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https://www.readbyqxmd.com/read/28934388/loss-of-slc25a46-causes-neurodegeneration-by-affecting-mitochondrial-dynamics-and-energy-production-in-mice
#1
Zhuo Li, Yanyan Peng, Robert B Hufnagel, Yueh-Chiang Hu, Chuntao Zhao, Luis F Queme, Zaza Khuchua, Ashley M Driver, Fei Dong, Q Richard Lu, Diana M Lindquist, Michael P Jankowski, Rolf W Stottmann, Winston W Y Kao, Taosheng Huang
Recently, we identified biallelic mutations of SLC25A46 in patients with multiple neuropathies. Functional studies revealed that SLC25A46 may play an important role in mitochondrial dynamics by mediating mitochondrial fission. However, the cellular basis and pathogenic mechanism of the SLC25A46-related neuropathies are not fully understood. Thus, we generated a Slc25a46 knock-out mouse model. Mice lacking SLC25A46 displayed severe ataxia, mainly caused by degeneration of Purkinje cells. Increased numbers of small, unmyelinated and degenerated optic nerves as well as loss of retinal ganglion cells indicated optic atrophy...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28931652/responsive-monitoring-of-mitochondrial-redox-states-in-heart-muscle-predicts-impending-cardiac-arrest
#2
Dorothy A Perry, Joshua W Salvin, Padraic Romfh, Peili Chen, Kalyani Krishnamurthy, Lindsay M Thomson, Brian D Polizzotti, Francis X McGowan, Daryoosh Vakhshoori, John N Kheir
Assessing the adequacy of oxygen delivery to tissues is vital, particularly in the fields of intensive care medicine and surgery. As oxygen delivery to a cell becomes deficient, changes in mitochondrial redox state precede changes in cellular function. We describe a technique for the continuous monitoring of the mitochondrial redox state on the epicardial surface using resonance Raman spectroscopy. We quantify the reduced fraction of specific electron transport chain cytochromes, a metric we name the resonance Raman reduced mitochondrial ratio (3RMR)...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28928443/affected-energy-metabolism-under-manganese-stress-governs-cellular-toxicity
#3
Gursharan Kaur, Vineet Kumar, Amit Arora, Ajay Tomar, Ashish, Runa Sur, Dipak Dutta
Excessive manganese exposure is toxic, but a comprehensive biochemical picture of this assault is poorly understood. Whether oxidative stress or reduced energy metabolism under manganese exposure causes toxicity is still a debate. To address this, we chose Δmnt P Escherichia coli, a highly manganese-sensitive strain, in this study. Combining microarray, proteomics, and biochemical analyses, we show that the chronic manganese exposure rewires diverse regulatory and metabolic pathways. Manganese stress affects protein and other macromolecular stability, and envelope biogenesis...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928420/andreev-molecules-in-semiconductor-nanowire-double-quantum-dots
#4
Zhaoen Su, Alexandre B Tacla, Moïra Hocevar, Diana Car, Sébastien R Plissard, Erik P A M Bakkers, Andrew J Daley, David Pekker, Sergey M Frolov
Chains of quantum dots coupled to superconductors are promising for the realization of the Kitaev model of a topological superconductor. While individual superconducting quantum dots have been explored, control of longer chains requires understanding of interdot coupling. Here, double quantum dots are defined by gate voltages in indium antimonide nanowires. High transparency superconducting niobium titanium nitride contacts are made to each of the dots in order to induce superconductivity, as well as probe electron transport...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28925677/polypeptide-composite-particle-assisted-organization-of-%C3%AF-conjugated-polymers-into-highly-crystalline-coffee-stains
#5
Cornelia Rosu, Ping-Hsun Chu, Christopher J Tassone, Katherine Park, Paul L Balding, Jung Ok Park, Mohan Srinivasarao, Elsa Reichmanis
We demonstrate that homopolypeptides covalently tethered to anisotropically shaped silica particles induce crystalline ordering of representative semiconducting polymers. Films drop-cast from chloroform dispersions of poly(γ-stearyl-l-glutamate) (PSLG) composite particles and poly(3-hexythiophene) (P3HT) led to highly ordered crystalline structures of P3HT. Hydrophobic-hydrophobic interactions between the alkyl side chains of P3HT and PSLG were the main driving force for P3HT chain ordering into the crystalline assemblies...
