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https://www.readbyqxmd.com/read/28100784/mitochondrial-o-glcnac-transferase-mogt-regulates-mitochondrial-structure-function-and-survival-in-hela-cells
#1
Juliana L Sacoman, Raul Y Dagda, Amanda R Burnham-Marusich, Ruben K Dagda, Patricia M Berninsone
O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. OGT is encoded by a single gene that yields nucleocytosolic and mitochondrial isoforms. To date, the role of the mitochondrial isoform of OGT (mOGT) remains largely unknown. Using high-throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH: ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28099841/targeted-inhibition-of-egfr-and-glutaminase-induces-metabolic-crisis-in-egfr-mutant-lung-cancer
#2
Milica Momcilovic, Sean T Bailey, Jason T Lee, Michael C Fishbein, Clara Magyar, Daniel Braas, Thomas Graeber, Nicholas J Jackson, Johannes Czernin, Ethan Emberley, Matthew Gross, Julie Janes, Andy Mackinnon, Alison Pan, Mirna Rodriguez, Melissa Works, Winter Zhang, Francesco Parlati, Susan Demo, Edward Garon, Kostyantyn Krysan, Tonya C Walser, Steven M Dubinett, Saman Sadeghi, Heather R Christofk, David B Shackelford
Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28095639/early-involvement-of-lysosome-dysfunction-in-the-degeneration-of-cerebral-cortical-neurons-caused-by-the-lipid-peroxidation-product-4-hydroxynonenal
#3
Shi Zhang, Erez Eitan, Mark P Mattson
Free radical-mediated oxidative damage to proteins, lipids and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy - lysosome pathway in rat primary cortical neurons...
January 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28093608/spatiotemporal-drivers-of-energy-expenditure-in-a-coastal-marine-fish
#4
Jacob W Brownscombe, Steven J Cooke, Andy J Danylchuk
Animal behavior and energy expenditure often vary significantly across the landscape, and quantifying energy expenditure over space and time provides mechanistic insight into ecological dynamics. Yet, spatiotemporal variability in energy expenditure has rarely been explored in fully aquatic species such as fish. Our objective was to quantify spatially explicit energy expenditure for a tropical marine teleost fish, bonefish (Albula vulpes), to examine how bonefish energetics vary across landscape features and temporal factors...
January 16, 2017: Oecologia
https://www.readbyqxmd.com/read/28093355/evaluating-the-therapeutic-potential-of-idebenone-and-related-quinone-analogues-in-leber-hereditary-optic-neuropathy
#5
Patrick Yu-Wai-Man, Devorah Soiferman, David G Moore, Florence Burté, Ann Saada
Leber hereditary optic neuropathy (LHON) is an important cause of mitochondrial blindness among young adults. In this study, we investigated the potential of four quinone analogues (CoQ1, CoQ10, decylubiquinone and idebenone) in compensating for the deleterious effect of the m.11778G>A mitochondrial DNA mutation. The LHON fibroblast cell lines tested exhibited reduced cell growth, impaired mitochondrial bioenergetics and elevated levels of reactive oxygen species (ROS). Idebenone increased ATP production and reduced ROS levels, but the effect was partial and cell-specific...
January 13, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28092677/wnt-%C3%AE-catenin-signaling-regulates-mitochondrial-activity-to-alter-the-oncogenic-potential-of-melanoma-in-a-pten-dependent-manner
#6
K Brown, P Yang, D Salvador, R Kulikauskas, H Ruohola-Baker, A M Robitaille, A J Chien, R T Moon, V Sherwood
Aberrant regulation of WNT/β-catenin signaling has a crucial role in the onset and progression of cancers, where the effects are not always predictable depending on tumor context. In melanoma, for example, models of the disease predict differing effects of the WNT/β-catenin pathway on metastatic progression. Understanding the processes that underpin the highly context-dependent nature of WNT/β-catenin signaling in tumors is essential to achieve maximal therapeutic benefit from WNT inhibitory compounds. In this study, we have found that expression of the tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), alters the invasive potential of melanoma cells in response to WNT/β-catenin signaling, correlating with differing metabolic profiles...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28087734/increased-mitophagy-in-the-skeletal-muscle-of-spinal-and-bulbar-muscular-atrophy-patients
#7
Doriana Borgia, Adriana Malena, Marco Spinazzi, Maria Andrea Desbats, Leonardo Salviati, Aaron P Russell, Giovanni Miotto, Laura Tosatto, Elena Pegoraro, Gianni Sorarù, Maria Pennuto, Lodovica Vergani
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by polyglutamine expansion in the androgen receptor (AR) and characterized by the loss of lower motor neurons. Here we investigated pathological processes occurring in muscle biopsy specimens derived from SBMA patients and, as controls, age-matched healthy subjects and patients suffering from amyotrophic lateral sclerosis (ALS) and neurogenic atrophy. We detected atrophic fibers in the muscle of SBMA, ALS and neurogenic atrophy patients...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28087333/nicotinamide-nucleotide-transhydrogenase-activity-impacts-mitochondrial-redox-balance-and-the-development-of-hypertension-in-mice
#8
Igor Leskov, Amber Neville, Xinggui Shen, Sibile Pardue, Christopher G Kevil, D Neil Granger, David M Krzywanski
Oxidant stress contributes to the initiation and progression of hypertension (HTN) by enhancing endothelial dysfunction and/or causing perturbations in nitric oxide homeostasis. Differences in mitochondrial function may augment this process and provide insight into why age of onset and clinical outcomes differ among individuals from distinct ethnic groups. We have previously demonstrated that variation in normal mitochondrial function and oxidant production exists in endothelial cells from individuals of Caucasian and African-American ethnicity and that this variation contributes to endothelial dysfunction...
