AMPK mediates energetic stress‐induced liver GDF15

In Streptomyces, antibiotic biosynthesis is triggered in phosphate limitation that is usually correlated with energetic stress. Polyphosphates constitute an important reservoir of phosphate and energy and a better understanding of their role in the regulation of antibiotic biosynthesis is of crucial importance. We previously characterized a gene, SLI_4384/ppk, encoding a polyphosphate kinase, whose disruption greatly enhanced the weak antibiotic production of Streptomyces lividans. In the condition of energetic stress, Ppk utilizes polyP as phosphate and energy donor, to generate ATP from ADP. In this paper, we established that ppk is co-transcribed with its two downstream genes, SLI_4383, encoding a phosin called PptA possessing a CHAD domain constituting a polyphosphate binding module and SLI_4382 encoding a nudix hydrolase. The expression of the ppk/pptA/SLI_4382 operon was shown to be under the positive control of the two-component system PhoR/PhoP and thus mainly expressed in condition of phosphate limitation. However, pptA and SLI_4382 can also be transcribed alone from their own promoter. The deletion of pptA resulted into earlier and stronger actinorhodin production and lower lipid content than the disruption of ppk, whereas the deletion of SLI_4382 had no obvious phenotypical consequences. The disruption of ppk was shown to have a polar effect on the expression of pptA, suggesting that the phenotype of the ppk mutant might be linked, at least in part, to the weak expression of pptA in this strain. Interestingly, the expression of phoR/phoP and that of the genes of the pho regulon involved in phosphate supply or saving were strongly up-regulated in pptA and ppk mutants, revealing that both mutants suffer from phosphate stress. Considering the presence of a polyphosphate binding module in PptA, but absence of similarities between PptA and known exo-polyphosphatases, we proposed that PptA constitutes an accessory factor for exopolyphosphatases or general phosphatases involved in the degradation of polyphosphates into phosphate.

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LKB1 and AMPK maintain epithelial cell polarity under energetic stress

The Journal of Cell Biology ◽

10.1083/jcb.200702053 ◽

2007 ◽

Vol 177 (3) ◽

pp. 387-392 ◽

Cited By ~ 134

Author(s):

Vincent Mirouse ◽

Lance L. Swick ◽

Nevzat Kazgan ◽

Daniel St Johnston ◽

Jay E. Brenman

Keyword(s):

Tumor Suppressor ◽

Cell Polarity ◽

Growth Control ◽

Epithelial Polarity ◽

Energy Status ◽

Ampk Signaling ◽

Cellular Energy ◽

Energetic Stress ◽

Stress Dependent

LKB1 is mutated in both familial and spontaneous tumors, and acts as a master kinase that activates the PAR-1 polarity kinase and the adenosine 5′monophosphate–activated kinase (AMPK). This has led to the hypothesis that LKB1 acts as a tumor suppressor because it is required to maintain cell polarity and growth control through PAR-1 and AMPK, respectively. However, the genetic analysis of LKB1–AMPK signaling in vertebrates has been complicated by the existence of multiple redundant AMPK subunits. We describe the identification of mutations in the single Drosophila melanogaster AMPK catalytic subunit AMPKα. Surprisingly, ampkα mutant epithelial cells lose their polarity and overproliferate under energetic stress. LKB1 is required in vivo for AMPK activation, and lkb1 mutations cause similar energetic stress–dependent phenotypes to ampkα mutations. Furthermore, lkb1 phenotypes are rescued by a phosphomimetic version of AMPKα. Thus, LKB1 signals through AMPK to coordinate epithelial polarity and proliferation with cellular energy status, and this might underlie the tumor suppressor function of LKB1.

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Dynamic response in the larval geoduck clam proteome to elevated pCO2

10.1101/613018 ◽

2019 ◽

Author(s):

Emma Timmins-Schiffman ◽

José M. Guzmán ◽

Rhonda Elliott ◽

Brent Vadopalas ◽

Steven B. Roberts

Keyword(s):

