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Mitochondrial calcium uniporter

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https://www.readbyqxmd.com/read/28208618/the-function-of-the-mitochondrial-calcium-uniporter-in-neurodegenerative-disorders
#1
REVIEW
Yajin Liao, Yuan Dong, Jinbo Cheng
The mitochondrial calcium uniporter (MCU)-a calcium uniporter on the inner membrane of mitochondria-controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28198506/inhibition-of-mitochondrial-calcium-uptake-1-in-drosophila-neurons
#2
P G M'Angale, B E Staveley
The mitochondrial calcium uptake 1 (MICU1) is a regulatory subunit of the mitochondrial calcium uniporter that plays an important role in calcium sensing. It contains two EF-hand domains that are well conserved across diverse species from protozoa to plants and metazoans. The loss of MICU1 function in mammals is attributed to several neurological disorders that involve movement dysfunction. The CG4495 gene in Drosophila melanogaster was identified as a putative homolog of MICU1 in the HomoloGene database of the National Centre for Biotechnology Information (NCBI)...
February 8, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28181698/calcium-uptake-via-mitochondrial-uniporter-contributes-to-palmitic-acid-induced-apoptosis-in-mouse-podocytes
#3
Zeting Yuan, Aili Cao, Hua Liu, Henjiang Guo, Yingjun Zang, Yi Wang, Yunman Wang, Hao Wang, Peihao Yin, Wen Peng
Podocytes are component cells of the glomerular filtration barrier, and their loss by apoptosis is the main cause of proteinuria that leads to diabetic nephropathy (DN). Therefore, insights into podocyte apoptosis mechanism would allow a better understanding of DN pathogenesis and thus help develop adequate therapeutic strategies. Here, we investigated the molecular mechanism of palmitic acid-inhibited cell death in mouse podocytes, and found that palmitic acid increased cell death in a dose- and time-dependent manner...
February 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28057556/brain-mitochondrial-calcium-transport-origins-of-the-set-point-concept-and-its-application-to-physiology-and-pathology
#4
David G Nicholls
The transport of calcium across the inner mitochondrial membrane plays a key role in neuronal physiology and pathology. The kinetic responses of the uniporter and efflux pathways are such that a cytosolic free calcium 'set-point' can be established - above which there is net calcium accumulation into the matrix that is reversed when plasma membrane transport lowers cytosolic calcium. Pathological activation of N-methyl-d-aspartate receptor mediated sodium and calcium entry into the neuron, as occurs in stroke and spreading depression, places severe demands on both the ATP-generating and calcium loading capacities of the neuronal mitochondria as the set-point is exceeded...
January 2, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28045016/the-three-herb-formula-shuang-huang-lian-stabilizes-mast-cells-through-activation-of-mitochondrial-calcium-uniporter
#5
Yuan Gao, Rui Hou, Qiaoling Fei, Lei Fang, Yixin Han, Runlan Cai, Cheng Peng, Yun Qi
Mast cells (MCs) are key effector cells of IgE-FcεRI- or MrgprX2-mediated signaling event. Shuang-Huang-Lian (SHL), a herbal formula from Chinese Pharmacopoeia, has been clinically used in type I hypersensitivity. Our previous study demonstrated that SHL exerted a non-negligible effect on MC stabilization. Herein, we sought to elucidate the molecular mechanisms of the prominent anti-allergic ability of SHL. MrgprX2- and IgE-FcεRI-mediated MC activation in vitro and in vivo models were developed by using compound 48/80 (C48/80) and shrimp tropomyosin (ST), respectively...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28039397/physical-exercise-in-aging-human-skeletal-muscle-increases-mitochondrial-calcium-uniporter-expression-levels-and-affects-mitochondria-dynamics
#6
Sandra Zampieri, Cristina Mammucari, Vanina Romanello, Laura Barberi, Laura Pietrangelo, Aurora Fusella, Simone Mosole, Gaia Gherardi, Christian Höfer, Stefan Löfler, Nejc Sarabon, Jan Cvecka, Matthias Krenn, Ugo Carraro, Helmut Kern, Feliciano Protasi, Antonio Musarò, Marco Sandri, Rosario Rizzuto
Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca(2+) homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/28031475/physiological-characterization-of-a-plant-mitochondrial-calcium-uniporter-in-vitro-and-in-vivo
#7
Enrico Teardo, Luca Carraretto, Stephan Wagner, Elide Formentin, Smrutisanjita Behera, Sara De Bortoli, Véronique Larosa, Philippe Fuchs, Fiorella Lo Schiavo, Anna Raffaello, Rosario Rizzuto, Alex Costa, Markus Schwarzländer, Ildiko Szabò
Over the recent years, several proteins that make up the mitochondrial calcium uniporter complex (MCUC) mediating Ca(2+)uptake into the mitochondrial matrix have been identified in mammals, including the channel-forming protein MCU. Although six MCU gene homologs are conserved in the model plant Arabidopsis (Arabidopsis thaliana) in which mitochondria can accumulate Ca(2+), a functional characterization of plant MCU homologs has been lacking. Using electrophysiology, we show that one isoform, AtMCU1, gives rise to a Ca(2+)-permeable channel activity that can be observed even in the absence of accessory proteins implicated in the formation of the active mammalian channel...
