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https://www.readbyqxmd.com/read/29045932/modulation-of-sestrin-confers-protection-to-cr-vi-induced-neuronal-cell-death-in-drosophila-melanogaster
#1
Pallavi Singh, D Kar Chowdhuri
Increased oxidative stress is one of the major causes of hexavalent chromium [Cr(VI)], a heavy metal with diverse applications and environmental presence, induced neuronal adversities in exposed organism including Drosophila. Sestrin (sesn), an oxidative stress responsive gene, emerges as a novel player in the management of oxidative stress response. It is reported to be regulated by Target of rapamycin (TOR) and the former regulates autophagy and plays an important role in the prevention of neurodegeneration...
October 7, 2017: Chemosphere
https://www.readbyqxmd.com/read/28971552/tor-mediated-regulation-of-metabolism-in-aging
#2
REVIEW
Henri Antikainen, Monica Driscoll, Gal Haspel, Radek Dobrowolski
Cellular metabolism is regulated by the mTOR kinase, a key component of the molecular nutrient sensor pathway that plays a central role in cellular survival and aging. The mTOR pathway promotes protein and lipid synthesis and inhibits autophagy, a process known for its contribution to longevity in several model organisms. The nutrient-sensing pathway is regulated at the lysosomal membrane by a number of proteins for which deficiency triggers widespread aging phenotypes in tested animal models. In response to environmental cues, this recently discovered lysosomal nutrient-sensing complex regulates autophagy transcriptionally through conserved factors, such as the transcription factors TFEB and FOXO, associated with lifespan extension...
October 2, 2017: Aging Cell
https://www.readbyqxmd.com/read/28949794/control-of-protein-translation-by-ip3r-mediated-ca-2-release-in-drosophila-neuroendocrine-cells
#3
Gaiti Hasan
The inositol 1,4,5-trisphosphate receptor (IP3R) is one of two Ca(2+) channels that gates Ca(2+) release from ER-stores. The ligand IP3, generated upon specific G-protein coupled receptor activation, binds to IP3R to release Ca(2+) into the cytosol. IP3R also mediates ER-store Ca(2+) release into the mitochondria, under basal as well as stimulatory conditions; an activity that influences cellular bioenergetics and thus, cellular growth and proliferation. In Drosophila neuroendocrine cells expressing a hypomorphic mutant of IP3R, we observed reduced protein translation levels...
September 26, 2017: Fly
https://www.readbyqxmd.com/read/28941010/atad3-proteins-brokers-of-a-mitochondria-endoplasmic-reticulum-connection-in-mammalian-cells
#4
Jacques Baudier
In yeast, a sequence of physical and genetic interactions termed the endoplasmic reticulum (ER)-mitochondria organizing network (ERMIONE) controls mitochondria-ER interactions and mitochondrial biogenesis. Several functions that characterize ERMIONE complexes are conserved in mammalian cells, suggesting that a similar tethering complex must exist in metazoans. Recent studies have identified a new family of nuclear-encoded ATPases associated with diverse cellular activities (AAA+-ATPase) mitochondrial membrane proteins specific to multicellular eukaryotes, called the ATPase family AAA domain-containing protein 3 (ATAD3) proteins (ATAD3A and ATAD3B)...
September 20, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28925355/loss-of-foxo-rescues-stem-cell-aging-in-drosophila-germ-line
#5
Filippo Artoni, Rebecca E Kreipke, Ondina Palmeira, Connor Dixon, Zachary Goldberg, Hannele Ruohola-Baker
Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28893568/endocrine-and-physiological-regulation-of-neutral-fat-storage-in-drosophila
#6
REVIEW
Michael Lehmann
After having revolutionized our understanding of the mechanisms of animal development, Drosophila melanogaster has more recently emerged as an equally valid genetic model in the field of animal metabolism. An increasing number of studies have revealed that many signaling pathways that control metabolism in mammals, including pathways controlled by nutrients (insulin, TOR), steroid hormone, glucagon, and hedgehog, are functionally conserved between mammals and Drosophila. In fact, genetic screens and analyses in Drosophila have identified new players and filled in gaps in the signaling networks that control metabolism...
September 8, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28700947/acute-dietary-restriction-acts-via-tor-pp2a-and-myc-signaling-to-boost-innate-immunity-in-drosophila
#7
Jung-Eun Lee, Morsi Rayyan, Allison Liao, Isaac Edery, Scott D Pletcher
Dietary restriction promotes health and longevity across taxa through mechanisms that are largely unknown. Here, we show that acute yeast restriction significantly improves the ability of adult female Drosophila melanogaster to resist pathogenic bacterial infections through an immune pathway involving downregulation of target of rapamycin (TOR) signaling, which stabilizes the transcription factor Myc by increasing the steady-state level of its phosphorylated forms through decreased activity of protein phosphatase 2A...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28592498/genetic-dissection-of-nutrition-induced-plasticity-in-insulin-insulin-like-growth-factor-signaling-and-median-life-span-in-a-drosophila-multiparent-population
#8
Patrick D Stanley, Enoch Ng'oma, Siri O'Day, Elizabeth G King
The nutritional environments that organisms experience are inherently variable, requiring tight coordination of how resources are allocated to different functions relative to the total amount of resources available. A growing body of evidence supports the hypothesis that key endocrine pathways play a fundamental role in this coordination. In particular, the insulin/insulin-like growth factor signaling (IIS) and target of rapamycin (TOR) pathways have been implicated in nutrition-dependent changes in metabolism and nutrient allocation...
