Novel Nucleolar Pathway Connecting Intracellular Energy Status with p53 Activation

AbstractPathogen recognition and triggering pattern of host innate immune system is critical to understanding pathogen-host interaction. It is generally accepted that the microbial infection can be recognized by host via pattern-triggered immunity (PTI) or effector-triggered immunity (ETI) responses. Recently, non-PRR-mediated cellular surveillance systems have been reported as an important supplement strategy to PTI and ETI responses. However, the mechanism of how surveillance systems sense pathogens and trigger innate immune responses is largely unknown. In the present study, using Bacillus thuringiensis-Caenorhabditis elegans as a model, we found a new approach for surveillance systems to sense the pathogens through no-PPRs patterns. We reported C. elegans can monitor intracellular energy status through the mitochondrial surveillance system to triggered innate immune responses against pathogenic attack via AMP-activated protein kinase (AMPK). Consider that the mitochondria surveillance systems and AMPK are conserved components from worms to mammals, our study suggests that disrupting mitochondrial homeostasis to activate the immune system through AMPK-dependent pathways may widely existing in animals.

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Adenosine and ATP-sensitive potassium channels modulate dopamine release in the anoxic turtle (Trachemys scripta) striatum

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00647.2004 ◽

2005 ◽

Vol 289 (1) ◽

pp. R77-R83 ◽

Cited By ~ 14

Author(s):

Sarah L. Milton ◽

Peter L. Lutz

Keyword(s):

Dopamine Release ◽

Trachemys Scripta ◽

Mammalian Brain ◽

Freshwater Turtle ◽

Energy Status ◽

Gbr 12909 ◽

Butanedione Monoxime ◽

Intracellular Energy

Excessive dopamine (DA) is known to cause hypoxic/ischemic damage to mammalian brain. The freshwater turtle Trachemys scripta, however, maintains basal striatal DA levels in anoxia. We investigated DA balance during early anoxia when energy status in the turtle brain is compromised. The roles of ATP-sensitive potassium (KATP) channels and adenosine (AD) receptors were investigated as these factors affect DA balance in mammalian neurons. Striatal extracellular DA was determined by microdialysis with HPLC in the presence or absence of the specific DA transport blocker GBR-12909, the KATP blocker 2,3-butanedione monoxime, or the nonspecific AD receptor blocker theophylline. We found that in contrast to long-term anoxia, blocking DA reuptake did not significantly increase extracellular levels in 1-h anoxic turtles. Low DA levels in early anoxia were maintained instead by activation of KATP channels and AD receptors. Blocking KATP resulted in a 227% increase in extracellular DA in 1-h anoxic turtles but had no effect after 4 h of anoxia. Similarly, blocking AD receptors increased DA during the first hour of anoxia but did not change DA levels at 4-h anoxia. Support for the role of KATP channels in DA balance comes from normoxic animals treated with KATP opener; infusing diazoxide but not adenosine into the normoxic turtle striatum resulted in an immediate DA decrease to 14% of basal values within 1.5 h. Alternative strategies to maintain low extracellular levels may prevent catastrophic DA increases when intracellular energy is compromised while permitting the turtle to maintain a functional neuronal network during long-term anoxia.

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Interference with energy metabolism by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside induces HPV suppression in cervical carcinoma cells and apoptosis in the absence of LKB11

Biochemical Journal ◽

10.1042/bj20061053 ◽

2007 ◽

Vol 403 (3) ◽

pp. 501-510 ◽

Cited By ~ 15

Author(s):

Julia Nafz ◽

Johanna De-Castro Arce ◽

Verena Fleig ◽

Andrea Patzelt ◽

Sybille Mazurek ◽

...

