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https://www.readbyqxmd.com/read/27909264/global-ablation-of-the-mitochondrial-calcium-uniporter-increases-glycolysis-in-cortical-neurons-subjected-to-energetic-stressors
#1
Matthew Nichols, Pia A Elustondo, Jordan Warford, Aruloli Thirumaran, Evgeny V Pavlov, George S Robertson
The effects of global mitochondrial calcium (Ca(2+)) uniporter (MCU) deficiency on hypoxic-ischemic (HI) brain injury, neuronal Ca(2+) handling, bioenergetics and hypoxic preconditioning (HPC) were examined. Forebrain mitochondria isolated from global MCU nulls displayed markedly reduced Ca(2+) uptake and Ca(2+)-induced opening of the membrane permeability transition pore. Despite evidence that these effects should be neuroprotective, global MCU nulls and wild-type (WT) mice suffered comparable HI brain damage...
December 1, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27879545/epstein-barr-virus-associated-mucocutaneous-ulcer-in-a-patient-with-t-cell-acute-lymphoblastic-leukemia-importance-of-accurate-diagnosis-and-conservative-management
#2
Anant Vatsayan, Ashish Gupta, Sanjay Ahuja, Rachel Egler, Rose C Beck, Yousif Matloub
Epstein-Barr virus-associated mucocutaneous ulcer (EBV-MCU) is a recently characterized entity that falls under the spectrum of EBV-lymphoproliferative disorders. First described in 2010 by Dojcinov et al, it is an EBV-driven localized proliferation of B cells, occurring in mucocutaneous tissues including the skin, the oropharynx, and the gastrointestinal tract of immunosuppressed patients in the absence of an intact T-cell repertoire. Typically, it has been described in elderly patients with age-related immunosenescence and patients who are on immunosuppressive therapy...
November 22, 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27879386/mitochondrial-calcium-homeostasis-implications-for-neurovascular-and-neurometabolic-coupling
#3
REVIEW
Sridhar S Kannurpatti
Mitochondrial function is critical to maintain high rates of oxidative metabolism supporting energy demands of both spontaneous and evoked neuronal activity in the brain. Mitochondria not only regulate energy metabolism, but also influence neuronal signaling. Regulation of "energy metabolism" and "neuronal signaling" (i.e. neurometabolic coupling), which are coupled rather than independent can be understood through mitochondria's integrative functions of calcium ion (Ca(2+)) uptake and cycling. While mitochondrial Ca(2+) do not affect hemodynamics directly, neuronal activity changes are mechanistically linked to functional hyperemic responses (i...
November 22, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27859782/inhibition-of-the-mitochondrial-calcium-uniporter-mcu-rescues-dopaminergic-neurons-in-pink1-zebrafish
#4
Smijin Soman, Marcus Keatinge, Mahsa Moein, Marc DaCosta, Heather Mortiboys, Alexander Skupin, Sreedevi Sugunan, Michal Bazala, Jacek Kuznicki, Oliver Bandmann
Mutations in PTEN-induced putative kinase 1 (PINK1) are a cause of early onset Parkinson's disease (PD). Loss of PINK1 function causes dysregulation of mitochondrial calcium homeostasis, resulting in mitochondrial dysfunction and neuronal cell death. We report that both genetic and pharmacological inactivation of the mitochondrial calcium uniporter (MCU), located in the inner mitochondrial membrane, prevents dopaminergic neuronal cell loss in pink1(Y431) * mutant zebrafish (Danio rerio) via rescue of mitochondrial respiratory chain function...
November 12, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27827394/mitochondrial-ca-2-uptake-controls-actin-cytoskeleton-dynamics-during-cell-migration
#5
Julien Prudent, Nikolay Popgeorgiev, Rudy Gadet, Mathieu Deygas, Ruth Rimokh, Germain Gillet
Intracellular Ca(2+) signaling regulates cell migration by acting on cytoskeleton architecture, cell directionality and focal adhesions dynamics. In migrating cells, cytosolic Ca(2+) pool and Ca(2+) pulses are described as key components of these effects. Whereas the role of the mitochondrial calcium homeostasis and the Mitochondria Cacium Uniporter (MCU) in cell migration were recently highlighted in vivo using the zebrafish model, their implication in actin cystokeleton dynamics and cell migration in mammals is not totally characterized...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27819749/does-mri-help-in-the-pre-operative-evaluation-of-pelvic-fracture-urethral-distraction-defect-a-pilot-study
#6
Rajadoss Muthukrishna Pandian, Nirmal Thampi John, Anu Eapen, B Antonisamy, Antony Devasia, Nitin Kekre
OBJECTIVES: To study the usefulness of MRI in preoperative evaluation of PFUDD. Can MRI provide additional information on urethral distraction defect (UDD) and cause of erectile dysfunction (ED)? MATERIALS AND METHODS: In this prospective study, consecutive male patients presenting with PFUDD were included from Feb 2011 till Dec 2012. Those with traumatic spinal cord injury and pre-existing ED were excluded. Patients were assessed using IIEF questionnaire, retrograde urethrogram and micturating cystourethrogram (RGU+MCU) and MRI pelvis...
