scholarly journals Chromatin-associated effectors of energy-sensing pathways mediate intergenerational effects

2020 ◽  
Author(s):  
Pedro Robles ◽  
Anisa Turner ◽  
Giusy Zuco ◽  
Panagiota Paganopolou ◽  
Beth Hill ◽  
...  
Keyword(s):  
Phenotypic Plasticity ◽  
Protein Kinase ◽  
Sex Determination ◽  
Insulin Signaling ◽  
Stress Resistance ◽  
Nutrient Sensing ◽  
Intergenerational Effects ◽  
Mechanistic Target Of Rapamycin ◽  
Energy Sensing ◽  
Amp Activated Protein Kinase

Environmental stimuli experienced by the parental generation influence the phenotype of subsequent generations. The effects of these stimuli on the parental generation may be passed through the germline, but the mechanisms of this non-Mendelian type of inheritance are poorly known. Here we show that modulation of nutrient-sensing pathways in the parental generation of a nematode (Auanema freiburgensis) regulates phenotypic plasticity of its offspring. In response to pheromones, AMP-activated protein kinase (AMPK), mechanistic target of rapamycin complex 1 (mTORC1) and insulin signaling regulate stress resistance and sex determination across a generation. The effectors of these pathways are closely associated with the chromatin and their regulation affects the acetylation chromatin status in the germline. These results suggest that highly conserved metabolic sensors regulate phenotypic plasticity by changing the epigenetic status of the germline.

scholarly journals Parental energy-sensing pathways control intergenerational offspring sex determination in the nematode Auanema freiburgensis

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Pedro Robles ◽  
Anisa Turner ◽  
Giusy Zuco ◽  
Sally Adams ◽  
Panagiota Paganopolou ◽  
...  
Keyword(s):  
Phenotypic Plasticity ◽  
Sex Determination ◽  
Nutrient Sensing ◽  
Transgenerational Inheritance ◽  
Acetylation Status ◽  
Mechanistic Target Of Rapamycin ◽  
Offspring Sex ◽  
Energy Sensing ◽  
Amp Activated Protein Kinase ◽  
Chromatin Acetylation

Abstract Background Environmental stimuli experienced by the parental generation influence the phenotype of subsequent generations (Demoinet et al., Proc Natl Acad Sci U S A 114:E2689-E2698, 2017; Burton et al., Nat Cell Biol 19:252–257, 2017; Agrawal et al., Nature 401:60-63, 1999). The effects of these stimuli on the parental generation may be passed through the germline, but the mechanisms at the basis of this non-Mendelian type of inheritance, their level of conservation, how they lead to adaptive vs non-adaptive, and intergenerational vs transgenerational inheritance are poorly understood. Here we show that modulation of nutrient-sensing pathways in the parental generation of the nematode Auanema freiburgensis regulates phenotypic plasticity of its offspring. Results In response to con-specific pheromones indicative of stress, AMP-activated protein kinase (AMPK), mechanistic target of rapamycin complex 1 (mTORC1), and insulin signaling regulate stress resistance and sex determination across one generation, and these effects can be mimicked by pathway modulators. The effectors of these pathways are closely associated with the chromatin, and their regulation affects the chromatin acetylation status in the germline. Conclusion These results suggest that highly conserved metabolic sensors regulate phenotypic plasticity through regulation of subcellular localization of their effectors, leading to changes in chromatin acetylation and epigenetic status of the germline.

scholarly journals Neuronal AMPK coordinates mitochondrial energy sensing and hypoxia resistance

2020 ◽  
Author(s):  
Brandon J. Berry ◽  
Aksana Baldzizhar ◽  
Andrew P. Wojtovich
Keyword(s):  
Protein Kinase ◽  
Mitochondrial Function ◽  
Stress Resistance ◽  
Atp Synthesis ◽  
Protonmotive Force ◽  
Electrochemical Gradient ◽  
Energy Sensing ◽  
Amp Activated Protein Kinase ◽  
Spatiotemporal Control

ABSTRACTOrganisms adapt to their environment through coordinated changes in mitochondrial function and metabolism. The mitochondrial protonmotive force (PMF) is an electrochemical gradient that powers ATP synthesis and adjusts metabolism to energetic demands via cellular signaling. It is unknown how or where transient PMF changes are sensed and signaled due to lack of precise spatiotemporal control in vivo. We addressed this by expressing a light-activated proton pump in mitochondria to spatiotemporally “turn off” mitochondrial function through PMF dissipation in tissues with light. We applied our construct – mitochondria-OFF (mtOFF) – to understand how metabolic status impacts hypoxia resistance, a response that relies on mitochondrial function. mtOFF activation induced starvation-like behavior mediated by AMP-activated protein kinase (AMPK). We found prophylactic mtOFF activation increased survival following hypoxia, and that protection relied on neuronal AMPK. Our study links spatiotemporal control of mitochondrial PMF to cellular metabolic changes that mediate behavior and stress resistance.

scholarly journals AMP-Activated Protein Kinase (AMPK) and Energy-Sensing in the Brain

