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mitochondrial complex II

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https://www.readbyqxmd.com/read/28922506/organoruthenium-complexes-with-c-n-ligands-are-highly-potent-cytotoxic-agents-that-act-by-a-new-mechanism-of-action
#1
Vojtech Novohradsky, Jyoti Yellol, Olga Stuchlikova, María Dolores Santana, Hana Kostrhunova, Gorakh Yellol, Jana Kasparkova, Delia Bautista, Jose Ruiz, Viktor Brabec
Our study demonstrates that four novel substitutionally inert C,N-cyclometalated Ru(II) complexes of the type [Ru(C^N)(N^N)2][PF6] containing a handle for functionalization in the C^N ligand are very potent cytotoxic agents against several different human cancer cell lines and are up to 400-fold more potent than clinically used cisplatin. In addition, the investigated ruthenium complexes are less cytotoxic in noncancerous cells, and exhibit higher selectivity for cancer cells than conventional platinum anticancer drugs...
September 18, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28922472/mirna-506-promotes-primary-biliary-cholangitis-like-features-in-cholangiocytes-and-immune-activation
#2
Oihane Erice, Patricia Munoz-Garrido, Javier Vaquero, Maria J Perugorria, Maite G Fernandez-Barrena, Elena Saez, Alvaro Santos-Laso, Ander Arbelaiz, Raul Jimenez-Agüero, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Verónica Torrano, Arkaitz Carracedo, Meenakshisundaram Ananthanarayanan, Marco Marzioni, Jesus Prieto, Ulrich Beuers, Ronald P Oude Elferink, Nicholas F LaRusso, Luis Bujanda, Jose J G Marin, Jesus M Banales
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although PBC etiopathogenesis still remains obscure, development of anti-mitochondrial auto-antibodies against pyruvate dehydrogenase complex-E2 (PDC-E2) is a common feature. MicroRNA (miR) dysregulation occurs in liver and immune cells of PBC patients, but their functional relevance is largely unknown. We previously reported that miR-506 is overexpressed in PBC cholangiocytes and directly targets both Cl(-) /HCO3(-) anion exchanger 2 (AE2) and type III inositol 1,4,5-trisphosphate receptor (InsP3R3), leading to cholestasis...
September 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28919536/neuroprotective-effect-of-5%C3%A9-androst-3%C3%AE-5-6%C3%AE-triol-on-retinal-ganglion-cells-in-a-rat-chronic-ocular-hypertension-model
#3
Yan-Qiu Chen, Shu-Min Zhong, Shu-Ting Liu, Feng Gao, Fang Li, Yuan Zhao, Xing-Huai Sun, Yanying Miao, Zhongfeng Wang
Previous studies have demonstrated that 5ɑ-androst-3β,5,6β-triol (Triol), a synthesized steroid compound, showed notable neuroprotective effect in cultured cortical neurons. In the present study, we explored whether and how Triol have neuroprotective effect on retinal ganglion cells(RGCs) in a chronic ocular hypertension(COH) rat model. COH model was produced by injecting superparamagnetic iron oxide micro-beads into the anterior chamber, and Triol was administrated(4.8μg/100g, i.p., once daily for 4 weeks)...
September 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28913592/chronic-stress-causes-sex-specific-and-structure-specific-alterations-in-mitochondrial-respiratory-chain-activity-in-rat-brain
#4
Carina de Souza Mota, Simone Nardin Weis, Roberto Farina Almeida, Carla Dalmaz, Fátima Therezinha Costa Guma, Letícia Ferreira Pettenuzzo
Chronic restraint stress (CRS) induces a variety of changes in brain function, some of which are mediated by glucocorticoids. The response to stress occurs in a sex-specific way, and may include mitochondrial and synaptic alterations. The synapse is highly dependent on mitochondrial energy supply, and when mitochondria become dysfunctional, they orchestrate cell death. This study aimed to investigate the CRS effects on mitochondrial respiratory chain activity, as well as mitochondrial potential and mass in cell body and synapses using hippocampus, cortex and striatum of male and female rats...