November 2, 2016: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/27818145/a-micu1-splice-variant-confers-high-sensitivity-to-the-mitochondrial-ca-2-uptake-machinery-of-skeletal-muscle
#7
Denis Vecellio Reane, Francesca Vallese, Vanessa Checchetto, Laura Acquasaliente, Gaia Butera, Vincenzo De Filippis, Ildikò Szabò, Giuseppe Zanotti, Rosario Rizzuto, Anna Raffaello
Skeletal muscle is a dynamic organ, characterized by an incredible ability to rapidly increase its rate of energy consumption to sustain activity. Muscle mitochondria provide most of the ATP required for contraction via oxidative phosphorylation. Here we found that skeletal muscle mitochondria express a unique MCU complex containing an alternative splice isoform of MICU1, MICU1.1, characterized by the addition of a micro-exon that is sufficient to greatly modify the properties of the MCU. Indeed, MICU1.1 binds Ca(2+) one order of magnitude more efficiently than MICU1 and, when heterodimerized with MICU2, activates MCU current at lower Ca(2+) concentrations than MICU1-MICU2 heterodimers...
November 17, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27777824/the-course-of-the-terminal-posterior-interosseous-nerve-and-its-relationship-with-wrist-arthroscopy-portals
#8
Yongwei Pan, Leung-Kim Hung
Purpose The terminal branches of the posterior interosseous nerve (PIN) are the main articular branch on the dorsal aspect of the wrist. Its relationship to dorsal wrist arthroscopic portals has not yet been elucidated. The purpose of this study was to quantitatively describe the anatomical relationships between the dorsal wrist arthroscopic portals and the PIN. Methods Dorsal wrist arthroscopic portals were established in 28 cadaver extremities, after which the limbs were dissected. Measurements were taken from the portals to the PIN...
November 2016: Journal of Wrist Surgery
https://www.readbyqxmd.com/read/27692849/calcium-at-the-center-of-cell-signaling-interplay-between-endoplasmic-reticulum-mitochondria-and-lysosomes
#9
REVIEW
Anna Raffaello, Cristina Mammucari, Gaia Gherardi, Rosario Rizzuto
In recent years, rapid discoveries have been made relating to Ca(2+) handling at specific organelles that have important implications for whole-cell Ca(2+) homeostasis. In particular, the structures of the endoplasmic reticulum (ER) Ca(2+) channels revealed by electron cryomicroscopy (cryo-EM), continuous updates on the structure, regulation, and role of the mitochondrial calcium uniporter (MCU) complex, and the analysis of lysosomal Ca(2+) signaling are milestones on the route towards a deeper comprehension of the complexity of global Ca(2+) signaling...
December 2016: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27689916/a-novel-puborectalis-muscle-artificial-anal-sphincter-system-with-the-module-of-sensory-perception
#10
Hao Wu, Zhiwu Wang, Guozheng Yan, Wentian Jin, Shan Lu, Zerun Zhou
This article presents a novel puborectalis muscle artificial anal sphincter system (PM-AASS) with the module of sensory perception for treating severe faecal incontinence (FI). Due to the implantable feature of PM-AASS, this system applied low-power design and the total energy consumption could drop to 48.8 Ah/d. To reduce the injury of intestine and the pressure exerted on intestine, the actuator, including the structure of tings and the robot mechanism, of PM-AASS was presented and the middle ring was optimised...