Ocean Acidification ◽

Pacific Coast ◽

Low Ph ◽

Molecular Physiology ◽

Proteomics Analysis ◽

Bivalve Larvae ◽

Energetic Stress ◽

The Pacific ◽

Aquaculture Industry ◽

Ph Conditions

AbstractPacific geoduck clams (Panopea generosa) are found along the Northeast Pacific coast where they are significant components of coastal and estuarine ecosystems and the basis of a growing and highly profitable aquaculture industry. The Pacific coastline, however, is also the sight of rapidly changing ocean habitat, including significant reductions in pH. The impacts of ocean acidification on invertebrate bivalve larvae have been widely documented and it is well established that many species experience growth and developmental deficiencies when exposed to low pH. As a native of environments that have historically lower pH than the open ocean, it is possible that geoduck larvae are less impacted by these effects than other species. Over two weeks in larval development (days 6-19 post-fertilization) geoduck larvae were reared at pH 7.5 or 7.1 in a commercial shellfish hatchery. Larvae were sampled at six time points throughout the period for a in-depth proteomics analysis of developmental molecular physiology. Larvae reared at low pH were smaller than those reared at ambient pH, especially in the prodissoconch II phase of development. Competency for settlement was also delayed in larvae from the low pH conditions. A comparison of proteomic profiles over the course of development reveal that these differing phenotypic outcomes are likely due to environmental disruptions to the timing of molecular physiological events as suites of proteins showed differing profiles of abundance between the two pH environments. Ocean acidification likely caused an energetic stress on the larvae at pH 7.1, causing a shift in physiological prioritization with resulting loss of fitness.

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Structural basis for SARM1 inhibition and activation under energetic stress

eLife ◽

10.7554/elife.62021 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Michael Sporny ◽

Julia Guez-Haddad ◽

Tami Khazma ◽

Avraham Yaron ◽

Moshe Dessau ◽

...

Keyword(s):

Cell Death ◽

Axonal Degeneration ◽

Structural Basis ◽

Allosteric Site ◽

Inactive Conformation ◽

Catalytic Domains ◽

Energetic Stress ◽

Catalytic Sites ◽

Peripheral Ring ◽

Cellular Metabolite

SARM1, an executor of axonal degeneration, displays NADase activity that depletes the key cellular metabolite, NAD+, in response to nerve injury. The basis of SARM1 inhibition and its activation under stress conditions are still unknown. Here, we present cryo-EM maps of SARM1 at 2.9 and 2.7 Å resolutions. These indicate that SARM1 homo-octamer avoids premature activation by assuming a packed conformation, with ordered inner and peripheral rings, that prevents dimerization and activation of the catalytic domains. This inactive conformation is stabilized by binding of SARM1’s own substrate NAD+ in an allosteric location, away from the catalytic sites. This model was validated by mutagenesis of the allosteric site, which led to constitutively active SARM1. We propose that the reduction of cellular NAD+ concentration contributes to the disassembly of SARM1's peripheral ring, which allows formation of active NADase domain dimers, thereby further depleting NAD+ to cause an energetic catastrophe and cell death.

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Skeletal and Dental Development Preserve Evidence of Energetic Stress in the Moose of Isle Royale

Frontiers in Ecology and Evolution ◽

10.3389/fevo.2020.00272 ◽

2020 ◽

Vol 8 ◽

Author(s):

Caitlin Brown ◽

Caroline E. Rinaldi ◽

William J. Ripple ◽

Blaire Van Valkenburgh

Keyword(s):

Dental Development ◽

Isle Royale ◽

Energetic Stress ◽

Skeletal And Dental Development

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Inhibition of Hepatic Phosphatidylcholine Synthesis by 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside Is Independent of AMP-activated Protein Kinase Activation

Journal of Biological Chemistry ◽

10.1074/jbc.m605702200 ◽

2006 ◽

Vol 282 (7) ◽

pp. 4516-4523 ◽

Cited By ~ 42

Author(s):

René L. Jacobs ◽

Susanne Lingrell ◽

Jason R. B. Dyck ◽

Dennis E. Vance

Keyword(s):

Protein Kinase ◽

Mammalian Cells ◽

Isolated Hepatocytes ◽

Dominant Negative ◽

Kinase Activation ◽

Energetic Stress ◽

Adenoviral Delivery ◽

Protein Kinase Activation ◽

Dependent Inhibition ◽

Amp Activated Protein Kinase

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAr), a commonly used indirect activator of AMP-activated protein kinase (AMPK), inhibits phosphatidylcholine (PC) biosynthesis in freshly isolated hepatocytes. In all nucleated mammalian cells, PC is synthesized from choline via the Kennedy (CDP-choline) pathway. The purpose of our study was to provide direct evidence that AMPK regulates phospholipid biosynthesis and to elucidate the mechanism(s) by which AMPK inhibits hepatic PC synthesis. Incubations of hepatocytes with AICAr resulted in a dose-dependent activation of AMPK and inhibition of PC biosynthesis. Surprisingly, adenoviral delivery of constitutively active AMPK did not alter PC biosynthesis. In addition, expression of dominant negative mutants of AMPK was unable to block the AICAr-dependent inhibition of PC biosynthesis, indicating that AICAr was acting independently of AMPK activation. Determination of aqueous intermediates of the CDP-choline pathway indicated that choline kinase, the first enzyme in the pathway, was inhibited by AICAr administration. Flux through the CDP-choline pathway was directly correlated to the level of intracellular ATP concentrations. Therefore, it is possible that inhibition of PC biosynthesis is another process by which the cell can reduce ATP consumption in times of energetic stress. However, unlike cholesterol and triacylglycerol biosynthesis, PC production is not regulated by AMPK.