June 2017: Genetics
https://www.readbyqxmd.com/read/28485389/egfr-dependent-tor-independent-endocycles-support-drosophila-gut-epithelial-regeneration
#9
Jinyi Xiang, Jennifer Bandura, Peng Zhang, Yinhua Jin, Hanna Reuter, Bruce A Edgar
Following gut epithelial damage, epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signalling triggers Drosophila intestinal stem cells to produce enteroblasts (EBs) and enterocytes (ECs) that regenerate the gut. As EBs differentiate into ECs, they become postmitotic, but undergo extensive growth and DNA endoreplication. Here we report that EGFR/RAS/MAPK signalling is required and sufficient to drive damage-induced EB/EC growth. Endoreplication occurs exclusively in EBs and newborn ECs that inherit EGFR and active MAPK from fast-dividing progenitors...
May 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28406902/bicaudal-c-mutation-causes-myc-and-tor-pathway-up-regulation-and-polycystic-kidney-disease-like-phenotypes-in-drosophila
#10
Chiara Gamberi, David R Hipfner, Marie Trudel, William D Lubell
Progressive cystic kidney degeneration underlies diverse renal diseases, including the most common cause of kidney failure, autosomal dominant Polycystic Kidney Disease (PKD). Genetic analyses of patients and animal models have identified several key drivers of this disease. The precise molecular and cellular changes underlying cystogenesis remain, however, elusive. Drosophila mutants lacking the translational regulator Bicaudal C (BicC, the fly ortholog of vertebrate BICC1 implicated in renal cystogenesis) exhibited progressive cystic degeneration of the renal tubules (so called "Malpighian" tubules) and reduced renal function...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28363744/dref-plays-multiple-roles-during-drosophila-development
#11
REVIEW
Nguyen Trong Tue, Yasuhide Yoshioka, Megumi Mizoguchi, Hideki Yoshida, Mario Zurita, Masamitsu Yamaguchi
DREF was originally identified as a transcription factor that coordinately regulates the expression of DNA replication- and proliferation-related genes in Drosophila. Subsequent studies demonstrated that DREF is involved in tumor suppressor pathways including p53 and Hippo signaling. DREF also regulates the expression of genes encoding components of the JNK and EGFR pathways during Drosophila development. DREF itself is under the control of the TOR pathway during cell and tissue growth responding to nutrition...
June 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28317899/minocycline-treatment-suppresses-juvenile-development-and-growth-by-attenuating-insulin-tor-signaling-in-drosophila-animal-model
#12
Hyun Myoung Yun, Sujin Noh, Seogang Hyun
Minocycline is a broad spectrum, semi-synthetic tetracycline analog that is used to treat bacterial infection. Recently, this drug has been receiving increasing attention for its non-antibiotic properties, including anti-inflammatory, tumor suppressive, and neuroprotective effects. Drosophila is a useful model organism for studying human metabolism and disease. In this study, we investigated the effects of minocycline on juvenile development and growth in Drosophila. Feeding minocycline to Drosophila larvae suppresses larval body growth and delays the timing of pupation in a dose-dependent manner...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28241077/%C3%AE-amanitin-resistance-in-drosophila-melanogaster-a-genome-wide-association-approach
#13
Chelsea L Mitchell, Catrina E Latuszek, Kara R Vogel, Ian M Greenlund, Rebecca E Hobmeier, Olivia K Ingram, Shannon R Dufek, Jared L Pecore, Felicia R Nip, Zachary J Johnson, Xiaohui Ji, Hairong Wei, Oliver Gailing, Thomas Werner
We investigated the mechanisms of mushroom toxin resistance in the Drosophila Genetic Reference Panel (DGRP) fly lines, using genome-wide association studies (GWAS). While Drosophila melanogaster avoids mushrooms in nature, some lines are surprisingly resistant to α-amanitin-a toxin found solely in mushrooms. This resistance may represent a pre-adaptation, which might enable this species to invade the mushroom niche in the future. Although our previous microarray study had strongly suggested that pesticide-metabolizing detoxification genes confer α-amanitin resistance in a Taiwanese D...
2017: PloS One
https://www.readbyqxmd.com/read/28196106/tor-signaling-pathway-and-autophagy-are-involved-in-the-regulation-of-circadian-rhythms-in-behavior-and-plasticity-of-l2-interneurons-in-the-brain-of-drosophila-melanogaster
#14
Ewelina Kijak, Elżbieta Pyza
Drosophila melanogaster is a common model used to study circadian rhythms in behavior and circadian clocks. However, numerous circadian rhythms have also been detected in non-clock neurons, especially in the first optic neuropil (lamina) of the fly's visual system. Such rhythms have been observed in the number of synapses and in the structure of interneurons, which exhibit changes in size and shape in a circadian manner. Although the patterns of these changes are known, the mechanism remains unclear. In the present study, we investigated the role of the TOR signaling pathway and autophagy in regulating circadian rhythms based on the behavior and structural plasticity of the lamina L2 monopolar cell dendritic trees...
