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https://www.readbyqxmd.com/read/29725115/micu3-is-a-tissue-specific-enhancer-of-mitochondrial-calcium-uptake
#1
Maria Patron, Veronica Granatiero, Javier Espino, Rosario Rizzuto, Diego De Stefani
The versatility and universality of Ca2+ as intracellular messenger is guaranteed by the compartmentalization of changes in [Ca2+ ]. In this context, mitochondrial Ca2+ plays a central role, by regulating both specific organelle functions and global cellular events. This versatility is also guaranteed by a cell type-specific Ca2+ signaling toolkit controlling specific cellular functions. Accordingly, mitochondrial Ca2+ uptake is mediated by a multimolecular structure, the MCU complex, which differs among various tissues...
May 3, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29713599/-caralluma-umbellata-haw-protects-liver-against-paracetamol-toxicity-and-inhibits-cyp2e1
#2
Pavan Kumar Bellamakondi, Ashok Godavarthi, Mohammed Ibrahim
Introduction: Paracetamol is a potent hepatotoxin and may cause severe acute hepatocellular injury. The present study was intended to assess the hepatoprotective potential of Caralluma umbellata Haw. (Asclepiadaceae) ( C. umbellata ) against paracetamol-induced hepatotoxicity in vitro and in vivo experimental models. Methods: Preliminary analysis for antioxidant and hepatoprotective property was evaluated for methanolic (MCU), aqueous (ACU) and hydro methanolic (HCU) extracts of C. umbellata using in vitro cell-free antioxidant such as DPPH, ABTS, nitric oxide, lipid peroxidation models and cell-based hepatoprotective study using BRL3A cells...
2018: BioImpacts: BI
https://www.readbyqxmd.com/read/29709004/mcu-knockdown-attenuates-high-glucose-induced-inflammation-through-regulating-mapks-nf-%C3%AE%C2%BAb-pathways-and-ros-production-in-hepg2-cells
#3
Ghodratollah Panahi, Parvin Pasalar, Mina Zare, Rosario Rizzuto, Reza Meshkani
Mitochondrial Ca2+ is a key regulator of organelle physiology and the excessive increase in mitochondrial calcium is associated with the oxidative stress. In the present study, we investigated the molecular mechanisms linking mitochondrial calcium to inflammatory and coagulative responses in hepatocytes exposed to high glucose (HG) (33mM glucose). Treatment of HepG2 cells with HG for 24 h induced insulin resistance, as demonstrated by an impairment of insulin-stimulated Akt phosphorylation. HepG2 treatment with HG led to an increase in mitochondrial Ca2+ uptake, while cytosolic calcium remained unchanged...
2018: PloS One
https://www.readbyqxmd.com/read/29694881/miro-1-determines-mitochondrial-shape-transition-upon-gpcr-activation-and-ca-2-stress
#4
Neeharika Nemani, Edmund Carvalho, Dhanendra Tomar, Zhiwei Dong, Andrea Ketschek, Sarah L Breves, Fabián Jaña, Alison M Worth, Julie Heffler, Palaniappan Palaniappan, Aparna Tripathi, Ramasamy Subbiah, Massimo F Riitano, Ajay Seelam, Thomas Manfred, Kie Itoh, Shuxia Meng, Hiromi Sesaki, William J Craigen, Sudarsan Rajan, Santhanam Shanmughapriya, Jeffrey Caplan, Benjamin L Prosser, Donald L Gill, Peter B Stathopulos, Gianluca Gallo, David C Chan, Prashant Mishra, Muniswamy Madesh
Mitochondria shape cytosolic calcium ([Ca2+ ]c ) transients and utilize the mitochondrial Ca2+ ([Ca2+ ]m ) in exchange for bioenergetics output. Conversely, dysregulated [Ca2+ ]c causes [Ca2+ ]m overload and induces permeability transition pore and cell death. Ablation of MCU-mediated Ca2+ uptake exhibited elevated [Ca2+ ]c and failed to prevent stress-induced cell death. The mechanisms for these effects remain elusive. Here, we report that mitochondria undergo a cytosolic Ca2+ -induced shape change that is distinct from mitochondrial fission and swelling...
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29686046/mcu-interacts-with-miro1-to-modulate-mitochondrial-functions-in-neurons
#5
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
#6
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/29599132/camkii-ca-2-calmodulin-dependent-kinase-ii-in-mitochondria-of-smooth-muscle-cells-controls-mitochondrial-mobility-migration-and-neointima-formation
#7
Emily K Nguyen, Olha M Koval, Paige Noble, Kim Broadhurst, Chantal Allamargot, Meng Wu, Stefan Strack, William H Thiel, Isabella M Grumbach
OBJECTIVE: The main objective of this study is to define the mechanisms by which mitochondria control vascular smooth muscle cell (VSMC) migration and impact neointimal hyperplasia. APPROACH AND RESULTS: The multifunctional CaMKII (Ca2+ /calmodulin-dependent kinase II) in the mitochondrial matrix of VSMC drove a feed-forward circuit with the mitochondrial Ca2+ uniporter (MCU) to promote matrix Ca2+ influx. MCU was necessary for the activation of mitochondrial CaMKII (mtCaMKII), whereas mtCaMKII phosphorylated MCU at the regulatory site S92 that promotes Ca2+ entry...
March 29, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29549313/astrocytic-metabolic-switch-is-a-novel-etiology-for-cocaine-and-hiv-1-tat-mediated-neurotoxicity
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/29531160/ripk1-binds-mcu-to-mediate-induction-of-mitochondrial-ca2-uptake-and-promote-colorectal-oncogenesis
#11
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
https://www.readbyqxmd.com/read/29513617/dynamic-transitions-between-marijuana-use-and-cigarette-smoking-among-us-adolescents-and-emerging-adults
#12
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...
2018: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/29492538/an-embedded-device-for-real-time-noninvasive-intracranial-pressure-estimation
#13
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
https://www.readbyqxmd.com/read/29491367/redox-crosstalk-at-endoplasmic-reticulum-er-membrane-contact-sites-mcs-uses-toxic-waste-to-deliver-messages
#14
REVIEW
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
https://www.readbyqxmd.com/read/29484354/temporal-associations-between-caregiving-approach-behavioral-symptoms-and-observable-indicators-of-aspiration-in-nursing-home-residents-with-dementia
#15
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
https://www.readbyqxmd.com/read/29451229/m-aaa-proteases-mitochondrial-calcium-homeostasis-and-neurodegeneration
#16
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/29363836/role-of-mitochondrial-ca-2-uniporter-in-remifentanil-induced-postoperative-allodynia
#17
Aizhu Lu, Hongyi Lei, Le Li, Luying Lai, Wenbin Liang, Shiyuan Xu
Opioid-induced hyperalgesia (OIH) and allodynia 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. This 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...
February 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29354781/suppression-of-arrhythmia-by-enhancing-mitochondrial-ca-2-uptake-in-catecholaminergic-ventricular-tachycardia-models
#18
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
https://www.readbyqxmd.com/read/29323106/sequential-forward-and-reverse-transport-of-the-na-ca-2-exchanger-generates-ca-2-oscillations-within-mitochondria
#19
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/29286188/the-mitochondrial-calcium-uniporter-complex-in-trypanosomes
#20
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
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