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Parental care in the common eider (Somateria mollissima): factors affecting abandonment and adoption of young

Canadian Journal of Zoology ◽

10.1139/z91-216 ◽

1991 ◽

Vol 69 (6) ◽

pp. 1538-1545 ◽

Cited By ~ 64

Author(s):

Jan O. Bustnes ◽

Kjell E. Erikstad

Keyword(s):

Parental Care ◽

Somateria Mollissima ◽

Factors Affecting ◽

Lower Survival Rate ◽

Duckling Survival ◽

Energetic Stress ◽

Lower Body Weight ◽

Common Eiders ◽

The Common ◽

Individual Strategies

Parental care in common eiders (Somateria mollissima) was studied during three field seasons in northern Norway. Forty-two percent of the females were found to abandon their brood. Abandonment and tending of broods and crèches were not obligate individual strategies, but changed between years. Females abandoning their young laid smaller clutches and had a lower body weight at hatching than brood- and crèche-tending females, indicating that they were in poor body condition. This supports the hypothesis that abandoning the brood is a salvage strategy in which energetic stress limits females' ability to care for their young. Young of "abandoners" seemed to have a lower survival rate than young of "tenders," which suggests a reproductive cost of abandoning the young. Forty-seven percent of tagged ducklings were found with females other than their mother. Twenty-seven percent of the brood- and crèche-tending females lost young to other females, but never more than one duckling. Adoptions of foreign ducklings, above the normal brood size of four, did not lead to greater parental effort, and duckling survival was similar among broods and crèches of different sizes. This suggests that adoptions may be of neutral adaptive value. Two females often formed stable crèches, but duckling survival was not significantly different from that in broods and crèches with single females.

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Energy expenditure of Gambian women during peak agricultural activity measured by the doubly-labelled water method

British Journal Of Nutrition ◽

10.1079/bjn19890033 ◽

1989 ◽

Vol 62 (2) ◽

pp. 315-329 ◽

Cited By ~ 122

Author(s):

J. Singh ◽

A. M. Prentice ◽

E. Diaz ◽

W.A. Coward ◽

J. Ashford ◽

...

Keyword(s):

Energy Expenditure ◽

Resting Metabolic Rate ◽

Negative Energy ◽

Total Energy Expenditure ◽

Agricultural Activity ◽

Weight Changes ◽

Free Living ◽

Doubly Labelled Water ◽

Agricultural Work ◽

Energetic Stress

The doubly-labelled water (2H218O) method was used to measure total energy expenditure (TEE) in ten non-pregnant, non-lactating (NPNL), six pregnant (P) and fourteen lactating (L) women in a rural Gambian community. Measurements were made on free-living subjects at a period of peak energetic stress when high agricultural work loads coincided with a hungry season to induce moderately severe negative energy balance. TEE averaged 10.42 (SD 2.08) MJ/d, equivalent to 1.95 (SD 0.38) times resting metabolic rate (RMR). The energy cost of physical activity plus thermogenesis, derived as TEE – RMR, averaged 4.94 (SD 1.96) MJ/d. Expressed per kg body-weight (103 kJ/kg per d) this component of expenditure was 2.5 times greater than comparative values from inactive, affluent women studied previously (39 kJ/kg per d). Estimated energy intake (EI) in a subset of the women (n 13) was only 4.80 (SD 1.58) MJ/d, yielding an apparent deficit of 6.08 MJ/d between EI and TEE. Weight changes suggested that endogenous fat oxidation accounted for only about 0.85 MJ/d, leaving an unexplained difference of over 5 MJ/d. Critical analysis of possible errors suggests that the new doubly-labelled water method has provided the most reliable estimates and that the estimates of EI were substantially in error. This finding has important consequences for other food intake studies.

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Nosema spp. infections cause no energetic stress in tolerant honeybees

Parasitology Research ◽

10.1007/s00436-016-4988-3 ◽

2016 ◽

Vol 115 (6) ◽

pp. 2381-2388 ◽

Cited By ~ 20

Author(s):

Christoph Kurze ◽

Christopher Mayack ◽

Frank Hirche ◽

Gabriele I. Stangl ◽

Yves Le Conte ◽

...

Keyword(s):

Energetic Stress

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