2012 ◽  
Vol 21 (2) ◽  
pp. 52-60 ◽  
Author(s):  
Santosh Ramamurthy ◽  
Gabriele Ronnett
Keyword(s):  
Protein Kinase ◽  
Energy Sensing ◽  
Amp Activated Protein Kinase ◽  
The Brain

scholarly journals Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy

Science ◽  
2010 ◽  
Vol 331 (6016) ◽  
pp. 456-461 ◽  
Author(s):  
D. F. Egan ◽  
D. B. Shackelford ◽  
M. M. Mihaylova ◽  
S. Gelino ◽  
R. A. Kohnz ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Energy Sensing ◽  
Amp Activated Protein Kinase

scholarly journals Integration of Nutrient Sensing in Fish Hypothalamus

2021 ◽  
Vol 15 ◽  
Author(s):  
José L. Soengas
Keyword(s):  
Protein Kinase ◽  
Food Intake ◽  
Camp Response Element Binding ◽  
Nutrient Sensing ◽  
Future Research ◽  
Camp Response Element ◽  
Element Binding Protein ◽  
Homeobox Transcription Factor ◽  
Endocrine Signaling ◽  
Amp Activated Protein Kinase

The knowledge regarding hypothalamic integration of metabolic and endocrine signaling resulting in regulation of food intake is scarce in fish. Available studies pointed to a network in which the activation of the nutrient-sensing (glucose, fatty acid, and amino acid) systems would result in AMP-activated protein kinase (AMPK) inhibition and activation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Changes in these signaling pathways would control phosphorylation of transcription factors cAMP response-element binding protein (CREB), forkhead box01 (FoxO1), and brain homeobox transcription factor (BSX) leading to food intake inhibition through changes in the expression of neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opio melanocortin (POMC), and cocaine and amphetamine-related transcript (CART). The present mini-review summarizes information on the topic and identifies gaps for future research.

scholarly journals Antihyperalgesia effect of AMP-activated protein kinase (AMPK) activators in a mouse model of postoperative pain

2019 ◽  
Vol 44 (8) ◽  
pp. 781-786 ◽  
Author(s):  
Vaskar Das ◽  
Jeffrey S Kroin ◽  
Mario Moric ◽  
Robert J McCarthy ◽  
Asokumar Buvanendran
Keyword(s):  
Postoperative Pain ◽  
Protein Kinase ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Drg Neurons ◽  
Mechanical Hypersensitivity ◽  
Mechanistic Target Of Rapamycin ◽  
Initiation Factor 2 ◽  
The Difference ◽  
Amp Activated Protein Kinase

Background and objectivesAMP-activated protein kinase (AMPK) activator drugs decrease hypersensitivity in mice with pain. This study examines if postsurgery treatment with the prototype AMPK activator metformin and a new mechanism-specific AMPK activator, O304, after plantar hindpaw incision in mice, would reduce mechanical hypersensitivity and produce changes in the AMPK pathway in the dorsal root ganglion (DRG).MethodsTo create postoperative pain, an incision was made in the left plantar hindpaw. Animals were randomized into four oral gavage drug treatment groups (n=8/group): (1) vehicle, (2) metformin 200 mg/kg, (3) O304 200 mg/kg and (4) O304 200 mg/kg plus metformin 200 mg/kg. Drug gavages were performed 4 hours postsurgery and were repeated for 3 days. Mechanical hypersensitivity was measured with von Frey filaments. Changes in phosphorylated AMP-activated protein kinase alpha subunit, phosphorylated mechanistic target of rapamycin and phosphorylated eukaryotic initiation factor 2 alpha in DRG neurons were examined by immunohistochemistry.ResultsO304 or metformin increased von Frey thresholds (reduced mechanical hypersensitivity) in plantar incision mice versus vehicle-treated incision mice between days 1 and 4 (difference of mean area under the curve, O304: 2.24 g*day; 95% CI of the difference 0.28 to 4.21, p=0.011; metformin: 2.56 g*day; 95% CI of the difference 1.71 to 3.41, p<0.001). The drug combination further elevated von Frey thresholds. In the vehicle-treated group, the AMP-activated protein kinase alpha subunit was downregulated and mechanistic target of rapamycin and eukaryotic initiation factor 2 alpha were upregulated in DRG neurons; these deficits were reversed by the AMPK activator treatments.ConclusionsEarly treatment with the mechanism-specific AMPK activator O304 or the prototype AMPK activator metformin reduces mechanical hypersensitivity in a postoperative pain model in mice. These drugs also normalize the AMPK pathway in the DRG.

scholarly journals StimulatingS-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK

2016 ◽  
Vol 113 (42) ◽  
pp. 11913-11918 ◽  
Author(s):  
Takafumi Ogawa ◽  
Ryohei Tsubakiyama ◽  
Muneyoshi Kanai ◽  
Tetsuya Koyama ◽  
Tsutomu Fujii ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Cell Survival ◽  
Metabolic Effects ◽  
Model Organisms ◽  
Lifespan Extension ◽  
Beneficial Effects ◽  
Energy Sensing ◽  
Amp Activated Protein Kinase ◽  
Methionine Synthesis

Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met) restriction, extends the lifespan of diverse model organisms. Although studies have identified several metabolites that contribute to the beneficial effects of DR, the molecular mechanism underlying the key metabolites responsible for DR regimens is not fully understood. Here we show that stimulatingS-adenosyl-l-methionine (AdoMet) synthesis extended the lifespan of the budding yeastSaccharomyces cerevisiae. The AdoMet synthesis-mediated beneficial metabolic effects, which resulted from consuming both Met and ATP, mimicked CR. Indeed, stimulating AdoMet synthesis activated the universal energy-sensing regulator Snf1, which is theS. cerevisiaeortholog of AMP-activated protein kinase (AMPK), resulting in lifespan extension. Furthermore, our findings revealed thatS-adenosyl-l-homocysteine contributed to longevity with a higher accumulation of AdoMet only under the severe CR (0.05% glucose) conditions. Thus, our data uncovered molecular links between Met metabolites and lifespan, suggesting a unique function of AdoMet as a reservoir of Met and ATP for cell survival.

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