February 2017: Journal of Medical Engineering & Technology
https://www.readbyqxmd.com/read/27681178/expression-of-the-mitochondrial-calcium-uniporter-in-cardiac-myocytes-improves-impaired-mitochondrial-calcium-handling-and-metabolism-in-simulated-hyperglycemia
#11
Julieta Diaz-Juarez, Jorge Suarez, Federico Cividini, Brian T Scott, Tanja Diemer, Anzhi Dai, Wolfgang H Dillmann
Diabetic cardiomyopathy is associated with metabolic changes including decreased glucose oxidation (Gox) and increased fatty acid oxidation (FAox), which result in cardiac energetic deficiency. Diabetic hyperglycemia is a pathophysiological mechanism that triggers multiple maladaptive phenomena. The mitochondrial calcium uniporter (MCU) is the channel responsible for Ca(2+) uptake in mitochondria and free mitochondrial calcium concentration ([Ca(2+)]m) regulates mitochondrial metabolism. Experiments with cardiac myocytes (CM) exposed to simulated hyperglycemia revealed both reduced [Ca(2+)]m and MCU protein levels...
September 28, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27667318/the-impact-of-the-context-and-recruitment-materials-on-nondonors-willingness-to-donate-blood
#12
Barbara M Masser, Christopher R France, Lina K Himawan, Melissa K Hyde, Geoff Smith
BACKGROUND: Anxiety is a frequently cited barrier to blood donor recruitment. Although the mere presence of donation paraphernalia can heighten anxiety for some individuals, such stimuli are a necessary and unavoidable part of donation. Drawing on France and colleagues' research on tailored donor education and coping materials, the current study assessed whether modifying recruitment materials could improve donor recruitment in a context where anxiety is heightened. STUDY DESIGN AND METHODS: A field study comprising a 2 (presence or absence of a mobile blood collection unit [MCU]) × 2 (recruitment brochure: standard, coping) between-subjects design was conducted with 922 nondonors who believed themselves eligible to donate blood...
September 25, 2016: Transfusion
https://www.readbyqxmd.com/read/27665468/mitochondrial-ca-2-uptake-pathways
#13
Pia A Elustondo, Matthew Nichols, George S Robertson, Evgeny V Pavlov
Calcium (Ca(2+)) plays diverse roles in all living organisms ranging from bacteria to humans. It is a structural element for bones, an essential mediator of excitation-contraction coupling, and a universal second messenger in the regulation of ion channel, enzyme and gene expression activities. In mitochondria, Ca(2+) is crucial for the control of energy production and cellular responses to metabolic stress. Ca(2+) uptake by the mitochondria occurs by the uniporter mechanism. The Mitochondrial Ca2+ Uniporter (MCU) protein has recently been identified as a core component responsible for mitochondrial Ca(2+) uptake...
September 24, 2016: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/27648837/mir-138-and-mir-25-downregulate-mcu-causing-pulmonary-arterial-hypertension-s-cancer-phenotype
#14
Zhigang Hong, Kuang-Hueih Chen, Asish Dasgupta, Francois Potus, Kimberly Dunham-Snary, Sebastien Bonnet, Lian Tian, Jennifer Fu, Sandra Breuils-Bonnet, Steeve Provencher, Danchen Wu, Jeffrey Mewburn, Mark L Ormiston, Stephen L Archer
RATIONALE: Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy characterized by excessive pulmonary artery smooth muscle cells (PASMC) proliferation, migration, and apoptosis-resistance. This cancer-like phenotype is promoted by increased cytosolic calcium ([Ca2+]cyto), aerobic glycolysis and mitochondrial fission. OBJECTIVES: To determine how changes in mitochondrial calcium uniporter complex (MCUC) function influence mitochondrial dynamics and contribute to PAH's cancer-like phenotype...
September 20, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27642082/prmt1-mediated-methylation-of-micu1-determines-the-ucp2-3-dependency-of-mitochondrial-ca-2-uptake-in-immortalized-cells
#15
Corina T Madreiter-Sokolowski, Christiane Klec, Warisara Parichatikanond, Sarah Stryeck, Benjamin Gottschalk, Sergio Pulido, Rene Rost, Emrah Eroglu, Nicole A Hofmann, Alexander I Bondarenko, Tobias Madl, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
Recent studies revealed that mitochondrial Ca(2+) channels, which control energy flow, cell signalling and death, are macromolecular complexes that basically consist of the pore-forming mitochondrial Ca(2+) uniporter (MCU) protein, the essential MCU regulator (EMRE), and the mitochondrial Ca(2+) uptake 1 (MICU1). MICU1 is a regulatory subunit that shields mitochondria from Ca(2+) overload. Before the identification of these core elements, the novel uncoupling proteins 2 and 3 (UCP2/3) have been shown to be fundamental for mitochondrial Ca(2+) uptake...