Keyword(s):

Cervical Carcinoma ◽

Metabolic Stress ◽

Carcinoma Cells ◽

Activator Protein 1 ◽

Energy Status ◽

Hypoxic Conditions ◽

Upstream Kinase ◽

P53 Activation ◽

Amp Activated Protein Kinase ◽

Interfering Rna

Carcinogenesis is a dynamic and stepwise process, which is accompanied by a variety of somatic and epigenetic alterations in response to a changing microenvironment. Hypoxic conditions will select for cells that have adjusted their metabolic profile and can maintain proliferation by successfully competing for scarce nutritional and oxygen resources. In the present study we have investigated the effects of energy depletion in the context of HPV (human papillomavirus)-induced pathogenesis. We show that cervical carcinoma cell lines are susceptible to undergoing either growth arrest or cell death under conditions of metabolic stress induced by AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside), a known activator of the AMPK (AMP-activated protein kinase). Our results reveal that AICAR treatment leads to a reduced binding affinity of the transcription factor AP-1 (activator protein-1) and in turn to a selective suppression of HPV transcription. Moreover, the outcome of AICAR on proliferation and survival was dependent on p53 activation and the presence of LKB1, the major upstream kinase of AMPK. Using non-malignant LKB1-expressing somatic cell hybrids, which lose expression after tumorigenic segregation, as well as small interfering RNA LKB1 knockdown approaches, we could further demonstrate that expression of LKB1 protects cells from cytotoxicity induced by agents which modulate the ATP/AMP ratio. Since simulation of low energy status can selectively eradicate LKB1-negative cervical carcinoma cells, AICAR may represent a novel drug in the treatment of cervical cancer.

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Coupling metabolism and chemotaxis-dependent behaviours by energy taxis receptors

Microbiology ◽

10.1099/mic.0.039214-0 ◽

2010 ◽

Vol 156 (8) ◽

pp. 2283-2293 ◽

Cited By ~ 58

Author(s):

Gladys Alexandre

Keyword(s):

Bacterial Species ◽

Energy Status ◽

Chemical Parameters ◽

Directed Movement ◽

Energy Taxis ◽

Physico Chemical ◽

Dependent Form ◽

Energy Sensing ◽

Metabolic Activities ◽

Intracellular Energy

Bacteria have evolved the ability to monitor changes in various physico-chemical parameters and to adapt their physiology and metabolism by implementing appropriate cellular responses to these changes. Energy taxis is a metabolism-dependent form of taxis and is the directed movement of motile bacteria in gradients of physico-chemical parameters that affect metabolism. Energy taxis has been described in diverse bacterial species and several dedicated energy sensors have been identified. The molecular mechanism of energy taxis has not been studied in as much detail as chemotaxis, but experimental evidence indicates that this behaviour differs from metabolism-independent taxis only by the presence of dedicated energy taxis receptors. Energy taxis receptors perceive changes in energy-related parameters, including signals related to the redox and/or intracellular energy status of the cell. The best-characterized energy taxis receptors are those that sense the redox state of the electron transport chain via non-covalently bound FAD cofactors. Other receptors shown to mediate energy taxis lack any recognizable redox cofactor or conserved energy-sensing motif, and some have been suggested to monitor changes in the proton motive force. The exact energy-sensing mechanism(s) involved are yet to be elucidated for most of these energy sensors. By monitoring changes in energy-related parameters, energy taxis receptors allow cells to couple motility behaviour with metabolism under diverse environmental conditions. Energy taxis receptors thus provide fruitful models to decipher how cells integrate sensory behaviours with metabolic activities.

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Synphilin-1 Binds ATP and Regulates Intracellular Energy Status

PLoS ONE ◽

10.1371/journal.pone.0115233 ◽

2014 ◽

Vol 9 (12) ◽

pp. e115233 ◽

Cited By ~ 4

Author(s):

Tianxia Li ◽

Jingnan Liu ◽

Wanli W. Smith

Keyword(s):

Energy Status ◽

Intracellular Energy

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Relieving Cellular Energy Stress in Aging, Neurodegenerative, and Metabolic Diseases, SIRT1 as a Therapeutic and Promising Node

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.738686 ◽

2021 ◽

Vol 13 ◽

Author(s):

Yang Fang ◽

Xifeng Wang ◽

Danying Yang ◽

Yimei Lu ◽

Gen Wei ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Metabolic Diseases ◽

