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Mitochondrial calcium uniporter

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https://www.readbyqxmd.com/read/29789575/tamoxifen-induced-knockdown-of-the-mitochondrial-calcium-uniporter-in-thy1-expressing-neurons-protects-mice-from-hypoxic-ischemic-brain-injury
#1
Matthew Nichols, Evgeny V Pavlov, George S Robertson
The mitochondrial calcium uniporter (MCU) mediates high-capacity mitochondrial calcium uptake that stimulates energy production. However, excessive MCU activity can cause ischemic heart injury. To examine if the MCU is also involved in hypoxic/ischemic (HI) brain injury, we have generated conditional MCU knockout mice by tamoxifen (TMX) administration to adult MCU-floxed (MCUfl/fl ) mice expressing a construct encoding Thy1-cre/ERT2-eYFP. Relative to TMX/Thy1-cre/ERT2-eYFP controls, HI-induced sensorimotor deficits, forebrain neuron loss and mitochondrial damage were decreased for conditional MCU knockout mice...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748369/calcium-signaling-and-reactive-oxygen-species-in-mitochondria
#2
REVIEW
Edoardo Bertero, Christoph Maack
In heart failure, alterations of Na+ and Ca2+ handling, energetic deficit, and oxidative stress in cardiac myocytes are important pathophysiological hallmarks. Mitochondria are central to these processes because they are the main source for ATP, but also reactive oxygen species (ROS), and their function is critically controlled by Ca2+ During physiological variations of workload, mitochondrial Ca2+ uptake is required to match energy supply to demand but also to keep the antioxidative capacity in a reduced state to prevent excessive emission of ROS...
May 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29721912/a-middle-eastern-founder-mutation-expands-the-genotypic-and-phenotypic-spectrum-of-mitochondrial-micu1-deficiency-a-report-of-13-patients
#3
Sara Musa, Wafaa Eyaid, Kimberli Kamer, Rehab Ali, Mariam Al-Mureikhi, Noora Shahbeck, Fatma Al Mesaifri, Nawal Makhseed, Zakkiriah Mohamed, Wafaa Ali AlShehhi, Vamsi K Mootha, Jane Juusola, Tawfeg Ben-Omran
MICU1 encodes a Ca2+ sensing, regulatory subunit of the mitochondrial uniporter, a selective calcium channel within the organelle's inner membrane. Ca2+ entry into mitochondria helps to buffer cytosolic Ca2+ transients and also activates ATP production within the organelle. Mutations in MICU1 have previously been reported in 17 children from nine families with muscle weakness, fatigue, normal lactate, and persistently elevated creatine kinase, as well as variable features that include progressive extrapyramidal signs, learning disabilities, nystagmus, and cataracts...
May 3, 2018: JIMD Reports
https://www.readbyqxmd.com/read/29701876/arabidopsis-pollen-tube-germination-and-growth-depend-on-the-mitochondrial-calcium-uniporter-complex
#4
Benjamin Selles, Caroline Michaud, Tou-Cheu Xiong, Olivier Leblanc, Mathieu Ingouff
The mitochondrial calcium uniporter complex (MCUc) was recently characterized in details in metazoans and consists of pore-forming units (MCUs) and regulatory factors that channel calcium (Ca2+ ) ion into the mitochondria. MCUs participate in many stress and developmentally related processes involving Ca2+ . Although multiple homologues of MCUs and one regulatory subunit are usually present in plants, the first functional characterization and contribution to Ca2+ related processes of these proteins have been reported recently...
April 27, 2018: New Phytologist
https://www.readbyqxmd.com/read/29695246/transcriptomic-analysis-between-self-and-cross-pollinated-pistils-of-tea-plants-camellia-sinensis
#5
Qingping Ma, Changsong Chen, Zhongping Zeng, Zhongwei Zou, Huan Li, Qiongqiong Zhou, Xuan Chen, Kang Sun, Xinghui Li
BACKGROUND: Self-incompatibility (SI) is a major barrier that obstructs the breeding process in most horticultural plants including tea plants (Camellia sinensis). The aim of this study was to elucidate the molecular mechanism of SI in tea plants through a high throughput transcriptome analysis. RESULTS: In this study, the transcriptomes of self- and cross-pollinated pistils of two tea cultivars 'Fudingdabai' and 'Yulv' were compared to elucidate the SI mechanism of tea plants...
