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Mitochondria complex

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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
#1
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/28649426/conserved-and-species-specific-molecular-denominators-in-mammalian-skeletal-muscle-aging
#2
Evi M Mercken, Miriam Capri, Bethany A Carboneau, Maria Conte, Juliana Heidler, Aurelia Santoro, Alejandro Martin-Montalvo, Marta Gonzalez-Freire, Husam Khraiwesh, José A González-Reyes, Ruin Moaddel, Yongqing Zhang, Kevin G Becker, José M Villalba, Julie A Mattison, Ilka Wittig, Claudio Franceschi, Rafael de Cabo
Aging is a complex phenomenon involving functional decline in multiple physiological systems. We undertook a comparative analysis of skeletal muscle from four different species, i.e. mice, rats, rhesus monkeys, and humans, at three different representative stages during their lifespan (young, middle, and old) to identify pathways that modulate function and healthspan. Gene expression profiling and computational analysis revealed that pathway complexity increases from mice to humans, and as mammals age, there is predominantly an upregulation of pathways in all species...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28649367/nitric-oxide-signalling-and-neuronal-nitric-oxide-synthase-in-the-heart-under-stress
#3
REVIEW
Yin Hua Zhang
Nitric oxide (NO) is an imperative regulator of the cardiovascular system and is a critical mechanism in preventing the pathogenesis and progression of the diseased heart. The scenario of bioavailable NO in the myocardium is complex: 1) NO is derived from both endogenous NO synthases (endothelial, neuronal, and/or inducible NOSs [eNOS, nNOS, and/or iNOS]) and exogenous sources (entero-salivary NO pathway) and the amount of NO from exogenous sources varies significantly; 2) NOSs are located at discrete compartments of cardiac myocytes and are regulated by distinctive mechanisms under stress; 3) NO regulates diverse target proteins through different modes of post-transcriptional modification (soluble guanylate cyclase [sGC]/cyclic guanosine monophosphate [cGMP]/protein kinase G [PKG]-dependent phosphorylation, S-nitrosylation, and transnitrosylation); 4) the downstream effectors of NO are multidimensional and vary from ion channels in the plasma membrane to signalling proteins and enzymes in the mitochondria, cytosol, nucleus, and myofilament; 5) NOS produces several radicals in addition to NO (e...
2017: F1000Research
https://www.readbyqxmd.com/read/28646906/modulation-of-oxidative-phosphorylation-and-redox-homeostasis-in-mitochondrial-ndufs4-deficiency-via-mesenchymal-stem-cells
#4
Marlen Melcher, Katharina Danhauser, Annette Seibt, Özer Degistirici, Fabian Baertling, Arun Kumar Kondadi, Andreas S Reichert, Werner J H Koopman, Peter H G M Willems, Richard J Rodenburg, Ertan Mayatepek, Roland Meisel, Felix Distelmaier
BACKGROUND: Disorders of the oxidative phosphorylation (OXPHOS) system represent a large group among the inborn errors of metabolism. The most frequently observed biochemical defect is isolated deficiency of mitochondrial complex I (CI). No effective treatment strategies for CI deficiency are so far available. The purpose of this study was to investigate whether and how mesenchymal stem cells (MSCs) are able to modulate metabolic function in fibroblast cell models of CI deficiency. METHODS: We used human and murine fibroblasts with a defect in the nuclear DNA encoded NDUFS4 subunit of CI...
June 24, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28646657/-half-sandwich-schiff-base-ir-iii-complexes-as-anticancer-agents
#5
Ze-Dong Mou, Ning Deng, Feng Zhang, Jiaying Zhang, Juan Cen, Xia Zhang
A series of "half-sandwich" Schiff-base Ir(III) complexes were synthesized and investigated for their in vitro activities against the leukemia K562 cell line. These compounds demonstrated antiproliferative activities against K562 cells with IC50 values of 0.26-4.77 μM. In particular, compound 10c showed cytotoxicity against five cancer cell lines/sublines and stronger activities than cisplatin in K562, K562/A02, MCF-7, MCF-7/ADM, and A549 cells. Mechanism studies illustrated that compound 10c increased the level of reactive oxygen species and induced apoptosis of K562 cells...