February 2017: Plant Physiology
https://www.readbyqxmd.com/read/27995386/the-roles-of-mitochondrial-cation-channels-under-physiological-conditions-and-in-cancer
#8
Ildikò Szabò, Luigi Leanza
Bioenergetics has become central to our understanding of pathological mechanisms as well as the development of new therapeutic strategies and as a tool for gauging disease progression in neurodegeneration, diabetes, cancer, and cardiovascular disease. The view is emerging that inner mitochondrial membrane (IMM) cation channels have a profound effect on mitochondrial function and, consequently, on the metabolic state and survival of the whole cell. Since disruption of the sustained integrity of mitochondria is strongly linked to human disease, pharmacological intervention offers a new perspective concerning neurodegenerative and cardiovascular diseases as well as cancer...
December 20, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27991671/the-mitochondrial-calcium-uniporter-in-the-heart-energetics-and-beyond
#9
Jennifer Q Kwong
Ca(2+) and mitochondria are inextricably linked to cardiac function and dysfunction. Ca(2+) is central to cardiac excitation-contraction coupling and stimulates mitochondrial energy production to fuel contraction. Under pathological conditions of dysregulated Ca(2+) cycling, mitochondrial Ca(2+) overload activates cellular death pathways. Thus, in the cardiomyocyte, the mitochondrial Ca(2+) microdomain is where contraction, energy and death collide. A key component of mitochondrial Ca(2+) signalling is the mitochondrial Ca(2+) uniporter complex (uniplex), an inner membrane Ca(2+) transporter and major pathway of mitochondrial Ca(2+) entry...
December 19, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27943495/the-mitochondrial-complexome-of-arabidopsis-thaliana
#10
Jennifer Senkler, Michael Senkler, Holger Eubel, Tatjana Hildebrandt, Christian Lengwenus, Peter Schertl, Markus Schwarzländer, Stephan Wagner, Ilka Wittig, Hans-Peter Braun
Mitochondria are central to cellular metabolism and energy conversion. In plants they also enable photosynthesis through additional components and functional flexibility. A majority of those processes relies on the assembly of individual proteins to larger protein complexes, some of which operate as large molecular machines. There has been a strong interest in the makeup and function of mitochondrial protein complexes and protein-protein interactions in plants, but the experimental approaches used typically suffer from selectivity or bias...