December 16, 2016: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/28079313/postischemic-inflammation-in-acute-stroke
#9
REVIEW
Simone Vidale, Arturo Consoli, Marco Arnaboldi, Domenico Consoli
Cerebral ischemia is caused by arterial occlusion due to a thrombus or an embolus. Such occlusion induces multiple and concomitant pathophysiological processes that involve bioenergetic failure, acidosis, loss of cell homeostasis, excitotoxicity, and disruption of the blood-brain barrier. All of these mechanisms contribute to neuronal death, mainly via apoptosis or necrosis. The immune system is involved in this process in the early phases after brain injury, which contributes to potential enlargement of the infarct size and involves the penumbra area...
January 2017: Journal of Clinical Neurology
https://www.readbyqxmd.com/read/28077389/enhanced-oxidative-capacity-of-ground-squirrel-brain-mitochondria-during-hibernation
#10
Mallory A Ballinger, Christine Schwartz, Matthew T Andrews
During hibernation, thirteen-lined ground squirrels (Ictidomys tridecemlineatus) regularly cycle between bouts of torpor and interbout arousal (IBA).  Most of the brain is electrically quiescent during torpor, but regains activity quickly upon arousal to IBA resulting in extreme oscillations in energy demand during hibernation.  We predicted increased functional capacity of brain mitochondria during hibernation compared to spring to accommodate the variable energy demands of hibernation.  To address this hypothesis, we examined mitochondrial bioenergetics in the ground squirrel brain across three time points: spring (SP), torpor (TOR), and IBA...
January 11, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28077358/biological-signaling-by-carbon-monoxide-and-carbon-monoxide-releasing-molecules-co-rms
#11
Roberto Motterlini, Roberta Foresti
Carbon monoxide (CO) is continuously produced in mammalian cells during degradation of heme. It is a stable gaseous molecule that reacts selectively with transition metals in a specific redox state and these characteristics restrict the interaction of CO with defined biological targets that transduce its signaling activity. Because of the high affinity of CO for ferrous heme, these targets can be grouped into heme-containing proteins, representing a large variety of sensors and enzymes with a series of diverse function in the cell and the organism...
January 11, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28076767/-s-pot-on-mitochondria-cannabinoids-disrupt-cellular-respiration-to-limit-neuronal-activity
#12
Tibor Harkany, Tamas L Horvath
Classical views posit G protein-coupled cannabinoid receptor 1s (CB1Rs) at the cell surface with cytosolic Giα-mediated signal transduction. Hebert-Chatelain et al. (2016) instead place CB1Rs at mitochondria limiting neuronal respiration by soluble adenylyl cyclase-dependent modulation of complex I activity. Thus, neuronal bioenergetics link to synaptic plasticity and, globally, learning and memory.
January 10, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28072864/1h-nmr-metabolomics-reveals-association-of-high-expression-of-inositol-1-4-5-trisphosphate-receptor-and-metabolites-in-breast-cancer-patients
#13
Aru Singh, Raj Kumar Sharma, Megha Chagtoo, Gaurav Agarwal, Nelson George, Neeraj Sinha, Madan M Godbole
1H NMR is used to detect alterations in metabolites and their linkage to metabolic processes in a number of pathological conditions including breast cancer. Inositol 1, 4, 5 trisphosphate (IP3R) receptor is an intracellular calcium channel known to regulate metabolism and cellular bioenergetics. Its expression is up regulated in a number of cancers. However, its linkage to metabolism in disease conditions has not been evaluated. This study was designed to determine the association if any, of these metabolites with altered expression of IP3R in breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28072841/a-small-insulinomimetic-molecule-also-improves-insulin-sensitivity-in-diabetic-mice
#14
Sandip Mukherjee, Mrittika Chattopadhyay, Sushmita Bhattacharya, Suman Dasgupta, Sahid Hussain, Saitanya K Bharadwaj, Dhrubajyoti Talukdar, Abul Usmani, Bhola S Pradhan, Subeer S Majumdar, Pronobesh Chattopadhyay, Satinath Mukhopadhyay, Tushar K Maity, Mihir K Chaudhuri, Samir Bhattacharya
Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O2)2(dmpz)], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1...