April 25, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29686046/mcu-interacts-with-miro1-to-modulate-mitochondrial-functions-in-neurons
#6
Robert F Niescier, Kido Hong, Dongkeun Park, Kyung-Tai Min
Mitochondrial Ca2+ uptake is gated by the mitochondrial calcium uniplex, which is comprised of MCU, the Ca2+ pore-forming subunit of the complex, and its regulators. Ca2+ influx through MCU affects both mitochondrial function and movement in neurons, but its direct role in mitochondrial movement has not been explored. In this report, we show a link between MCU and Miro1, a membrane protein known to regulate mitochondrial movement. We find that MCU interacts with Miro1 through MCU's N-terminal domain, previously thought to be the mitochondrial targeting sequence...
April 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29626093/restoring-mitochondrial-calcium-uniporter-expression-in-diabetic-mouse-heart-improves-mitochondrial-calcium-handling-and-cardiac-function
#7
Jorge Suarez, Federico Cividini, Brian T Scott, Kim Lehmann, Julieta Diaz-Juarez, Tanja Diemer, Anzhi Dai, Jorge A Suarez, Mohit Jain, Wolfgang H Dillmann
Diabetes mellitus is a growing health care problem, resulting in significant cardiovascular morbidity and mortality. Diabetes also increases the risk for heart failure (HF) and decreased cardiac myocyte function, which are linked to changes in cardiac mitochondrial energy metabolism. The free mitochondrial calcium level ([Ca2+]m) is fundamental in activating the mitochondrial respiratory chain complexes and ATP production and is also known to regulate pyruvate dehydrogenase complex (PDC) activity. The mitochondrial calcium uniporter (MCU) complex (MCUC) plays a major role in mediating mitochondrial Ca2+ import, and its expression and function therefore have a marked impact on cardiac myocyte metabolism and function...
April 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29594529/ferutinin-induces-membrane-depolarization-permeability-transition-pore-formation-and-respiration-uncoupling-in-isolated-rat-liver-mitochondria-by-stimulation-of-ca-2-permeability
#8
Tatsiana Ilyich, Oksana Charishnikova, Szymon Sekowski, Maria Zamaraeva, Vitali Cheshchevik, Iosif Dremza, Nina Cheshchevik, Lyudmila Kiryukhina, Elena Lapshina, Ilya Zavodnik
It is well known that the terpenoid ferutinin (4-oxy-6-(4-oxybenzoyloxy) dauc-8,9-en), isolated from the plant Ferula tenuisecta, considerably increases the permeability of artificial and cellular membranes to Ca2+ -ions and produces apoptotic cell death in different cell lines in a mitochondria-dependent manner. The present study was designed for further evaluation of the mechanism(s) of mitochondrial effects of ferutinin using isolated rat liver mitochondria. Our findings provide evidence for ferutinin at concentrations of 5-27 µM to decrease state 3 respiration and the acceptor control ratio in the case of glutamate/malate as substrates...
March 28, 2018: Journal of Membrane Biology
https://www.readbyqxmd.com/read/29549313/astrocytic-metabolic-switch-is-a-novel-etiology-for-cocaine-and-hiv-1-tat-mediated-neurotoxicity
#9
Kalimuthusamy Natarajaseenivasan, Bianca Cotto, Santhanam Shanmughapriya, Alyssa A Lombardi, Prasun K Datta, Muniswamy Madesh, John W Elrod, Kamel Khalili, Dianne Langford
Calcium (Ca2+ ) dynamics and oxidative signaling control mitochondrial bioenergetics in the central nervous system, where astrocytes are a major energy source for neurons. Cocaine use exacerbates HIV-associated neurocognitive disorders, but little is known about disruptions in astrocyte metabolism in this context. Our data show that the HIV protein Tat and cocaine induce a metabolic switch from glucose to fatty acid oxidation in astrocytes, thereby limiting lactate transport to neurons. Mechanistic analyses revealed increased Mitochondrial Ca2+ Uniporter (MCU)-mediated Ca2+ uptake in astrocytes exposed to Tat and cocaine due to oxidation of MCU...