June 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28645153/defective-mitochondrial-rna-processing-due-to-pnpt1-variants-causes-leigh-syndrome
#6
Sanna Matilainen, Christopher J Carroll, Uwe Richter, Liliya Euro, Max Pohjanpelto, Anders Paetau, Pirjo Isohanni, Anu Suomalainen
Leigh syndrome is a severe infantile encephalopathy with an exceptionally variable genetic background. We studied the exome of a child manifesting with Leigh syndrome at one month of age and progressing to death by the age of 2.4 years, and identified novel compound heterozygous variants in PNPT1, encoding the polynucleotide phosphorylase (PNPase). Expression of the wild type PNPT1 in the subject's myoblasts functionally complemented the defects, and the pathogenicity was further supported by structural predictions and protein and RNA analyses...
June 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28644434/ageing-and-hypoxia-cause-protein-aggregation-in-mitochondria
#7
Daniel M Kaufman, Xia Wu, Barbara A Scott, Omar A Itani, Marc R Van Gilst, James E Bruce, C Michael Crowder
Aggregation of cytosolic proteins is a pathological finding in disease states, including ageing and neurodegenerative diseases. We have previously reported that hypoxia induces protein misfolding in Caenorhabditis elegans mitochondria, and electron micrographs suggested protein aggregates. Here, we seek to determine whether mitochondrial proteins actually aggregate after hypoxia and other cellular stresses. To enrich for mitochondrial proteins that might aggregate, we performed a proteomics analysis on purified C...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28642134/mitochondrial-potassium-channels-in-cell-death
#8
Vanessa Checchetto, Michele Azzolini, Roberta Peruzzo, Paola Capitanio, Luigi Leanza
Mitochondria are intracellular organelles involved in several processes from bioenergetics to cell death. In the latest years, ion channels are arising as new possible targets in controlling several cellular functions. The discovery that several plasma membrane located ion channels have intracellular counterparts, has now implemented this consideration and the number of studies enforcing the understanding of their role in different metabolic pathways. In this review, we will discuss the recent updates in the field, focusing our attention on the involvement of potassium channels during mitochondrial mediated apoptotic cell death...
June 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28642043/mitochondrial-cx43-an-important-component-of-cardiac-preconditioning
#9
REVIEW
Antonio Rodríguez-Sinovas, Marisol Ruiz-Meana, Amanda Denuc, David García-Dorado
Connexin 43 (Cx43) forms gap junction channels that are essential for the propagation of electrical depolarization in cardiomyocytes, but also with important roles in the pathophysiology of reperfusion injury. However, more recent studies have shown that Cx43 has also important functions independent from intercellular communication between adjacent cardiomyocytes. Some of these actions have been related to the presence of Cx43 in the mitochondria of these cells (mitoCx43). The functions of mitoCx43 have not been completely elucidated, but there is strong evidence indicating that mitoCx43 modulates mitochondrial respiration at respiratory complex I, production of radical oxygen species and ATP synthesis...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28642010/magnetic-nanogels-as-dual-triggered-anticancer-drug-delivery-toxicity-evaluation-on-isolated-rat-liver-mitochondria
#10
Somayeh Sadighian, Kobra Rostamizadeh, Mehrdad Hamidi, Mir-Jamal Hosseini, Hassan Hosseini-Monfared
This study aimed to evaluate bio-safety of magnetic chitosan nanogels as dual triggered drug carrier for doxorubicin through analysis of mitochondrial function. In the present study, chitosan/TPP nanogels containing magnetite nanoparticles (NPs) were prepared according to the ionotropic gelation method as novel pH-sensitive magnetic nanogels. The NPs showed outstanding entrapment efficiency for doxorubicin (76.6%) with a sustained and high extent of drug release in the acidic media (pH=5-7) compared to the neutral media...
