keyword
MENU ▼
Read by QxMD icon Read
search

Mitochondrial calcium uniporter

keyword
https://www.readbyqxmd.com/read/29323106/sequential-forward-and-reverse-transport-of-the-na-ca2-exchanger-generates-ca2-oscillations-within-mitochondria
#1
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
#2
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 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29286188/the-mitochondrial-calcium-uniporter-complex-in-trypanosomes
#3
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-ca2-transport-in-the-endothelium-regulation-by-ions-redox-signalling-and-mechanical-forces
#4
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
#5
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...
December 7, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29210126/crosslink-of-calcium-and-sodium-signalling-in-health-and-disease
#6
Alexei Verkhratsky, Mohamed Trebak, Fabiana Perocchi, Daniel Khananishvili, Israel Sekler
Transmembrane ionic gradients, that are indispensable feature of life, are utilised for generation of cytosolic ionic signals that regulate a host of cellular functions. Intracellular signalling mediated by Ca2+ and Na+ is tightly linked through several molecular pathways that generate Ca2+ and Na+ fluxes and are in turn regulated by both ions. Transient receptor potential (TRP) channels bridge endoplasmic reticulum Ca2+ release with generation of Na+ and Ca2+ currents. Plasmalemmal Na+ /Ca2+ exchanger by flickering between forward and reverse mode coordinates influx and efflux of both ions with membrane polarisation and cytosolic ion concentration...
December 6, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29142021/inf2-mediated-actin-polymerization-at-the-er-stimulates-mitochondrial-calcium-uptake-inner-membrane-constriction-and-division
#7
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...
November 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29137386/mitochondrial-calcium-uniporter-as-a-target-of-microrna-340-and-promoter-of-metastasis-via-enhancing-the-warburg-effect
#8
Changhui Yu, Yuhao Wang, Jiawen Peng, Qiang Shen, Mimi Chen, Wei Tang, Xiumei Li, Chunqing Cai, Bin Wang, Shaoxi Cai, Xiaojing Meng, Fei Zou
Background: A shift from oxygen phosphorylation to aerobic glycolysis was known as the Warburg effect and a characteristic of cancer cell metabolism facilitating metastasis. Mitochondrial calcium uniporter (MCU), a key ion channel that mediates Ca(2+) uptake into mitochondria, was found to promote cancer progression and metastasis. However, its explicit role in shifting metabolism of breast cancer cells has not been defined. Methods: We evaluated MCU overexpression or knock-down on migration, invasion and glucose metabolismin breast cancer cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29073106/cardiovascular-homeostasis-dependence-on-micu2-a-regulatory-subunit-of-the-mitochondrial-calcium-uniporter
#9
Alexander G Bick, Hiroko Wakimoto, Kimberli J Kamer, Yasemin Sancak, Olga Goldberger, Anna Axelsson, Daniel M DeLaughter, Joshua M Gorham, Vamsi K Mootha, J G Seidman, Christine E Seidman
Comparative analyses of transcriptional profiles from humans and mice with cardiovascular pathologies revealed consistently elevated expression of MICU2, a regulatory subunit of the mitochondrial calcium uniporter complex. To determine if MICU2 expression was cardioprotective, we produced and characterized Micu2-/- mice. Mutant mice had left atrial enlargement and Micu2-/- cardiomyocytes had delayed sarcomere relaxation and cytosolic calcium reuptake kinetics, indicating diastolic dysfunction. RNA sequencing (RNA-seq) of Micu2-/- ventricular tissues revealed markedly reduced transcripts encoding the apelin receptor (Micu2-/- vs...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073097/content-of-mitochondrial-calcium-uniporter-mcu-in-cardiomyocytes-is-regulated-by-microrna-1-in-physiologic-and-pathologic-hypertrophy
#10
Tania Zaglia, Paola Ceriotti, Antonio Campo, Giulia Borile, Andrea Armani, Pierluigi Carullo, Valentina Prando, Raffaele Coppini, Vladimiro Vida, Tomas O Stølen, Wisløff Ulrik, Elisabetta Cerbai, Giovanni Stellin, Giuseppe Faggian, Diego De Stefani, Marco Sandri, Rosario Rizzuto, Fabio Di Lisa, Tullio Pozzan, Daniele Catalucci, Marco Mongillo
The mitochondrial Ca(2+) uniporter complex (MCUC) is a multimeric ion channel which, by tuning Ca(2+) influx into the mitochondrial matrix, finely regulates metabolic energy production. In the heart, this dynamic control of mitochondrial Ca(2+) uptake is fundamental for cardiomyocytes to adapt to either physiologic or pathologic stresses. Mitochondrial calcium uniporter (MCU), which is the core channel subunit of MCUC, has been shown to play a critical role in the response to β-adrenoreceptor stimulation occurring during acute exercise...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29053821/a-null-mutation-in-micu2-causes-abnormal-mitochondrial-calcium-homeostasis-and-a-severe-neurodevelopmental-disorder
#11
Hanan E Shamseldin, Ali Alasmari, Mohammed A Salih, Manar M Samman, Shahid A Mian, Tarfa Alshidi, Niema Ibrahim, Mais Hashem, Eissa Faqeih, Futwan Al-Mohanna, Fowzan S Alkuraya
Mitochondrial calcium homeostasis is a tightly controlled process that is required for a variety of cellular functions. The mitochondrial calcium uniporter complex plays a critical role in this process. MICU2 is a major component of the mitochondrial calcium uniporter complex and its deficiency has been shown to impair mitochondrial calcium [Ca2+]m homeostasis although the exact mechanism remains unclear. We used exome sequencing, positional mapping, and functional characterization of MICU2 deficiency to investigate the role of MICU2 in calcium homeostasis...
