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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
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...
March 13, 2018: Neuroreport
Fanxin Zeng, Xiao Chen, Weiyi Cui, Wei Wen, Fujian Lu, Xueting Sun, Dongwei Ma, Ye Yuan, Zezhong Li, Ning Hou, Hong Zhao, Xinyu Bi, Jianjun Zhao, Jianguo Zhou, Yan Zhang, Rui-Ping Xiao, Jianqiang Cai, Xiuqin Zhang
The receptor-interacting protein kinase 1 (RIPK1) is an essential signaling molecule in pathways for cell survival, apoptosis, and necroptosis. We report here that RIPK1 is upregulated in human colorectal cancer (CRC) and promotes cell proliferation when overexpressed in a colon cancer cell line. RIPK1 interacts with mitochondrial Ca2+ uniporter (MCU) to promote proliferation by increasing mitochondrial Ca2+ uptake and energy metabolism. The ubiquitination site of RIPK1 (RIPK1-K377) was critical for this interaction with MCU and function in promoting cell proliferation...
March 12, 2018: Cancer Research
Bin Yu, Xinguang Chen, Yan Wang
BACKGROUND: Marijuana and tobacco are considered two closely related substances. It is of great significance to understand the mutual impact of marijuana and cigarette use when more states in the US have legalized marijuana use. OBJECTIVE: This study aims to investigate the transitions between marijuana and cigarette use among adolescents and emerging adults. METHOD: Guided by the probabilistic discrete events systems (PDES) theory, a five-stage model with 21 transition paths was constructed to quantify dynamic transitions between marijuana and cigarette use...
March 7, 2018: American Journal of Drug and Alcohol Abuse
Jonathan M Matthews, Andrea Fanelli, Thomas Heldt
OBJECTIVE: The monitoring of intracranial pressure (ICP) is indicated for diagnosing and guiding therapy in many neurological conditions. Current monitoring methods, however, are highly invasive, limiting their use to the most critically ill patients only. Our goal is to develop and test an embedded device that performs all necessary mathematical operations in real-time for noninvasive ICP (nICP) estimation based on a previously developed model-based approach that uses cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP) waveforms...
2018: Acta Neurochirurgica. Supplement
Edgar Djaha Yoboue, Roberto Sitia, Thomas Simmen
Many cellular redox reactions housed within mitochondria, peroxisomes and the endoplasmic reticulum (ER) generate hydrogen peroxide (H2 O2 ) and other reactive oxygen species (ROS). The contribution of each organelle to the total cellular ROS production is considerable, but varies between cell types and also over time. Redox-regulatory enzymes are thought to assemble at a "redox triangle" formed by mitochondria, peroxisomes and the ER, assembling "redoxosomes" that sense ROS accumulations and redox imbalances...
February 28, 2018: Cell Death & Disease
A L Gilmore-Bykovskyi, N Rogus-Pulia
OBJECTIVES: Dysphagia, or impaired swallowing, is common in nursing home (NH) residents with dementia and contributes to malnutrition and diminished quality of life. Dysphagia also commonly leads to aspiration or passage of food or fluids into the airway, which can result in aspiration pneumonia-a leading cause of death for people with dementia. Currently available interventions for dysphagia aim to modify the risk of aspiration events primarily by modifying diet and positioning to improve the safety of an individual's swallow...
2018: Journal of Nutrition, Health & Aging
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...
February 16, 2018: Cell Research
Aizhu Lu, Lei Hongyi, Le Li, Luying Lai, Wenbin Liang, Shiyuan Xu
Opioid-induced hyperalgesia and allodynia (OIH) is a well-known phenomenon and refers to the pain sensitization in patients after prolonged opioid exposure. OIH limits the use of opioids in pain control, but the underlying mechanisms are not fully clear. The present study investigated the role of mitochondrial Ca2+ uniporter (MCU) in remifentanil (a commonly used opioid analgesic)-induced allodynia. Using a rat model of OIH, we found that incision- and remifentanil-induced mechanical allodynia were remarkably attenuated by pretreatment with Ru360, a specific MCU antagonist, suggesting a critical role of MCU in both incision- and opioid-induced allodynia...