September 14, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28913435/iba57-mutations-abrogate-iron-sulfur-cluster-assembly-leading-to-cavitating-leukoencephalopathy
#5
Akihiko Ishiyama, Chika Sakai, Yuichi Matsushima, Satoru Noguchi, Satomi Mitsuhashi, Yukari Endo, Yukiko K Hayashi, Yoshiaki Saito, Eiji Nakagawa, Hirofumi Komaki, Kenji Sugai, Masayuki Sasaki, Noriko Sato, Ikuya Nonaka, Yu-Ichi Goto, Ichizo Nishino
OBJECTIVE: To determine the molecular factors contributing to progressive cavitating leukoencephalopathy (PCL) to help resolve the underlying genotype-phenotype associations in the mitochondrial iron-sulfur cluster (ISC) assembly system. METHODS: The subjects were 3 patients from 2 families who showed no inconsistencies in either clinical or brain MRI findings as PCL. We used exome sequencing, immunoblotting, and enzyme activity assays to establish a molecular diagnosis and determine the roles of ISC-associated factors in PCL...
October 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28904321/altered-expression-of-mitochondrial-antioxidants-in-oral-squamous-cell-carcinoma
#6
Sumita Banerjee, Saikat Mukherjee, Sanjib Mitra, Pallav Singhal
Reactive oxygen species, if produced in excess by oxidative phosphorylation, contributes to mitochondrial DNA damage and progressive respiratory chain dysfunction, leading to various diseases including carcinogenesis. Mitochondria are susceptible to oxidative stress (OS) owing to lack of introns, protective histones, and DNA repair enzymes. However, mitochondria are protected from OS by numerous antioxidants such as superoxide dismutase 2 (SOD2), catalase, glutaredoxin 2 (GLRX2), reduced glutathione (GSH), glutathione peroxidase (GPX), and thioredoxin 2 (TXN2)...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28891816/syntaphilin-controls-a-mitochondrial-rheostat-for-proliferation-motility-decisions-in-cancer
#7
M Cecilia Caino, Jae Ho Seo, Yuan Wang, Dayana B Rivadeneira, Dmitry I Gabrilovich, Eui Tae Kim, Ashani T Weeraratna, Lucia R Languino, Dario C Altieri
Tumors adapt to an unfavorable microenvironment by controlling the balance between cell proliferation and cell motility, but the regulators of this process are largely unknown. Here, we show that an alternatively spliced isoform of syntaphilin (SNPH), a cytoskeletal regulator of mitochondrial movements in neurons, is directed to mitochondria of tumor cells. Mitochondrial SNPH buffers oxidative stress and maintains complex II-dependent bioenergetics, sustaining local tumor growth while restricting mitochondrial redistribution to the cortical cytoskeleton and tumor cell motility...
September 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28890369/selenium-incorporated-guar-gum-nanoparticles-safeguards-mitochondrial-bioenergetics-during-ischemia-reperfusion-injury-in-h9c2-cardiac-cells
#8
R S Soumya, Prathapan Ayyappan, P Salin Raj, V P Vineetha, K G Raghu
The application of nanotechnology has created high impact in diagnosis and prognosis of various disorders including cardiovascular diseases. In the present study, we investigated the beneficial effect of selenium incorporated guar gum nanoparticles (SGG) compared to nascent selenium (Se) and guar gum nanoparticle (GGN) against ischemia-reperfusion induced alterations in oxidative phosphorylation and energy metabolism in H9c2 cardiac cells. Ischemia and reperfusion were induced for 1h. The alterations in activities of various complexes (complex 1, II, III and IV) of mitochondrial electron transport chain (ETC), aconitase activity, oxygen consumption rate, and the ATP content were seen...
September 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28888620/the-caspase-8-bid-cytochrome-c-axis-links-signals-from-death-receptors-to-mitochondrial-reactive-oxygen-species-production
#9
Wan-Sung Kim, Kwang-Soon Lee, Ji-Hee Kim, Chun-Ki Kim, Gwangsoo Lee, Jongseon Choe, Moo-Ho Won, Tae-Hyoung Kim, Dooil Jeoung, Hansoo Lee, Ji-Yoon Kim, Mi Ae Jeong, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
Ligation of the death receptors for TNF-α, FasL, and TRAIL triggers two common pathways, caspase-dependent intrinsic apoptosis and intracellular reactive oxygen species (ROS) generation. The apoptotic pathway is well characterized; however, a signaling linker between the death receptor and ROS production has not been clearly elucidated. Here, we found that death receptor-induced ROS generation was strongly inhibited by mitochondrial complex I and II inhibitors, but not by inhibitors of NADPH oxidase, lipoxygenase, cyclooxygenase or xanthine oxidase, indicating that ROS are mostly generated by the impairment of the mitochondrial respiratory chain...