March 16, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29541860/mitochondrial-calcium-uptake-in-organ-physiology-from-molecular-mechanism-to-animal-models
#10
REVIEW
Cristina Mammucari, Anna Raffaello, Denis Vecellio Reane, Gaia Gherardi, Agnese De Mario, Rosario Rizzuto
Mitochondrial Ca2+ is involved in heterogeneous functions, ranging from the control of metabolism and ATP production to the regulation of cell death. In addition, mitochondrial Ca2+ uptake contributes to cytosolic [Ca2+ ] shaping thus impinging on specific Ca2+ -dependent events. Mitochondrial Ca2+ concentration is controlled by influx and efflux pathways: the former controlled by the activity of the mitochondrial Ca2+ uniporter (MCU), the latter by the Na+ /Ca2+ exchanger (NCLX) and the H+ /Ca2+ (mHCX) exchanger...
March 15, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29538099/mitochondrial-calcium-uniporter-mediated-inhibition-of-1-methyl-4-phenylpyridinium-ions-neurotoxicity-in-pc12-cells
#11
Huiling Wang, Menglan Zhao, Jialong Chen, Yixian Ren, Guanghai Wang, Wenjun Li, Fei Zou
Parkinson's disease (PD) is one of the most debilitating neurodegenerative disorders. The etiology of sporadic PD remains unknown. One prominent hypothesis is that impaired mitochondrial function may underlie slow and progressive neurodegeneration. Mitochondrial calcium uniporter (MCU) is a crucial component that regulates the intramitochondrial Ca level. Ca uptake to the mitochondria by MCU, resulting in activation of mitochondrial dehydrogenases and stimulation of ATP synthesis, but excessive Ca uptake to the mitochondria resulting in cell apoptosis...
May 2, 2018: Neuroreport
https://www.readbyqxmd.com/read/29531827/-mycobacterium-fortuitum-induced-er-mitochondrial-calcium-dynamics-promotes-calpain-caspase-12-caspase-9-mediated-apoptosis-in-fish-macrophages
#12
Debika Datta, Preeti Khatri, Ambika Singh, Dhira Rani Saha, Gaurav Verma, Rajagopal Raman, Shibnath Mazumder
Mycobacterium fortuitum is a natural fish pathogen. It induces apoptosis in headkidney macrophages (HKM) of catfish, Clarias sp though the mechanism remains largely unknown. We observed M. fortuitum triggers calcium (Ca2+ ) insult in the sub-cellular compartments which elicits pro-apototic ER-stress factor CHOP. Alleviating ER-stress inhibited CHOP and attenuated HKM apoptosis implicating ER-stress in the pathogenesis of M. fortuitum . ER-stress promoted calpain activation and silencing the protease inhibited caspase-12 activation...
December 2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29451229/m-aaa-proteases-mitochondrial-calcium-homeostasis-and-neurodegeneration
#13
REVIEW
Maria Patron, Hans-Georg Sprenger, Thomas Langer
The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected...
March 2018: Cell Research
https://www.readbyqxmd.com/read/29323106/sequential-forward-and-reverse-transport-of-the-na-ca-2-exchanger-generates-ca-2-oscillations-within-mitochondria
#14
Krishna Samanta, Gary R Mirams, Anant B Parekh
Mitochondrial Ca2+ homoeostasis regulates aerobic metabolism and cell survival. Ca2+ flux into mitochondria is mediated by the mitochondrial calcium uniporter (MCU) channel whereas Ca2+ export is often through an electrogenic Na+ -Ca2+ exchanger. Here, we report remarkable functional versatility in mitochondrial Na+ -Ca2+ exchange under conditions where mitochondria are depolarised. Following physiological stimulation of cell-surface receptors, mitochondrial Na+ -Ca2+ exchange initially operates in reverse mode, transporting cytosolic Ca2+ into the matrix...
January 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29307826/single-channel-recording-of-a-mitochondrial-calcium-uniporter
#15
Guangyan Wu, Shunjin Li, Guangning Zong, Xiaofen Liu, Shuang Fei, Linda Shen, Xiangchen Guan, Xue Yang, Yuequan Shen
Mitochondrial calcium uniporter (MCU) is the pore-forming subunit of the entire uniporter complex and plays an important role in mitochondrial calcium uptake. However, the single channel recording of MCU remains controversial. Here, we expressed and purified different MCU proteins and then reconstituted them into planar lipid bilayers for single channel recording. We showed that MCU alone from Pyronema omphalodes (pMCU) is active with prominent single channel Ca2+ currents. In sharp contrast, MCU alone from Homo sapiens (hMCU) is inactive...