November 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29047093/cross-talk-between-mitochondrial-reactive-oxygen-species-and-sarcoplasmic-reticulum-calcium-in-pulmonary-arterial-smooth-muscle-cells
#12
Tengyao Song, Yun-Min Zheng, Yong-Xiao Wang
Hypoxic pulmonary vasoconstriction (HPV) occurs during both fetal and postnatal development and plays a critical role in matching regional alveolar perfusion with ventilation in humans and animals. HPV also contributes significantly to the development of pulmonary hypertension. Although the molecular mechanisms of HPV and pulmonary hypertension remain incompletely understood, increasing evidence demonstrates that hypoxia induces an elevated intracellular reactive oxygen species concentration ([ROS]i) in pulmonary artery smooth muscle cells (PASMCs)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29038245/mitochondrial-calcium-dysregulation-contributes-to-dendrite-degeneration-mediated-by-pd-lbd-associated-lrrk2-mutants
#13
Manish Verma, Jason Callio, P Anthony Otero, Israel Sekler, Zachary P Wills, Charleen T Chu
Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of late-onset familial Parkinson's disease (PD), with clinical features of motor and cognitive dysfunction indistinguishable from sporadic PD. Calcium dysregulation plays an important role in PD pathogenesis, but the mechanisms of neurodegeneration remain unclear. Recent reports indicate enhanced excitatory neurotransmission in cortical neurons expressing mutant LRRK2, which occurs prior to the well-characterized phenotype of dendritic shortening...
October 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28990420/synaptic-activity-protects-neurons-against-calcium-mediated-oxidation-and-contraction-of-mitochondria-during-excitotoxicity
#14
Constanze Depp, Carlos Bas-Orth, Lisa Schroeder, Andrea Hellwig, Hilmar Bading
AIMS: Excitotoxicity triggered by extrasynaptic N-methyl-d-aspartate-type glutamate receptors has been implicated in many neurodegenerative conditions, including Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke. Mitochondrial calcium overload leading to mitochondrial dysfunction represents an early event in excitotoxicity. Neurons are rendered resistant to excitotoxicity by previous periods of synaptic activity that activates a nuclear calcium-driven neuroprotective gene program...
November 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28962857/mitochondrial-cardiomyopathies-feature-increased-uptake-and-diminished-efflux-of-mitochondrial-calcium
#15
Salah Sommakia, Patrick R Houlihan, Sadiki S Deane, Judith A Simcox, Natalia S Torres, Mi-Young Jeong, Dennis R Winge, Claudio J Villanueva, Dipayan Chaudhuri
Calcium (Ca(2+)) influx into the mitochondrial matrix stimulates ATP synthesis. Here, we investigate whether mitochondrial Ca(2+) transport pathways are altered in the setting of deficient mitochondrial energy synthesis, as increased matrix Ca(2+) may provide a stimulatory boost. We focused on mitochondrial cardiomyopathies, which feature such dysfunction of oxidative phosphorylation. We study a mouse model where the main transcription factor for mitochondrial DNA (transcription factor A, mitochondrial, Tfam) has been disrupted selectively in cardiomyocytes...