September 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28887692/molecular-and-biochemical-evidence-on-the-protective-role-of-ellagic-acid-and-silybin-against-oxidative-stress-induced-cellular-aging
#10
Maryam Baeeri, Solmaz Mohammadi-Nejad, Mahban Rahimifard, Mona Navaei-Nigjeh, Shermineh Moeini-Nodeh, Reza Khorasani, Mohammad Abdollahi
Aging is a natural process in living organisms that is defined by some molecular and cellular changes with time. Various causes such as mitochondrial DNA aberrations, aggregation of proteins, telomere shortening, and oxidative stress have an influential role in aging of the cells. Natural antioxidants are compounds that are potent to protect the body from detrimental effects of molecules such as free radicals. The aim of this study was to evaluate the anti-aging properties of ellagic acid (EA) and silybin (SIL), as natural antioxidant compounds on rat embryonic fibroblast (REF) cells...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28884428/in-vitro-and-in-vivo-anti-proliferative-evaluation-of-bis-4-4-tolyl-2-2-6-2%C3%A2-terpyridine-copper-ii-complex-against-ehrlich-ascites-carcinoma-tumors
#11
Dharmasivam Mahendiran, Raju Senthil Kumar, Vijayan Viswanathan, Devadasan Velmurugan, Aziz Kalilur Rahiman
The bis(4'-(4-tolyl)-2,2':6',2″-terpyridine)copper(II) complex [Cu(ttpy)2]Cl2 was synthesized and authenticated by single crystal analysis, which shows distorted octahedral geometry around copper(II) ion. The crystal packing is stabilized by C-H···π inter and intramolecular interactions. The complex was found to be lipophilic as determined by shake-flask method. In vitro cytotoxicity of the complex was tested against Ehrlich ascites carcinoma (EAC) and L6 myotube cell lines. The complex exhibit potent cytotoxicity with respect to the commercially available anticancer drug cisplatin...
September 7, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28883788/loss-of-mitochondrial-ndufs4-in-striatal-medium-spiny-neurons-mediates-progressive-motor-impairment-in-a-mouse-model-of-leigh-syndrome
#12
Byron Chen, Jessica Hui, Kelsey S Montgomery, Alejandro Gella, Irene Bolea, Elisenda Sanz, Richard D Palmiter, Albert Quintana
Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS) is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28874733/mitochondrial-permeability-transition-pore-sensitivity-to-opening-and-mechanistic-dependence-on-substrate-availability
#13
Thomas Briston, Malcolm Roberts, Sian Lewis, Ben Powney, James M Staddon, Gyorgy Szabadkai, Michael R Duchen
Mitochondrial Ca(2+) uptake has a key role in cellular Ca(2+) homeostasis. Excessive matrix Ca(2+) concentrations, especially when coincident with oxidative stress, precipitate opening of an inner mitochondrial membrane, high-conductance channel: the mitochondrial permeability transition pore (mPTP). mPTP opening has been implicated as a final cell death pathway in numerous diseases and therefore understanding conditions dictating mPTP opening is crucial for developing targeted therapies. Here, we have investigated the impact of mitochondrial metabolic state on the probability and consequences of mPTP opening...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28873407/photo-affinity-labelling-and-biochemical-analyses-identify-the-target-of-trypanocidal-simplified-natural-product-analogues
#14
Lindsay B Tulloch, Stefanie K Menzies, Andrew L Fraser, Eoin R Gould, Elizabeth F King, Marija K Zacharova, Gordon J Florence, Terry K Smith
Current drugs to treat African sleeping sickness are inadequate and new therapies are urgently required. As part of a medicinal chemistry programme based upon the simplification of acetogenin-type ether scaffolds, we previously reported the promising trypanocidal activity of compound 1, a bis-tetrahydropyran 1,4-triazole (B-THP-T) inhibitor. This study aims to identify the protein target(s) of this class of compound in Trypanosoma brucei to understand its mode of action and aid further structural optimisation...
September 5, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28870729/tigecylcine-induced-inhibition-of-mitochondrial-mtdna-translation-may-cause-a-lethal-mitochondrial-dysfunction-in-human
#15
S J Vandecasteele, S Seneca, J Smet, M Reynders, J De Ceulaer, A V Vanlander, R Van Coster
OBJECTIVES: A 65-year old patient developed an unexplained and ultimately lethal metabolic acidosis under prolonged treatment with tigecycline. Tigecycline is known to have a selective inhibitory effect on eukaryotic mitochondrial translation. The underlying molecular mechanisms of the metabolic acidosis in this patient were explored. METHODS: OXPHOS analysis, blue native PAGE followed by in-gel activity staining in mitochondria, molecular analysis of mtDNA for genomic rearrangements and sequencing of the rRNA genes was performed on the proband's skeletal muscle...
