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Mitochondrial calcium uniporter

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https://www.readbyqxmd.com/read/28396416/proteolytic-control-of-the-mitochondrial-calcium-uniporter-complex
#1
Chen-Wei Tsai, Yujiao Wu, Ping-Chieh Pao, Charles B Phillips, Carole Williams, Christopher Miller, Matthew Ranaghan, Ming-Feng Tsai
The mitochondrial calcium uniporter is a Ca(2+)-activated Ca(2+) channel complex mediating mitochondrial Ca(2+) uptake, a process crucial for Ca(2+) signaling, bioenergetics, and cell death. The uniporter is composed of the pore-forming MCU protein, the gatekeeping MICU1 and MICU2 subunits, and EMRE, a single-pass membrane protein that links MCU and MICU1 together. As a bridging subunit required for channel function, EMRE could paradoxically inhibit uniporter complex formation if expressed in excess. Here, we show that mitochondrial mAAA proteases AFG3L2 and SPG7 rapidly degrade unassembled EMRE using the energy of ATP hydrolysis...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28388446/phosphorylation-of-dynamin-related-protein-1-at-ser616-regulates-mitochondrial-fission-and-is-involved-in-mitochondrial-calcium-uniporter-mediated-neutrophil-polarization-and-chemotaxis
#2
Xianchong Zheng, Mimi Chen, Xiaojing Meng, Xinwei Chu, Chunqing Cai, Fei Zou
During an inflammatory response, polarization of neutrophils is necessary for effective chemotaxis and bacterial endocytosis. Ca(2+) uptake into mitochondria through the mitochondrial calcium uniporter (MCU) is crucial for cell metabolism, signaling and survival; however, the physiological role of MCU in human neutrophils remains unclear. Here we show that MCU is vital for the polarization and chemotaxis of neutrophils. Activation of MCU by spermine promotes neutrophil polarization and chemotaxis, whereas inhibition of MCU by Ru360 blunts both processes...
April 4, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28351840/macrophages-utilize-the-mitochondrial-calcium-uniporter-for-profibrotic-polarization
#3
Linlin Gu, Jennifer L Larson-Casey, A Brent Carter
Fibrosis in multiple organs, including the liver, kidney, and lung, often occurs secondary to environmental exposure. Asbestos exposure is one important environmental cause of lung fibrosis. The mechanisms that mediate fibrosis is not fully understood, although mitochondrial oxidative stress in alveolar macrophages is critical for fibrosis development. Mitochondrial Ca(2+) levels can be associated with production of reactive oxygen species. Here, we show that patients with asbestosis have higher levels of mitochondrial Ca(2+) compared with normal patients...
March 28, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28337252/small-interfering-rna-targeting-mitochondrial-calcium-uniporter-improves-cardiomyocyte-cell-viability-in-hypoxia-reoxygenation-injury-by-reducing-calcium-overload
#4
Yuriana Oropeza-Almazán, Eduardo Vázquez-Garza, Héctor Chapoy-Villanueva, Guillermo Torre-Amione, Gerardo García-Rivas
Intracellular Ca(2+) mishandling is an underlying mechanism in hypoxia/reoxygenation (H/R) injury that results in mitochondrial dysfunction and cardiomyocytes death. These events are mediated by mitochondrial Ca(2+) (mCa(2+)) overload that is facilitated by the mitochondrial calcium uniporter (MCU) channel. Along this line, we evaluated the effect of siRNA-targeting MCU in cardiomyocytes subjected to H/R injury. First, cardiomyocytes treated with siRNA demonstrated a reduction of MCU expression by 67%, which resulted in significant decrease in mitochondrial Ca(2+) transport...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28325874/ion-and-inhibitor-binding-of-the-double-ring-ion-selectivity-filter-of-the-mitochondrial-calcium-uniporter
#5
Chan Cao, Shuqing Wang, Tanxing Cui, Xun-Cheng Su, James J Chou
The calcium (Ca(2+)) uniporter of mitochondria is a holocomplex consisting of the Ca(2+)-conducting channel, known as mitochondrial calcium uniporter (MCU), and several accessory and regulatory components. A previous electrophysiology study found that the uniporter has high Ca(2+) selectivity and conductance and this depends critically on the conserved amino acid sequence motif, DXXE (Asp-X-X-Glu) of MCU. A recent NMR structure of the MCU channel from Caenorhabditis elegans revealed that the DXXE forms two parallel carboxylate rings at the channel entrance that seem to serve as the ion selectivity filter, although direct ion interaction of this structural motif has not been addressed...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28306510/redox-control-of-mitochondrial-calcium-uptake
#6
Nicolas Demaurex, Manon Rosselin
Dong et al. (2017) establish how the mitochondrial Ca(2+) uniporter (MCU) integrates Ca(2+) and oxidative stress signals by identifying a cysteine residue that controls MCU channel activity, a mechanism causing mitochondrial Ca(2+) overload and cell death during oxidative stress.
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28280417/hydrogen-peroxide-attenuates-refilling-of-intracellular-calcium-store-in-mouse-pancreatic-acinar-cells
#7
Mi Na Yoon, Dong Kwan Kim, Se Hoon Kim, Hyung Seo Park
Intracellular calcium (Ca(2+)) oscillation is an initial event in digestive enzyme secretion of pancreatic acinar cells. Reactive oxygen species are known to be associated with a variety of oxidative stress-induced cellular disorders including pancreatitis. In this study, we investigated the effect of hydrogen peroxide (H2O2) on intracellular Ca(2+) accumulation in mouse pancreatic acinar cells. Perfusion of H2O2 at 300 µM resulted in additional elevation of intracellular Ca(2+) levels and termination of oscillatory Ca(2+) signals induced by carbamylcholine (CCh) in the presence of normal extracellular Ca(2+)...
March 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28273446/tissue-specific-mitochondrial-decoding-of-cytoplasmic-ca-2-signals-is-controlled-by-the-stoichiometry-of-micu1-2-and-mcu
#8
Melanie Paillard, György Csordás, Gergö Szanda, Tünde Golenár, Valentina Debattisti, Adam Bartok, Nadan Wang, Cynthia Moffat, Erin L Seifert, András Spät, György Hajnóczky
Mitochondrial Ca(2+) uptake through the Ca(2+) uniporter supports cell functions, including oxidative metabolism, while meeting tissue-specific calcium signaling patterns and energy needs. The molecular mechanisms underlying tissue-specific control of the uniporter are unknown. Here, we investigated a possible role for tissue-specific stoichiometry between the Ca(2+)-sensing regulators (MICUs) and pore unit (MCU) of the uniporter. Low MICU1:MCU protein ratio lowered the [Ca(2+)] threshold for Ca(2+) uptake and activation of oxidative metabolism but decreased the cooperativity of uniporter activation in heart and skeletal muscle compared to liver...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28253172/correction-dual-functions-of-a-small-regulatory-subunit-in-the-mitochondrial-calcium-uniporter-complex
#9
Ming-Feng Tsai, Charles B Phillips, Matthew Ranaghan, Chen-Wei Tsai, Yujiao Wu, Carole Willliams, Christopher Miller
No abstract text is available yet for this article.
March 2, 2017: ELife
https://www.readbyqxmd.com/read/28208618/the-function-of-the-mitochondrial-calcium-uniporter-in-neurodegenerative-disorders
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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