December 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28947137/hint2-triggers-mitochondrial-ca-2-influx-by-regulating-the-mitochondrial-ca-2-uniporter-mcu-complex-and-enhances-gemcitabine-apoptotic-effect-in-pancreatic-cancer
#16
Linghui Chen, Qiang Sun, Dongkai Zhou, Wei Song, Qifan Yang, Bingjie Ju, Lufei Zhang, Haiyang Xie, Lin Zhou, Zhenhua Hu, Hangping Yao, Shusen Zheng, Weilin Wang
In early studies, it was shown that HINT2, which sensitizes cells to mitochondrial apoptosis, is down-regulated in hepatocellular carcinoma (HCC) cells (Martin et al., 2006). However, the molecular mechanism of this effect is unknown. Immunohistochemistry revealed that HINT2 expression is relatively low in pancreatic cancer tissues, compared to that in adjacent tissues (P < 0.05). Furthermore, its expression was related to pathological grade and lymph node metastasis (P = 0.0161 and 0.0108, respectively); in addition, down-regulation of HINT2 was found to be associated with relatively poor prognosis in pancreatic cancer patients...
September 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28944215/endoplasmic-reticulum-mitochondria-calcium-communication-and-the-regulation-of-mitochondrial-metabolism-in-cancer-a-novel-potential-target
#17
REVIEW
Galdo Bustos, Pablo Cruz, Alenka Lovy, César Cárdenas
Cancer is characterized by an uncontrolled cell proliferation rate even under low nutrient availability, which is sustained by a metabolic reprograming now recognized as a hallmark of cancer. Warburg was the first to establish the relationship between cancer and mitochondria; however, he interpreted enhanced aerobic glycolysis as mitochondrial dysfunction. Today it is accepted that many cancer cell types need fully functional mitochondria to maintain their homeostasis. Calcium (Ca(2+))-a key regulator of several cellular processes-has proven to be essential for mitochondrial metabolism...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28942921/mitochondrial-fission-promotes-the-continued-clearance-of-apoptotic-cells-by-macrophages
#18
Ying Wang, Manikandan Subramanian, Arif Yurdagul, Valéria C Barbosa-Lorenzi, Bishuang Cai, Jaime de Juan-Sanz, Timothy A Ryan, Masatoshi Nomura, Frederick R Maxfield, Ira Tabas
Clearance of apoptotic cells (ACs) by phagocytes (efferocytosis) prevents post-apoptotic necrosis and dampens inflammation. Defective efferocytosis drives important diseases, including atherosclerosis. For efficient efferocytosis, phagocytes must be able to internalize multiple ACs. We show here that uptake of multiple ACs by macrophages requires dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, which is triggered by AC uptake. When mitochondrial fission is disabled, AC-induced increase in cytosolic calcium is blunted owing to mitochondrial calcium sequestration, and calcium-dependent phagosome formation around secondarily encountered ACs is impaired...
October 5, 2017: Cell
https://www.readbyqxmd.com/read/28939404/inhibition-of-the-mitochondrial-calcium-uniporter-inhibits-a%C3%AE-induced-apoptosis-by-reducing-reactive-oxygen-species-mediated-endoplasmic-reticulum-stress-in-cultured-microglia
#19
Nanchang Xie, Chuanjie Wu, Cui Wang, Xuan Cheng, Lu Zhang, Haifeng Zhang, Yajun Lian
Amyloid-beta (Aβ) has been shown to induce microglial apoptosis, which is itself sensitive to disturbed mitochondrial calcium (Ca(2+)) homeostasis. The mitochondrial calcium uniporter (MCU) plays an important regulatory role in mitochondrial Ca(2+) homeostasis, but its role in Aβ-induced microglia apoptosis is unknown. In this study, we found increased mitochondrial Ca(2+) concentration in Aβ-treated primary microglia and BV-2 cells; also, the MCU inhibitor Ru360 significantly attenuated Aβ-induced microglial apoptosis, whereas the MCU activator spermine augmented it...
December 1, 2017: Brain Research
https://www.readbyqxmd.com/read/28938844/mcur1-mediated-mitochondrial-calcium-signaling-facilitates-cell-survival-of-hepatocellular-carcinoma-via-reactive-oxygen-species-dependent-p53-degradation
#20
Tingting Ren, Jiaojiao Wang, Hui Zhang, Peng Yuan, Jianjun Zhu, Yousheng Wu, Qichao Huang, Xu Guo, Jing Zhang, Lele Ji, Jibin Li, Hongxin Zhang, Hushan Yang, Jinliang Xing
AIMS: Levels of the mitochondrial calcium uniporter regulator 1 (MCUR1) increases during development of hepatocellular carcinoma (HCC). However, mechanisms of how mitochondrial Ca(2+) homeostasis is modulated and its function remain limited in cancers. RESULTS: MCUR1 was frequently upregulated in HCC cells to enhance the Ca(2+) uptake into mitochondria in an MCU-dependent manner, which significantly facilitated cell survival by inhibiting mitochondria-dependent intrinsic apoptosis and promoting proliferation of HCC cells, and thus led to poor prognosis...
November 1, 2017: Antioxidants & Redox Signaling
keyword
keyword
35468
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"