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https://www.readbyqxmd.com/read/28740830/structure-activity-regulation-and-role-of-the-mitochondrial-calcium-uniporter-in-health-and-disease
#1
REVIEW
Cristina Mammucari, Gaia Gherardi, Rosario Rizzuto
Mitochondrial Ca(2+) uptake plays a pivotal role both in cell energy balance and in cell fate determination. Studies on the role of mitochondrial Ca(2+) signaling in pathophysiology have been favored by the identification of the genes encoding the mitochondrial calcium uniporter (MCU) and its regulatory subunits. Thus, research carried on in the last years on one hand has determined the structure of the MCU complex and its regulation, on the other has uncovered the consequences of dysregulated mitochondrial Ca(2+) signaling in cell and tissue homeostasis...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28732507/long-noncoding-rna-expression-profiles-in-sub-lethal-heat-treated-hepatoma-carcinoma-cells
#2
Qingsong Deng, Shihan Chen, Chunchuan Fu, Jiayun Jiang, Mengda Zou, Yunhua Tan, Xiaofei Wang, Feng Xia, Kai Feng, Kuansheng Ma, Ping Bie
BACKGROUND: Sub-lethal heat treatment characterizes a transition zone of radiofrequency ablation (RFA) which explains hepatocellular carcinoma (HCC) residual cancer occurrence in this area after RFA treatment. The biochemistry of residual cancer cell recurrence is poorly understood, but long noncoding RNAs (lncRNAs) may have aberrant expression that is associated with diverse cancers. Thus, we measured lncRNA gene expression in sub-lethally heat-treated HCC cells using microarray. METHOD: Differentially expressed lncRNA and mRNA were measured with an Agilent Human lncRNA + mRNA Array V4...
July 21, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28726639/mitochondrial-calcium-uniporter-in-drosophila-transfers-calcium-between-the-endoplasmic-reticulum-and-mitochondria-in-oxidative-stress-induced-cell-death
#3
Sekyu Choi, Xianglan Quan, Sunhoe Bang, Heesuk Yoo, Jiyoung Kim, Jiwon Park, Kyu-Sang Park, Jongkyeong Chung
Mitochondrial calcium plays critical roles in diverse cellular processes ranging from energy metabolism to cell death. Previous studies have demonstrated that mitochondrial calcium uptake is mainly mediated by the mitochondrial calcium uniporter (MCU) complex. However, the roles of the MCU complex in calcium transport, signaling, and dysregulation by oxidative stress still remain unclear. Here, we confirmed that Drosophila MCU contains evolutionarily conserved structures and requires essential MCU regulator (EMRE) for its calcium channel activities...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28725491/ds16570511-is-a-small-molecule-inhibitor-of-the-mitochondrial-calcium-uniporter
#4
Naohiro Kon, Michiko Murakoshi, Aya Isobe, Katsuji Kagechika, Naoki Miyoshi, Takahiro Nagayama
In cardiac myocytes, regulation of mitochondrial Ca(2+) is important for cellular signaling and cardiac contraction. Ca(2+) entry into the mitochondria is mediated by a highly selective Ca(2+) channel called the mitochondrial calcium uniporter, which consists of a pore-forming subunit MCU and regulatory subunits such as MICU1. Although pharmacological regulation of the mitochondrial Ca(2+) influx is a promising approach to controlling the cellular functions, a cell-permeable and specific inhibitor of the mitochondrial calcium uniporter has not yet been developed...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28698627/the-energy-disruptor-metformin-targets-mitochondrial-integrity-via-modification-of-calcium-flux-in-cancer-cells
#5
Camille Loubiere, Stephan Clavel, Jerome Gilleron, Rania Harisseh, Jeremy Fauconnier, Issam Ben-Sahra, Lisa Kaminski, Kathiane Laurent, Stephanie Herkenne, Sandra Lacas-Gervais, Damien Ambrosetti, Damien Alcor, Stephane Rocchi, Mireille Cormont, Jean-François Michiels, Bernard Mari, Nathalie M Mazure, Luca Scorrano, Alain Lacampagne, Abdallah Gharib, Jean-François Tanti, Frederic Bost
Mitochondrial integrity is critical for the regulation of cellular energy and apoptosis. Metformin is an energy disruptor targeting complex I of the respiratory chain. We demonstrate that metformin induces endoplasmic reticulum (ER) stress, calcium release from the ER and subsequent uptake of calcium into the mitochondria, thus leading to mitochondrial swelling. Metformin triggers the disorganization of the cristae and inner mitochondrial membrane in several cancer cells and tumors. Mechanistically, these alterations were found to be due to calcium entry into the mitochondria, because the swelling induced by metformin was reversed by the inhibition of mitochondrial calcium uniporter (MCU)...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28650465/mcu-dependent-mitochondrial-ca-2-inhibits-nad-sirt3-sod2-pathway-to-promote-ros-production-and-metastasis-of-hcc-cells