June 19, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28640814/a-novel-algorithm-identifies-stress-induced-alterations-in-mitochondrial-connectivity-and-inner-membrane-structure-from-confocal-images
#11
Mathieu Ouellet, Gérald Guillebaud, Valerie Gervais, David Lupien St-Pierre, Marc Germain
Mitochondria exist as a highly interconnected network that is exquisitely sensitive to variations in nutrient availability, as well as a large array of cellular stresses. Changes in length and connectivity of this network, as well as alterations in the mitochondrial inner membrane (cristae), regulate cell fate by controlling metabolism, proliferation, differentiation, and cell death. Given the key roles of mitochondrial dynamics, the process by which mitochondria constantly fuse and fragment, the measure of mitochondrial length and connectivity provides crucial information on the health and activity of various cell populations...
June 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28640448/overview-of-the-muscle-cytoskeleton
#12
Christine A Henderson, Christopher G Gomez, Stefanie M Novak, Lei Mi-Mi, Carol C Gregorio
Cardiac and skeletal striated muscles are intricately designed machines responsible for muscle contraction. Coordination of the basic contractile unit, the sarcomere, and the complex cytoskeletal networks are critical for contractile activity. The sarcomere is comprised of precisely organized individual filament systems that include thin (actin), thick (myosin), titin, and nebulin. Connecting the sarcomere to other organelles (e.g., mitochondria and nucleus) and serving as the scaffold to maintain cellular integrity are the intermediate filaments...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28640253/a-role-for-tspo-in-mitochondrial-ca-2-homeostasis-and-redox-stress-signaling
#13
Jemma Gatliff, Daniel A East, Aarti Singh, Maria Soledad Alvarez, Michele Frison, Ivana Matic, Caterina Ferraina, Natalie Sampson, Federico Turkheimer, Michelangelo Campanella
The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca(2+) signaling leading to a parallel increase in the cytosolic Ca(2+) pools that activate the Ca(2+)-dependent NADPH oxidase (NOX) thereby increasing ROS...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28639457/glyoxal-toxicity-in-isolated-rat-liver-mitochondria
#14
M Goudarzi, H Kalantari, M Rezaei
Glyoxal is a physiological metabolite formed by lipid peroxidation, ascorbate autoxidation, oxidative degradation of glucose, and degradation of glycated proteins. Glyoxal has been linked to oxidative stress and can cause a number of cellular damages, including covalent modification of amino and thiol groups of proteins to form advanced glycation end products. However, the mechanism of glyoxal toxicity has not been fully understood. In this study, we have focused on glyoxal toxicity in isolated rat liver mitochondria...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28639360/the-mechanism-of-coupling-between-oxido-reduction-and-proton-translocation-in-respiratory-chain-enzymes
#15
Sergio Papa, Giuseppe Capitanio, Francesco Papa
The respiratory chain of mitochondria and bacteria is made up of a set of membrane-associated enzyme complexes which catalyse sequential, stepwise transfer of reducing equivalents from substrates to oxygen and convert redox energy into a transmembrane protonmotive force (PMF) by proton translocation from a negative (N) to a positive (P) aqueous phase separated by the coupling membrane. There are three basic mechanisms by which a membrane-associated redox enzyme can generate a PMF. These are membrane anisotropic arrangement of the primary redox catalysis with: (i) vectorial electron transfer by redox metal centres from the P to the N side of the membrane; (ii) hydrogen transfer by movement of quinones across the membrane, from a reduction site at the N side to an oxidation site at the P side; (iii) a different type of mechanism based on co-operative allosteric linkage between electron transfer at the metal redox centres and transmembrane electrogenic proton translocation by apoproteins...