January 29, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29286188/the-mitochondrial-calcium-uniporter-complex-in-trypanosomes
#16
REVIEW
Noelia Lander, Miguel A Chiurillo, Mayara S Bertolini, Roberto Docampo, Aníbal E Vercesi
The presence of a conserved mechanism for mitochondrial calcium uptake in trypanosomatids was crucial for the molecular identification of the mitochondrial calcium uniporter (MCU), a long-sought channel present in most eukaryotic organisms. Since then, research efforts to elucidate the role of MCU and its regulatory elements in different biological models have multiplied. MCU is the pore-forming subunit of a multimeric complex (the MCU complex or MCUC) and its predicted structure in trypanosomes is simpler than in mammalian cells, lacking two of its subunits and probably possessing other unidentified components...
December 29, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29237825/mitochondrial-ca-2-transport-in-the-endothelium-regulation-by-ions-redox-signalling-and-mechanical-forces
#17
REVIEW
B Rita Alevriadou, Santhanam Shanmughapriya, Akshar Patel, Peter B Stathopulos, Muniswamy Madesh
Calcium (Ca2+ ) transport by mitochondria is an important component of the cell Ca2+ homeostasis machinery in metazoans. Ca2+ uptake by mitochondria is a major determinant of bioenergetics and cell fate. Mitochondrial Ca2+ uptake occurs via the mitochondrial Ca2+ uniporter (MCU) complex, an inner mitochondrial membrane protein assembly consisting of the MCU Ca2+ channel, as its core component, and the MCU complex regulatory/auxiliary proteins. In this review, we summarize the current knowledge on the molecular nature of the MCU complex and its regulation by intra- and extramitochondrial levels of divalent ions and reactive oxygen species (ROS)...
December 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29225050/inhibition-of-the-mitochondrial-calcium-uniporter-prevents-il-13-and-allergen-mediated-airway-epithelial-apoptosis-and-loss-of-barrier-function
#18
Sara C Sebag, Olha M Koval, John D Paschke, Christopher J Winters, Alejandro P Comellas, Isabella M Grumbach
Mitochondria are increasingly recognized as key mediators of acute cellular stress responses in asthma. However, the distinct roles of regulators of mitochondrial physiology on allergic asthma phenotypes are currently unknown. The mitochondrial Ca2+ uniporter (MCU) resides in the inner mitochondrial membrane and controls mitochondrial Ca2+ uptake into the mitochondrial matrix. To understand the function of MCU in models of allergic asthma, in vitro and in vivo studies were performed using models of functional deficiency or knockout of MCU...
January 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29210126/crosslink-between-calcium-and-sodium-signalling
#19
REVIEW
Alexei Verkhratsky, Mohamed Trebak, Fabiana Perocchi, Daniel Khananshvili, Israel Sekler
NEW FINDINGS: What is the topic of this review? This paper overviews the links between Ca2+ and Na+ signalling in various types of cells. What advances does it highlight? This paper highlights the general importance of ionic signalling and overviews the molecular mechanisms linking Na+ and Ca2+ dynamics. In particular, the narrative focuses on the molecular physiology of plasmalemmal and mitochondrial Na+ -Ca2+ exchangers and plasmalemmal transient receptor potential channels. Functional consequences of Ca2+ and Na+ signalling for co-ordination of neuronal activity with astroglial homeostatic pathways fundamental for synaptic transmission are discussed...
February 1, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29142021/inf2-mediated-actin-polymerization-at-the-er-stimulates-mitochondrial-calcium-uptake-inner-membrane-constriction-and-division
#20
Rajarshi Chakrabarti, Wei-Ke Ji, Radu V Stan, Jaime de Juan Sanz, Timothy A Ryan, Henry N Higgs
Mitochondrial division requires division of both the inner and outer mitochondrial membranes (IMM and OMM, respectively). Interaction with endoplasmic reticulum (ER) promotes OMM division by recruitment of the dynamin Drp1, but effects on IMM division are not well characterized. We previously showed that actin polymerization through ER-bound inverted formin 2 (INF2) stimulates Drp1 recruitment in mammalian cells. Here, we show that INF2-mediated actin polymerization stimulates a second mitochondrial response independent of Drp1: a rise in mitochondrial matrix calcium through the mitochondrial calcium uniporter...
January 2, 2018: Journal of Cell Biology
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