September 19, 2016: Nature Communications
https://www.readbyqxmd.com/read/27642048/the-m-aaa-protease-associated-with-neurodegeneration-limits-mcu-activity-in-mitochondria
#16
Tim König, Simon E Tröder, Kavya Bakka, Anne Korwitz, Ricarda Richter-Dennerlein, Philipp A Lampe, Maria Patron, Mareike Mühlmeister, Sergio Guerrero-Castillo, Ulrich Brandt, Thorsten Decker, Ines Lauria, Angela Paggio, Rosario Rizzuto, Elena I Rugarli, Diego De Stefani, Thomas Langer
Mutations in subunits of mitochondrial m-AAA proteases in the inner membrane cause neurodegeneration in spinocerebellar ataxia (SCA28) and hereditary spastic paraplegia (HSP7). m-AAA proteases preserve mitochondrial proteostasis, mitochondrial morphology, and efficient OXPHOS activity, but the cause for neuronal loss in disease is unknown. We have determined the neuronal interactome of m-AAA proteases in mice and identified a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca(2+) uniporter MCU...
October 6, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27637331/strategic-positioning-and-biased-activity-of-the-mitochondrial-calcium-uniporter-in-cardiac-muscle
#17
Sergio De La Fuente, Celia Fernandez-Sanz, Caitlin Vail, Elorm J Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Dewight Williams, Toren Finkel, Elizabeth Murphy, Suresh K Joseph, Shey-Shing Sheu, György Csordás
Control of myocardial energetics by Ca(2+) signal propagation to the mitochondrial matrix includes local Ca(2+) delivery from sarcoplasmic reticulum (SR) ryanodine receptors (RyR2) to the inner mitochondrial membrane (IMM) Ca(2+) uniporter (mtCU). mtCU activity in cardiac mitochondria is relatively low, whereas the IMM surface is large, due to extensive cristae folding. Hence, stochastically distributed mtCU may not suffice to support local Ca(2+) transfer. We hypothesized that mtCU concentrated at mitochondria-SR associations would promote the effective Ca(2+) transfer...
October 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27627464/privileged-crosstalk-between-trpv1-channels-and-mitochondrial-calcium-shuttling-machinery-controls-nociception
#18
Iulia I Nita, Yaki Caspi, Sagi Gudes, Dimitri Fishman, Shaya Lev, Michal Hersfinkel, Israel Sekler, Alexander M Binshtok
The nociceptive noxious heat-activated receptor - TRPV1, conducts calcium and sodium, thus producing a depolarizing receptor potential, leading to activation of nociceptive neurons. TRPV1-mediated calcium and sodium influx is negatively modulated by calcium, via calcium-dependent desensitization of TRPV1 channels. A mitochondrial Ca(2+) uniporter - MCU, controls mitochondrial Ca(2+) entry while a sodium/calcium transporter - NCLX shapes calcium and sodium transients by mediating sodium entry into and removing calcium from the mitochondria...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27606689/resveratrol-specifically-kills-cancer-cells-by-a-devastating-increase-in-the-ca2-coupling-between-the-greatly-tethered-endoplasmic-reticulum-and-mitochondria
#19
Corina T Madreiter-Sokolowski, Benjamin Gottschalk, Warisara Parichatikanond, Emrah Eroglu, Christiane Klec, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
BACKGROUND/AIMS: Resveratrol and its derivate piceatannol are known to induce cancer cell-specific cell death. While multiple mechanisms of actions have been described including the inhibition of ATP synthase, changes in mitochondrial membrane potential and ROS levels, the exact mechanisms of cancer specificity of these polyphenols remain unclear. This paper is designed to reveal the molecular basis of the cancer-specific initiation of cell death by resveratrol and piceatannol. METHODS: The two cancer cell lines EA...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27589986/unsuspected-serotonin-toxicity-in-the-icu
#20
Catharina E van Ewijk, Gabriel E Jacobs, Armand R J Girbes
BACKGROUND: Delirium is a frequently occurring syndrome in patients admitted to the intensive care unit (ICU) or medium care unit (MCU), yet the pathophysiology remains poorly understood. An excess of central serotonin can lead to an altered mental status, associated with autonomic hyperactivity, and neuromuscular excitation. Drugs with serotonergic properties are frequently and for prolonged periods administered to ICU/MCU patients. Therefore, central serotonergic toxicity may constitute a predisposing, contributing or precipitating factor in the emergence of delirium...
December 2016: Annals of Intensive Care
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