Energy State ◽

Energy Status ◽

Atp Production ◽

Energy Stress ◽

Silent Information Regulator 1 ◽

The Stability ◽

Intracellular Energy ◽

Expression And Activity

The intracellular energy state will alter under the influence of physiological or pathological stimuli. In response to this change, cells usually mobilize various molecules and their mechanisms to promote the stability of the intracellular energy status. Mitochondria are the main source of ATP. Previous studies have found that the function of mitochondria is impaired in aging, neurodegenerative diseases, and metabolic diseases, and the damaged mitochondria bring lower ATP production, which further worsens the progression of the disease. Silent information regulator-1 (SIRT1) is a multipotent molecule that participates in the regulation of important biological processes in cells, including cellular metabolism, cell senescence, and inflammation. In this review, we mainly discuss that promoting the expression and activity of SIRT1 contributes to alleviating the energy stress produced by physiological and pathological conditions. The review also discusses the mechanism of precise regulation of SIRT1 expression and activity in various dimensions. Finally, according to the characteristics of this mechanism in promoting the recovery of mitochondrial function, the relationship between current pharmacological preparations and aging, neurodegenerative diseases, metabolic diseases, and other diseases was analyzed.

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Epigenetic Control of rDNA Loci in Response to Intracellular Energy Status

Cell ◽

10.1016/j.cell.2008.03.030 ◽

2008 ◽

Vol 133 (4) ◽

pp. 627-639 ◽

Cited By ~ 263

Author(s):

Akiko Murayama ◽

Kazuji Ohmori ◽

Akiko Fujimura ◽

Hiroshi Minami ◽

Kayoko Yasuzawa-Tanaka ◽

...

Keyword(s):

Energy Status ◽

Epigenetic Control ◽

Rdna Loci ◽

Intracellular Energy

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Energetic limits to metabolic flexibility: responses of Saccharomyces cerevisiae to glucose–galactose transitions

Microbiology ◽

10.1099/mic.0.025775-0 ◽

2009 ◽

Vol 155 (4) ◽

pp. 1340-1350 ◽

Cited By ~ 33

Author(s):

J. van den Brink ◽

M. Akeroyd ◽

R. van der Hoeven ◽

J. T. Pronk ◽

J. H. de Winde ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Energy Charge ◽

Metabolic Flexibility ◽

Energy Status ◽

Anaerobic Conditions ◽

Leloir Pathway ◽

Chemostat Cultures ◽

Galactose Utilization ◽

Intracellular Energy ◽

Adenosine Nucleotide

Glucose is the favoured carbon source for Saccharomyces cerevisiae, and the Leloir pathway for galactose utilization is only induced in the presence of galactose during glucose-derepressed conditions. The goal of this study was to investigate the dynamics of glucose–galactose transitions. To this end, well-controlled, glucose-limited chemostat cultures were switched to galactose-excess conditions. Surprisingly, galactose was not consumed upon a switch to galactose excess under anaerobic conditions. However, the transcripts of the Leloir pathway were highly increased upon galactose excess under both aerobic and anaerobic conditions. Protein and enzyme-activity assays showed that impaired galactose consumption under anaerobiosis coincided with the absence of the Leloir-pathway proteins. Further results showed that absence of protein synthesis was not caused by glucose-mediated translation inhibition. Analysis of adenosine nucleotide pools revealed a fast decrease of the energy charge after the switch from glucose to galactose under anaerobic conditions. Similar results were obtained when glucose–galactose transitions were analysed under aerobic conditions with a respiratory-deficient strain. It is concluded that under fermentative conditions, the energy charge was too low to allow synthesis of the Leloir proteins. Hence, this study conclusively shows that the intracellular energy status is an important factor in the metabolic flexibility of S. cerevisiae upon changes in its environment.

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Intracellular energy status regulates activity in hypocretin/orexin neurones: a link between energy and behavioural states

The Journal of Physiology ◽

10.1113/jphysiol.2011.212514 ◽

2011 ◽

Vol 589 (17) ◽

pp. 4157-4166 ◽

Cited By ~ 29

Author(s):

Zhong-Wu Liu ◽

Geliang Gan ◽

Shigetomo Suyama ◽

Xiao-Bing Gao

Keyword(s):

Energy Status ◽

Intracellular Energy

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