Inês Mesquita, Diana Moreira, Belém Sampaio-Marques, Mireille Laforge, Anabela Cordeiro-da-Silva, Paula Ludovico, Jérôme Estaquier, Ricardo Silvestre
During host-pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Among these, subversion of host cell energy metabolism by pathogens is currently recognized to play an important role in microbial growth and persistence...
2016: EXS
Marina N Asiedu, Gregory Dussor, Theodore J Price
Chronic pain is a major clinical problem that is poorly treated with available therapeutics. Adenosine monophosphate-activated protein kinase (AMPK) has recently emerged as a novel target for the treatment of pain with the exciting potential for disease modification. AMPK activators inhibit signaling pathways that are known to promote changes in the function and phenotype of peripheral nociceptive neurons and promote chronic pain. AMPK activators also reduce the excitability of these cells suggesting that AMPK activators may be efficacious for the treatment of chronic pain disorders, like neuropathic pain, where changes in the excitability of nociceptors is thought to be an underlying cause...
2016: EXS
Kristopher Burkewitz, Heather J M Weir, William B Mair
Chronic, age-associated diseases are already among the leading causes of morbidity and death in the world, a problem exacerbated by the rapidly rising proportion of elderly in the global population. This emergent epidemic represents the next great challenge for biomedical science and public health. Fortunately, decades of studies into the biology of aging have provided a head start by revealing an evolutionarily conserved network of genes that controls the rate and quality of the aging process itself and which can thereby be targeted for protection against age-onset disease...
2016: EXS
Zhiyu Wang, Neng Wang, Pengxi Liu, Xiaoming Xie
This chapter focuses on the role of AMPK as a stress-response molecule with an emphasis on its duplex implication in carcinogenesis and cancer drug resistance. AMPK is closely correlated to the tumor-suppressive functions of LKB1 and P53, consequently modulating the activity of cellular survival signaling such as mTOR and Akt, leading to cell growth inhibition and cell cycle arrest. On the contrary, AMPK is tightly involved in cancer drug resistance via interacting with multiple known mechanisms of chemoresistance such as ABCG2 expression, autophagy induction, and cancer stem cells enrichment...
2016: EXS
Evangelos P Daskalopoulos, Cécile Dufeys, Christophe Beauloye, Luc Bertrand, Sandrine Horman
This chapter summarizes the implication of AMP-activated protein kinase (AMPK) in the regulation of various physiological and pathological cellular events of great importance for the maintenance of cardiac function. These include the control of both metabolic and non-metabolic elements targeting the different cellular components of the cardiac tissue, i.e., cardiomyocytes, fibroblasts, and vascular cells. The description of the multifaceted action of the two AMPK catalytic isoforms, α1 and α2, emphasizes the general protective action of this protein kinase against the development of critical pathologies like myocardial ischemia, cardiac hypertrophy, diabetic cardiomyopathy, and heart failure...
2016: EXS
Manon Domise, Valérie Vingtdeux
Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are neurodegenerative disorders that are characterized by a progressive degeneration of nerve cells eventually leading to dementia. While these diseases affect different neuronal populations and present distinct clinical features, they share in common several features and signaling pathways. In particular, energy metabolism defects, oxidative stress, and excitotoxicity are commonly described and might be correlated with AMP-activated protein kinase (AMPK) deregulation...
2016: EXS
Pedro Bullon, Fabiola Marin-Aguilar, Lourdes Roman-Malo
The obtaining of nutrients is the most important task in our lives. Energy is central to life's evolutions; this was one of the aspect that induced the selection of the more adaptable and more energetically profitable species. Nowadays things have changed in our modern society. A high proportion of people has access to plenty amount of food and the obesity appear as one of the pathological characteristics of our society. Energy is obtained essentially in the mitochondria with the transfer of protons across the inner membrane that produce ATP...
2016: EXS
Rasmus Kjøbsted, Jørgen F P Wojtaszewski, Jonas T Treebak
Skeletal muscle insulin resistance precedes development of type 2 diabetes (T2D). As skeletal muscle is a major sink for glucose disposal, understanding the molecular mechanisms involved in maintaining insulin sensitivity of this tissue could potentially benefit millions of people that are diagnosed with insulin resistance. Regular physical activity in both healthy and insulin-resistant individuals is recognized as the single most effective intervention to increase whole-body insulin sensitivity and thereby positively affect glucose homeostasis...
2016: EXS
Melissa R Kaufman, Thomas L Brown
AMPK is important in numerous physiological systems but plays a vital role in embryonic and placental development. The placenta is a unique organ that is the essential lifeline between the mother and baby during pregnancy and gestation. During placental development, oxygen concentrations are very low until cells differentiate to establish the appropriate lineages that take on new functions required for placental and embryonic survival. Balancing the oxygen regulatory environment with the demands for energy and need to maintain metabolism during this process places AMPK at the center of maintaining placental cellular homeostasis as it integrates and responds to numerous complex stimuli...
2016: EXS
Marina Villanueva Paz, David Cotán, Juan Garrido Maraver, Manuel Oropesa-Ávila, Mario de la Mata, Ana Delgado Pavón, Isabel de Lavera, Elizabet Alcocer Gómez, Mónica Álvarez Córdoba, José A Sánchez Alcázar
In eukaryotic cells, AMP-activated protein kinase (AMPK) generally promotes catabolic pathways that produce ATP and at the same time inhibits anabolic pathways involved in different processes that consume ATP. As an energy sensor, AMPK is involved in the main cellular functions implicated in cell fate, such as cell growth and autophagy.Recently, AMPK has been connected with apoptosis regulation, although the molecular mechanism by which AMPK induces and/or inhibits cell death is not clear.This chapter reviews the essential role of AMPK in signaling pathways that respond to cellular stress and damage, highlighting the complex and reciprocal regulation between AMPK and their targets and effectors...
2016: EXS
Yeliz Angin, Christophe Beauloye, Sandrine Horman, Luc Bertrand
This chapter summarizes AMPK function in the regulation of substrate and energy metabolism with the main emphasis on carbohydrate and lipid metabolism, protein turnover, mitochondrial biogenesis, and whole-body energy homeostasis. AMPK acts as whole-body energy sensor and integrates different signaling pathway to meet both cellular and body energy requirements while inhibiting energy-consuming processes but also activating energy-producing ones. AMPK mainly promotes glucose and fatty acid catabolism, whereas it prevents protein, glycogen, and fatty acid synthesis...
2016: EXS
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