2017: PloS One
https://www.readbyqxmd.com/read/28070278/entanglement-is-a-costly-life-history-stage-in-large-whales
#15
Julie van der Hoop, Peter Corkeron, Michael Moore
Individuals store energy to balance deficits in natural cycles; however, unnatural events can also lead to unbalanced energy budgets. Entanglement in fishing gear is one example of an unnatural but relatively common circumstance that imposes energetic demands of a similar order of magnitude and duration of life-history events such as migration and pregnancy in large whales. We present two complementary bioenergetic approaches to estimate the energy associated with entanglement in North Atlantic right whales, and compare these estimates to the natural energetic life history of individual whales...
January 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28066524/bioenergetic-differences-during-walking-and-running-in-transfemoral-amputee-runners-using-articulating-and-non-articulating-knee-prostheses
#16
M Jason Highsmith, Jason T Kahle, Rebecca M Miro, Larry J Mengelkoch
Transfemoral amputation (TFA) patients require considerably more energy to walk and run than non-amputees. The purpose of this study was to examine potential bioenergetic differences (oxygen uptake (VO2), heart rate (HR), and ratings of perceived exertion (RPE)) for TFA patients utilizing a conventional running prosthesis with an articulating knee mechanism versus a running prosthesis with a non-articulating knee joint. Four trained TFA runners (n = 4) were accommodated to and tested with both conditions. VO2 and HR were significantly lower (p ≤ 0...
September 2016: Technology and Innovation
https://www.readbyqxmd.com/read/28063512/tackling-guanidinoacetic-acid-for-advanced-cellular-bioenergetics
#17
REVIEW
Sergej M Ostojic
Tissues with high-energy output, such as the brain and skeletal muscle, suffer the most from impaired or depleted energy levels, with innovative nutritional approaches needed to effectively tackle metabolic deficits in bioenergetics. Here, we highlight the role of guanidinoacetic acid in the control and provision of cellular energy by its interaction with cellular transporters for taurine (SLC6 A6) and γ-aminobutyric acid (SLC6 A13), previously dismissed as "untargetable" carriers by other bioenergetics therapeutics...
February 2017: Nutrition
https://www.readbyqxmd.com/read/28063266/antibiotics-may-trigger-mitochondrial-dysfunction-inducing-psychiatric-disorders
#18
George B Stefano, Joshua Samuel, Richard M Kream
Clinical usage of several classes of antibiotics is associated with moderate to severe side effects due to the promotion of mitochondrial dysfunction. We contend that this may be due to perturbation of unique evolutionary relationships that link selective biochemical and molecular aspects of mitochondrial biology to conserved enzymatic processes derived from bacterial progenitors. Operationally, stereo-selective conformational matching between mitochondrial respiratory complexes, cytosolic and nuclear signaling complexes appears to support the conservation of a critically important set of chemical messengers required for existential regulation of homeostatic cellular processes...
January 7, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28062752/arabidopsis-seed-mitochondria-are-bioenergetically-active-immediately-upon-imbibition-and-specialize-via-biogenesis-in-preparation-for-autotrophic-growth
#19
Gael Paszkiewicz, Jose Manuel Gualberto, Abdelilah Benamar, David Macherel, David C Logan
Seed germination is a vital developmental transition for production of progeny by sexual reproduction in spermatophytes. Quiescent cells in non-dormant dry embryos are reawakened first by imbibition and then by perception of germination triggers. Reanimated tissues enter into a germination program requiring energy for expansion growth. However, germination requires that embryonic tissues develop to support the more energy-demanding processes of cell division and organogenesis of the new seedling. Reactivation of mitochondria to supply the required energy is thus a key process underpinning germination and seedling survival...
January 6, 2017: Plant Cell
https://www.readbyqxmd.com/read/28062576/cardiolipin-regulates-mitophagy-through-the-pkc-pathway
#20
Zheni Shen, Yiran Li, Alexander N Gasparski, Hagai Abeliovich, Miriam L Greenberg
Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is important for cardiovascular health, and perturbation of CL metabolism is implicated in cardiovascular disease (CVD). While the role of CL in mitochondrial function, biogenesis, and genome stability has been studied, recent findings indicate that it is essential for functions apart from mitochondrial bioenergetics. In this study, we report that mitophagy is perturbed in CL deficient yeast cells. Mutants of autophagy/mitophagy genes ATG8, ATG18 and ATG32 synthetically interact with CL synthase mutant crd1Δ CL-deficient cells exhibited decreased GFP-tagged mitochondrial proteins inside the vacuole and decreased free GFP, consistent with decreased mitophagy...
January 5, 2017: Journal of Biological Chemistry
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