#6
T Ren, H Zhang, J Wang, J Zhu, M Jin, Y Wu, X Guo, L Ji, Q Huang, H Zhang, H Yang, J Xing
Mitochondrial Ca(2+) signaling, which is strongly dependent on the mitochondrial Ca(2+) uniporter (MCU) complex, has a series of key roles in physiopathological processes, including energy metabolism, reactive oxygen species (ROS) production and cell apoptosis. However, a mechanistic understanding of how the mitochondrial Ca(2+) signaling is remodeled and its functional roles remains greatly limited in cancers, especially in hepatocellular carcinoma. Here we demonstrated that the MCU complex was dysregulated in hepatocellular carcinoma (HCC) cells and significantly correlated with metastasis and poor prognosis of HCC patients...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28646724/zinc-and-calcium-alter-the-relationship-between-mitochondrial-respiration-ros-and-membrane-potential-in-rainbow-trout-oncorhynchus-mykiss-liver-mitochondria
#7
Mahmoud S Sharaf, Don Stevens, Collins Kamunde
At excess levels, zinc (Zn) disrupts mitochondrial functional integrity and induces oxidative stress in aquatic organisms. Although much is known about the modulation of Zn toxicity by calcium (Ca) in fish, their interactions at the mitochondrial level have scarcely been investigated. Here we assessed the individual and combined effects of Zn and Ca on the relationship between mitochondrial respiration, ROS and membrane potential (ΔΨmt) in rainbow trout liver mitochondria. We tested if cation uptake through the mitochondrial calcium uniporter (MCU) is a prerequisite for Zn- and/or Ca-induced alteration of mitochondrial function...
August 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28578342/astragaloside-iv-protects-against-heat-induced-apoptosis-by-inhibiting-excessive-activation-of-mitochondrial-ca2-uniporter
#8
Zhiwei Dong, Chen Zhang, Yajie Chen, Yu Chen, Zhiqiang Yuan, Yizhi Peng, Tongtong Cao
BACKGROUND: Heat causes airway damage during inhalation injury because of bronchial epithelial cell damage. Accumulating evidence shows that mitochondrial uniporter (MCU) is involved in cell damage. We investigated the MCU activity after heat treatment and assessed whether Astragaloside-IV (AS-IV) suppresses heat-induced apoptosis in bronchial epithelial cells by inhibiting the activation of the mitochondrial Ca2+ uniporter (MCU), mitochondrial depolarisation and reactive oxygen species (ROS) production...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28560396/mitochondrial-ca2-removal-amplifies-trail-cytotoxicity-toward-apoptosis-resistant-tumor-cells-via-promotion-of-multiple-cell-death-modalities
#9
Natsuhiko Takata, Yohei Ohshima, Miki Suzuki-Karasaki, Yukihiro Yoshida, Yasuaki Tokuhashi, Yoshihiro Suzuki-Karasaki
Ca2+ has emerged as a new target for cancer treatment since tumor-specific traits in Ca2+ dynamics contributes to tumorigenesis, malignant phenotypes, drug resistance, and survival in different tumor types. However, Ca2+ has a dual (pro-death and pro-survival) function in tumor cells depending on the experimental conditions. Therefore, it is necessary to minimize the onset of the pro-survival Ca2+ signals caused by the therapy. For this purpose, a better understanding of pro-survival Ca2+ pathways in cancer cells is critical...
May 25, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28495532/new-insights-into-the-role-of-mitochondrial-calcium-homeostasis-in-cell-migration
#10
Vincent Paupe, Julien Prudent
Mitochondria are dynamic organelles involved in numerous physiological functions. Beyond their function in ATP production, mitochondria regulate cell death, reactive oxygen species (ROS) generation, immunity and metabolism. Mitochondria also play a key role in the buffering of cytosolic calcium, and calcium transported into the matrix regulates mitochondrial metabolism. Recently, the identification of the mitochondrial calcium uniporter (MCU) and associated regulators has allowed the characterization of new physiological roles for calcium in both mitochondrial and cellular homeostasis...