June 21, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28638907/ruthenium-ii-p-cymene-complexes-of-a-benzimidazole-based-ligand-capable-of-vegfr2-inhibition-hydrolysis-reactivity-and-cytotoxicity-studies
#16
Sudipta Bhattacharyya, Kallol Purkait, Arindam Mukherjee
The design of Ru or other metal-based anticancer agents may achieve better and faster optimization if the ligands used are also designed to have standalone functions. In this scenario, even after dissociation from the metal complex under adverse conditions, the ligand would have anti-cancer properties. In our work, we have generated a bispyrazole-containing benzimidazole ligand with potency against vascular endothelial growth factor receptor 2 (VEGFR2), which is known to have roles in vasculogenesis/angiogenesis...
June 22, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28638095/mitochondria-localization-induced-self-assembly-of-peptide-amphiphiles-for-cellular-dysfunction
#17
M T Jeena, L Palanikumar, Eun Min Go, Inhye Kim, Myoung Gyun Kang, Seonik Lee, Sooham Park, Huyeon Choi, Chaekyu Kim, Seon-Mi Jin, Sung Chul Bae, Hyun Woo Rhee, Eunji Lee, Sang Kyu Kwak, Ja-Hyoung Ryu
Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful strategy for controlling cellular fate. A phenylalanine dipeptide (FF) with a mitochondria-targeting moiety, triphenyl phosphonium (Mito-FF), preferentially accumulates inside mitochondria and reaches the critical aggregation concentration to form a fibrous nanostructure, which is monitored by confocal laser scanning microscopy and transmission electron microscopy...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28637866/endoplasmic-reticulum-mitochondria-junction-is-required-for-iron-homeostasis
#18
Yong Xue, Stefan Schmollinger, Narsis Attar, Oscar Campos, Maria Vogelauer, Michael F Carey, Sabeeha S Merchant, Siavash K Kurdistani
The Endoplasmic Reticulum-Mitochondria Encounter Structure (ERMES) is a protein complex that physically tethers the two organelles to each other and creates the physical basis for communication between them. ERMES functions in lipid and calcium exchange between the ER and mitochondria, protein import into mitochondria and maintenance of mitochondrial morphology and genome. Here we report that ERMES is also required for iron homeostasis. Loss of ERMES components activates an Aft1-dependent iron deficiency response even in iron-replete conditions, leading to accumulation of excess iron inside the cell...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28637353/hallmarks-of-pulmonary-hypertension-mesenchymal-and-inflammatory-cell-metabolic-reprogramming
#19
Angelo D'Alessandro, Karim El Kasmi, Lydie Plecita-Hlavata, Petr Jezek, Min Li, Hui Zhang, Sachin A Gupte, Kurt Randall Stenmark
The molecular events that promote the development of pulmonary hypertension (PH) are complex and incompletely understood. The complex interplay between the pulmonary vasculature and its immediate microenvironment involving cells of immune system (i.e. macrophages) promotes a persistent inflammatory state, pathological angiogenesis and fibrosis that is driven by metabolic reprogramming of mesenchymal and immune cells. Consistent with previous findings in the field of cancer metabolism, increased glycolytic rates, incomplete glucose and glutamine oxidation to support anabolism and anaplerosis, altered lipid synthesis/oxidation ratios, increased one-carbon metabolism and activation of the pentose phosphate pathway to support nucleoside synthesis are but some of the key metabolic signatures of vascular cells in PH...
June 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28634818/sg2na-is-a-regulator-of-endoplasmic-reticulum-er-homeostasis-as-its-depletion-leads-to-er-stress
#20
Buddhi Prakash Jain, Shweta Pandey, Nikhat Saleem, Goutam K Tanti, Shalini Mishra, Shyamal K Goswami
SG2NA belongs to a three-member striatin subfamily of WD40 repeat superfamily of proteins. It has multiple protein-protein interaction domains involved in assembling supramolecular signaling complexes. Earlier, we had demonstrated that there are at least five variants of SG2NA generated by alternative splicing, intron retention, and RNA editing. Such versatile and dynamic mode of regulation implicates it in tissue development. In order to shed light on its role in cell physiology, total proteome analysis was performed in NIH3T3 cells depleted of 78 kDa SG2NA, the only isoform expressing therein...
June 21, 2017: Cell Stress & Chaperones
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