December 10, 2016: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/27924224/micu1-may-be-a-promising-intervention-target-for-gut-derived-sepsis-induced-by-intra-abdominal-hypertension
#11
Yuxin Leng, Qinggang Ge, Zhiling Zhao, Kun Wang, Gaiqi Yao
Intra-abdominal hypertension (IAH) is a common and serious complication in critically ill patients, for which there is no targeted therapy. IAH-induced dysfunction of intestinal barriers is closely associated with oxidative imbalances, which are considered to provide a pathophysiological basis for subsequent gut-derived sepsis. However, the upstream mechanism that produces oxidative damage during IAH remains unknown. It is not clear whether 'mitochondrial Ca(2+) uptake 1' (MICU1, the key protein regulating the oxidative process) is involved in preventing Ca(2+)m (mitochondrial Ca(2+)) overload...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27924223/mitochondrial-permeability-transition-pore-induction-is-linked-to-formation-of-the-complex-of-atpase-c-subunit-polyhydroxybutyrate-and-inorganic-polyphosphate
#12
P A Elustondo, M Nichols, A Negoda, A Thirumaran, E Zakharian, G S Robertson, E V Pavlov
Mitochondrial permeability transition pore (mPTP) opening allows free movement of ions and small molecules leading to mitochondrial membrane depolarization and ATP depletion that triggers cell death. A multi-protein complex of the mitochondrial ATP synthase has an essential role in mPTP. However, the molecular identity of the central 'pore' part of mPTP complex is not known. A highly purified fraction of mammalian mitochondria containing C-subunit of ATPase (C-subunit), calcium, inorganic polyphosphate (polyP) and polyhydroxybutyrate (PHB) forms ion channels with properties that resemble the native mPTP...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27923677/intact-mitochondrial-ca-2-uniport-is-essential-for-agonist-induced-activation-of-endothelial-nitric-oxide-synthase-enos
#13
Suphachai Charoensin, Emrah Eroglu, Marissa Opelt, Helmut Bischof, Corina T Madreiter-Sokolowski, Andrijana Kirsch, Maria R Depaoli, Saša Frank, Astrid Schrammel, Bernd Mayer, Markus Waldeck-Weiermair, Wolfgang F Graier, Roland Malli
Mitochondrial Ca(2+) uptake regulates diverse endothelial cell functions and has also been related to nitric oxide (NO(•)) production. However, it is not entirely clear if the organelles support or counteract NO(•) biosynthesis by taking up Ca(2+). The objective of this study was to verify whether or not mitochondrial Ca(2+) uptake influences Ca(2+)-triggered NO(•) generation by endothelial NO(•) synthase (eNOS) in an immortalized endothelial cell line (EA.hy926), respective primary human umbilical vein endothelial cells (HUVECs) and eNOS-RFP (red fluorescent protein) expressing human embryonic kidney (HEK293) cells...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27909264/global-ablation-of-the-mitochondrial-calcium-uniporter-increases-glycolysis-in-cortical-neurons-subjected-to-energetic-stressors
#14
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/27879386/mitochondrial-calcium-homeostasis-implications-for-neurovascular-and-neurometabolic-coupling
#15
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...
February 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27859782/inhibition-of-the-mitochondrial-calcium-uniporter-rescues-dopaminergic-neurons-in-pink1-zebrafish
#16
Smijin Soman, Marcus Keatinge, Mahsa Moein, Marc Da Costa, 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
#17
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/27793988/crispr-cas9-mediated-endogenous-c-terminal-tagging-of-trypanosoma-cruzi-genes-reveals-the-acidocalcisome-localization-of-the-inositol-1-4-5-trisphosphate-receptor
#18
Noelia Lander, Miguel A Chiurillo, Melissa Storey, Anibal E Vercesi, Roberto Docampo
Methods for genetic manipulation of Trypanosoma cruzi, the etiologic agent of Chagas disease, have been highly inefficient, and no endogenous tagging of genes has been reported to date. We report here the use of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated gene 9) system for endogenously tagging genes in this parasite. The utility of the method was established by tagging genes encoding proteins of known localization such as TcFCaBP (flagellar calcium binding protein) and TcVP1 (vacuolar proton pyrophosphatase), and two proteins of undefined or disputed localization, the TcMCU (mitochondrial calcium uniporter) and TcIP3R (inositol 1,4,5-trisphosphate receptor)...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27692849/calcium-at-the-center-of-cell-signaling-interplay-between-endoplasmic-reticulum-mitochondria-and-lysosomes
#19
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/27681178/expression-of-the-mitochondrial-calcium-uniporter-in-cardiac-myocytes-improves-impaired-mitochondrial-calcium-handling-and-metabolism-in-simulated-hyperglycemia
#20
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 Ca(2+) uniporter (MCU) is the channel responsible for Ca(2+) uptake in mitochondria, and free mitochondrial Ca(2+) concentration ([Ca(2+)]m) regulates mitochondrial metabolism. Experiments with cardiac myocytes (CM) exposed to simulated hyperglycemia revealed reduced [Ca(2+)]m and MCU protein levels...
December 1, 2016: American Journal of Physiology. Cell Physiology
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