September 1, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28868496/pancreatic-mitochondrial-complex-i-exhibits-aberrant-hyperactivity-in-diabetes
#16
Jinzi Wu, Xiaoting Luo, Nopporn Thangthaeng, Nathalie Sumien, Zhenglan Chen, Margaret A Rutledge, Siqun Jing, Michael J Forster, Liang-Jun Yan
It is well established that NADH/NAD(+) redox balance is heavily perturbed in diabetes, and the NADH/NAD(+) redox imbalance is a major source of oxidative stress in diabetic tissues. In mitochondria, complex I is the only site for NADH oxidation and NAD(+) regeneration and is also a major site for production of mitochondrial reactive oxygen species (ROS). Yet how complex I responds to the NADH/NAD(+) redox imbalance and any potential consequences of such response in diabetic pancreas have not been investigated...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28866380/mitochondrial-transition-ros-spike-mtrs-results-from-coordinated-activities-of-complex-i-and-nicotinamide-nucleotide-transhydrogenase
#17
Mahmoud S Sharaf, Don Stevens, Collins Kamunde
Mitochondria exhibit suppressed ATP production, membrane potential (∆Ψmt) polarization and reactive oxygen species (ROS) bursts during some cellular metabolic transitions. Although mitochondrial ROS release is influenced by ∆Ψmt and respiratory state, the relationship between these properties remains controversial primarily because they have not been measured simultaneously. We developed a multiparametric method for probing mitochondrial function that allowed precise characterization of the temporal relationship between ROS, ∆Ψmt and respiration...
August 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28864949/skeletal-muscle-mitochondrial-mass-is-linked-to-lipid-and-metabolic-profile-in-individuals-with-spinal-cord-injury
#18
Laura C O'Brien, Qun Chen, Jeannie Savas, Edward J Lesnefsky, Ashraf S Gorgey
PURPOSE: Changes in metabolism and body composition after spinal cord injury (SCI) predispose individuals to obesity, type II diabetes, and cardiovascular disease. A link between lean mass and skeletal muscle mitochondrial mass has been reported but it is unknown how skeletal muscle mitochondrial mass and activity impact metabolic health. This study examined the relationship between skeletal muscle mitochondrial mass, activity and metabolic profile in individuals with chronic SCI. METHODS: Twenty-two men with motor complete SCI participated in the study...
September 1, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28857403/in-vivo-chlorophyll-fluorescence-screening-allows-the-isolation-of-a-chlamydomonas-mutant-defective-for-ndufaf3-an-assembly-factor-involved-in-mitochondrial-complex-i-assembly
#19
S Massoz, M Hanikenne, B Bailleul, N Coosemans, M Radoux, H Miranda-Astudillo, P Cardol, V Larosa, C Remacle
The qualitative screening method to select complex I mutants in the microalga Chlamydomonas, based on reduced growth under heterotrophic condition, is not suited for high throughput screening. In order to develop a fast screening method based on measurements of chlorophyll fluorescence, we first demonstrated that complex I mutants displayed decreased photosystem II efficiency in the genetic background of a photosynthetic mutation leading to reduced formation of the electrochemical proton gradient in the chloroplast (pgrl1 mutation)...
August 30, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28852135/peptide-ss-31-upregulates-frataxin-expression-and-improves-the-quality-of-mitochondria-implications-in-the-treatment-of-friedreich-ataxia
#20
Hongting Zhao, Huihui Li, Shuangying Hao, Jiping Chen, Jing Wu, Chuanhui Song, Meng Zhang, Tong Qiao, Kuanyu Li
Friedreich ataxia is a progressive neurodegenerative disease caused by the expansion of GAA trinucleotide repeats within the first intron of the FXN gene, which encodes frataxin. The pathophysiology of the disease is thought to be derived from the decrease of Fe-S cluster biogenesis due to frataxin deficiency. There is currently no effective treatment for the disease. In our study, we demonstrated that treatment with the mitochondrion-targeted peptide SS-31 reduced frataxin deficiency-induced oxidative stress in lymphoblasts and fibroblasts derived from patients...
August 29, 2017: Scientific Reports
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