January 24, 2018: European Journal of Neuroscience
Maria K Schweitzer, Fabiola Wilting, Simon Sedej, Lisa Dreizehnter, Nathan J Dupper, Qinghai Tian, Alessandra Moretti, Ilaria My, Ohyun Kwon, Silvia G Priori, Karl-Ludwig Laugwitz, Ursula Storch, Peter Lipp, Andreas Breit, Michael Mederos Y Schnitzler, Thomas Gudermann, Johann Schredelseker
Cardiovascular disease-related deaths frequently arise from arrhythmias, but treatment options are limited due to perilous side effects of commonly used antiarrhythmic drugs. Cardiac rhythmicity strongly depends on cardiomyocyte Ca2+ handling and prevalent cardiac diseases are causally associated with perturbations in intracellular Ca2+ handling. Therefore, intracellular Ca2+ transporters are lead candidate structures for novel and safer antiarrhythmic therapies. Mitochondria and mitochondrial Ca2+ transport proteins are important regulators of cardiac Ca2+ handling...
December 2017: JACC. Basic to Translational Science
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
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
Riley Payne, Henry Hoff, Anne Roskowski, J Kevin Foskett
Ca2+ entry into mitochondria is mediated by the Ca2+ uniporter-channel complex containing MCU, the Ca2+-selective pore, and associated regulatory proteins. The roles of MICU proteins are controversial. MICU1 was proposed to be necessary for MCU activity, whereas subsequent studies suggested it inhibits the channel in the low-cytoplasmic Ca2+ ([Ca2+]c) regime, a mechanism referred to as "gatekeeping," that imposes a [Ca2+]c threshold for channel activation at ∼1-3 μM. Here, we measured MCU activity over a wide range of quantitatively controlled and recorded [Ca2+]c...
December 12, 2017: Cell Reports
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
Jing Yang, Alessandro Piai, Hong-Bin Shen, James J Chou
Nuclear magnetic resonance (NMR) has been an important source of structural restraints for solving structures of oligomeric transmembrane domains (TMDs) of cell surface receptors and viral membrane proteins. In NMR studies, oligomers are assembled using inter-protomer distance restraints. But, for oligomers that are higher than dimer, these distance restraints all have two-fold directional ambiguity, and resolving such ambiguity often requires time-consuming trial-and-error calculations using restrained molecular dynamics (MD) with simulated annealing (SA)...
December 12, 2017: Scientific Reports
Shuangxi Zhou, Wei Sheng, Fangming Deng, Xiang Wu, Zhihui Fu
In this paper, a novel approach for concrete chloride ion concentration measuring based on passive and wireless sensor tag is proposed. The chloride ion sensor based on RFID communication protocol is consisting of an energy harvesting and management circuit, a low dropout voltage regulator, a MCU, a RFID tag chip and a pair of electrodes. The proposed sensor harvests energy radiated by the RFID reader to power its circuitry. To improve the stability of power supply, a three-stage boost rectifier is customized to rectify the harvested power into dc power and step-up the voltage...
December 11, 2017: Sensors
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
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
V Beck, M Apfelbeck, M Chaloupka, A Kretschmer, F Strittmatter, S Tritschler
BACKGROUND: The development of a stricture of the vesicourethral anastomosis is a serious complication after radical prostatectomy. Strictures occur in 5-8% of patients after radical prostatectomy. SYMPTOMS: Usually the clinical symptoms include an irritative and obstructive component similar to benign prostatic hyperplasia. In rare cases, patients suffer from partial or complete stress incontinence as a result of the anastomotic stricture. DIAGNOSTICS: The diagnostic workup is similar to the procedure for urethral strictures...
January 2018: Der Urologe. Ausg. A
Shane Austin, Mojtaba Tavakoli, Christina Pfeiffer, Julia Seifert, Andrea Mattarei, Diego De Stefani, Mario Zoratti, Karin Nowikovsky
Ca2+ transport across the inner membrane of mitochondria (IMM) is of major importance for their functions in bioenergetics, cell death and signaling. It is therefore tightly regulated. It has been recently proposed that LETM1—an IMM protein with a crucial role in mitochondrial K+ /H+ exchange and volume homeostasis—also acts as a Ca2+ /H+ exchanger. Here we show for the first time that lowering LETM1 gene expression by shRNA hampers mitochondrial K+ /H+ and Na+ /H+ exchange. Decreased exchange activity resulted in matrix K+ accumulation in these mitochondria...
2017: Frontiers in Physiology
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