May 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28487431/different-roles-of-mitochondrial-calcium-uniporter-complex-subunits-in-growth-and-infectivity-of-trypanosoma-cruzi
#11
Miguel A Chiurillo, Noelia Lander, Mayara S Bertolini, Melissa Storey, Anibal E Vercesi, Roberto Docampo
Trypanosoma cruzi is the agent of Chagas disease, and the finding that this parasite possesses a mitochondrial calcium uniporter (TcMCU) with characteristics similar to that of mammalian mitochondria was fundamental for the discovery of the molecular nature of MCU in eukaryotes. We report here that ablation of TcMCU, or its paralog TcMCUb, by clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 led to a marked decrease in mitochondrial Ca(2+) uptake without affecting the membrane potential of these cells, whereas overexpression of each gene caused a significant increase in the ability of mitochondria to accumulate Ca(2+) While TcMCU-knockout (KO) epimastigotes were viable and able to differentiate into trypomastigotes, infect host cells, and replicate normally, ablation of TcMCUb resulted in epimastigotes having an important growth defect, lower rates of respiration and metacyclogenesis, more pronounced autophagy changes under starvation, and significantly reduced infectivity...
May 9, 2017: MBio
https://www.readbyqxmd.com/read/28438761/improved-skeletal-muscle-ca-2-regulation-in-vivo-following-contractions-in-mice-overexpressing-pgc-1%C3%AE
#12
Hiroaki Eshima, Shinji Miura, Nanami Senoo, Koji Hatakeyama, David C Poole, Yutaka Kano
In skeletal muscle, resting intracellular Ca(2+) concentration ([Ca(2+)]i) homeostasis is exquisitely regulated by Ca(2+) transport across the sarcolemmal, mitochondrial and sarcoplasmic reticulum (SR) membranes. Of these three systems, the relative importance of the mitochondria in [Ca(2+)]i regulation remains poorly understood in in vivo skeletal muscle. We tested the hypothesis that the capacity for Ca(2+) uptake by mitochondria is a primary factor in determining [Ca(2+)]i regulation in muscle at rest and following contractions...
April 24, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28396416/proteolytic-control-of-the-mitochondrial-calcium-uniporter-complex
#13
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 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28394306/dynamic-synchronous-capture-algorithm-for-an-electromagnetic-flowmeter
#14
Yong-Yi Fanjiang, Shih-Wei Lu
This paper proposes a dynamic synchronous capture (DSC) algorithm to calculate the flow rate for an electromagnetic flowmeter. The characteristics of the DSC algorithm can accurately calculate the flow rate signal and efficiently convert an analog signal to upgrade the execution performance of a microcontroller unit (MCU). Furthermore, it can reduce interference from abnormal noise. It is extremely steady and independent of fluctuations in the flow measurement. Moreover, it can calculate the current flow rate signal immediately (m/s)...
April 10, 2017: Sensors
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
#15
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/28380201/study-of-the-kinematic-variables-of-unilateral-and-habitual-mastication-of-healthy-individuals
#16
Fernanda Pasinato, Andréia Gussi de Oliveira, Clarissa C Santos-Couto-Paz, Jorge Luis Lopes Zeredo, Geovana de Paula Bolzan, Sergio Bruzadelli Macedo, Eliane C R Corrêa
Purpose: To describe and compare the temporal-spatial kinematic variables of mandibular movement during deliberate unilateral and habitual mastication in healthy young-adult individuals. Methods: The study sample was composed of eight male healthy volunteers aged 19 to 24 years. The kinematic data were obtained using a motion analysis system - Qualisys Track Manager (QTM) ProReflex MCU. Recordings were performed during deliberate unilateral mastication (UM) and habitual mastication (HM) of firm-consistency gummy candy...
March 30, 2017: CoDAS
https://www.readbyqxmd.com/read/28351840/macrophages-utilize-the-mitochondrial-calcium-uniporter-for-profibrotic-polarization
#17
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...
July 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
#18
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
#19
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
#20
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
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