2017: PloS One
https://www.readbyqxmd.com/read/28121986/nutrient-dependent-endocycling-in-steroidogenic-tissue-dictates-timing-of-metamorphosis-in-drosophila-melanogaster
#15
Yuya Ohhara, Satoru Kobayashi, Naoki Yamanaka
Many animals have an intrinsic growth checkpoint during juvenile development, after which an irreversible decision is made to upregulate steroidogenesis, triggering the metamorphic juvenile-to-adult transition. However, a molecular process underlying such a critical developmental decision remains obscure. Here we show that nutrient-dependent endocycling in steroidogenic cells provides the machinery necessary for irreversible activation of metamorphosis in Drosophila melanogaster. Endocycle progression in cells of the prothoracic gland (PG) is tightly coupled with the growth checkpoint, and block of endocycle in PG cells causes larval developmental arrest due to reduction in biosynthesis of the steroid hormone ecdysone...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28077876/microenvironmental-autophagy-promotes-tumour-growth
#16
Nadja S Katheder, Rojyar Khezri, Fergal O'Farrell, Sebastian W Schultz, Ashish Jain, Mohammed M Rahman, Kay O Schink, Theodossis A Theodossiou, Terje Johansen, Gábor Juhász, David Bilder, Andreas Brech, Harald Stenmark, Tor Erik Rusten
As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues. Tumour growth can be pharmacologically restrained using autophagy inhibitors, and early-stage tumour growth and invasion are genetically dependent on autophagy within the local tumour microenvironment...
January 19, 2017: Nature
https://www.readbyqxmd.com/read/27916456/acute-fasting-regulates-retrograde-synaptic-enhancement-through-a-4e-bp-dependent-mechanism
#17
Grant Kauwe, Kazuya Tsurudome, Jay Penney, Megumi Mori, Lindsay Gray, Mario R Calderon, Fatima Elazouzzi, Nicole Chicoine, Nahum Sonenberg, A Pejmun Haghighi
While beneficial effects of fasting on organismal function and health are well appreciated, we know little about the molecular details of how fasting influences synaptic function and plasticity. Our genetic and electrophysiological experiments demonstrate that acute fasting blocks retrograde synaptic enhancement that is normally triggered as a result of reduction in postsynaptic receptor function at the Drosophila larval neuromuscular junction (NMJ). This negative regulation critically depends on transcriptional enhancement of eukaryotic initiation factor 4E binding protein (4E-BP) under the control of the transcription factor Forkhead box O (Foxo)...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/27909242/beneficial-effects-of-rapamycin-in-a-drosophila-model-for-hereditary-spastic-paraplegia
#18
Shiyu Xu, Michael Stern, James A McNew
The locomotor deficits in the group of diseases referred to as hereditary spastic paraplegia (HSP) reflect degeneration of upper motor neurons, but the mechanisms underlying this neurodegeneration are unknown. We established a Drosophila model for HSP, atlastin (atl), which encodes an ER fusion protein. Here, we show that neuronal atl loss causes degeneration of specific thoracic muscles that is preceded by other pathologies, including accumulation of aggregates containing polyubiquitin, increased generation of reactive oxygen species and activation of the JNK-Foxo stress response pathway...
January 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/27904993/molecular-mechanisms-of-heart-failure-insights-from-drosophila
#19
Shasha Zhu, Zhe Han, Yan Luo, Yulin Chen, Qun Zeng, Xiushan Wu, Wuzhou Yuan
Heart failure places an enormous burden on health and economic systems worldwide. It is a complex disease that is profoundly influenced by both genetic and environmental factors. Neither the molecular mechanisms underlying heart failure nor effective prevention strategies are fully understood. Fortunately, relevant aspects of human heart failure can be experimentally studied in tractable model animals, including the fruit fly, Drosophila, allowing the in vivo application of powerful and sophisticated molecular genetic and physiological approaches...
January 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/27741510/rapamycin-enhances-survival-in-a-drosophila-model-of-mitochondrial-disease
#20
Adrienne Wang, Jacob Mouser, Jason Pitt, Daniel Promislow, Matt Kaeberlein
Pediatric mitochondrial disorders are a devastating category of diseases caused by deficiencies in mitochondrial function. Leigh Syndrome (LS) is the most common of these diseases with symptoms typically appearing within the first year of birth and progressing rapidly until death, usually by 6-7 years of age. Our lab has recently shown that genetic inhibition of the mechanistic target of rapamycin (TOR) rescues the short lifespan of yeast mutants with defective mitochondrial function, and that pharmacological inhibition of TOR by administration of rapamycin significantly rescues the shortened lifespan, neurological symptoms, and neurodegeneration in a mouse model of LS...
December 6, 2016: Oncotarget
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