September 19, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28925551/clade-ii-nitrous-oxide-respiration-of-wolinella-succinogenes-depends-on-the-nosg-c1-c2-h-electron-transport-module-nosb-and-a-rieske-cytochrome-bc-complex
#6
Sascha Hein, Samantha Witt, Jörg Simon
Microbial reduction of nitrous oxide (N2 O) is an environmentally significant process in the biogeochemical nitrogen cycle. However, it has been recognized only recently that the gene encoding N2 O reductase (nosZ) is organized in varying genetic contexts, thereby defining clade I (or "typical") and clade II (or "atypical") N2 O reductases and nos gene clusters. This study addresses the enzymology of the clade II Nos system from Wolinella succinogenes, a nitrate-ammonifying and N2 O-respiring Epsilonproteobacterium that contains a cytochrome c N2 O reductase (cNosZ)...
September 19, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28924017/in-silico-analysis-of-the-regulation-of-the-photosynthetic-electron-transport-chain-in-c3-plants
#7
Alejandro Morales, Xinyou Yin, Jeremy Harbinson, Steven Michiel Driever, Jaap Molenaar, David M Kramer, Paul Struik
We present a new simulation model of the reactions in the photosynthetic electron transport chain of C3 species. We show that including recent insights about the regulation of the thylakoid proton motive force, ATP/NADPH balancing mechanisms (cyclic and non-cyclic alternative electron transport), and regulation of Rubisco activity, leads to emergent behaviors that may affect the operation and regulation of photosynthesis under different dynamic environmental conditions. The model was parameterized with experimental results in the literature, with a focus on Arabidopsis thaliana...
September 18, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28922956/dmts-is-an-effective-treatment-in-both-inhalation-and-injection-models-for-cyanide-poisoning-using-unanesthetized-mice
#8
Susan M DeLeon, Jason D Downey, Diane M Hildenberger, Melissa O Rhoomes, Lamont Booker, Gary A Rockwood, Kelly A Basi
CONTEXT: Cyanide (CN) is a metabolic poison, halting ATP synthesis by inhibiting complex IV of the electron transport chain. If exposed at high enough concentrations, humans and most animals can die within minutes. Because time is a crucial factor in survival of CN poisoning, a rapidly bioavailable, nontoxic, easy to administer CN medical countermeasure could improve morbidity/mortality in a mass CN exposure scenario. The most likely route of exposure to CN is via inhalation. OBJECTIVE: This study examined the efficacy of a new formulation for dimethyl trisulfide (DMTS), a countermeasure which has shown promise as a treatment for CN poisoning, using both inhalation and injection models of CN exposure...
September 19, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28919040/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#9
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs...
August 29, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28918598/triacsin-c-reduces-lipid-droplet-formation-and-induces-mitochondrial-biogenesis-in-primary-rat-hepatocytes
#10
Carlos R P Dechandt, Felippe H Zuccolotto-Dos-Reis, Bruno G Teodoro, Anna Maria A P Fernandes, Marcos N Eberlin, Isis C Kettelhut, Carlos Curti, Luciane C Alberici
Intracellular long-chain acyl-CoA synthetases (ACSL) activate fatty acids to produce acyl-CoA, which undergoes β-oxidation and participates in the synthesis of esterified lipids such as triacylglycerol (TAG). Imbalances in these metabolic routes are closely associated with the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Triacsin C is one of the few compounds that inhibit TAG accumulation into lipid droplets (LD) by suppressing ACSL activity. Here we report that treatment of primary rat hepatocytes with triacsin C at concentrations lower than the IC50 (4...
September 16, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28918354/indium-iii-induces-isolated-mitochondrial-permeability-transition-by-inhibiting-proton-influx-and-triggering-oxidative-stress
#11
Lian Yuan, Jiaqi Zhang, Yujiao Liu, Jie Zhao, Fenglei Jiang, Yi Liu
While Indium's toxicity to organs is realized, its effects on mitochondria are still under investigation. Mitochondrial permeability transition (MPT) is widely accepted in mitochondrial dysfunction approaches and its importance in metal-induced mitochondrial degradation has been proposed. Since mitochondria are respiratory organelles, their interaction with free In(3+) is analyzed to access structural and functional changes. Spectral methods and multimode plate reader was used to detect mitochondrial swelling, membrane potential, membrane fluidity, and inner membrane permeability...
September 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28916541/a-proteomic-atlas-of-insulin-signalling-reveals-tissue-specific-mechanisms-of-longevity-assurance
#12
Luke S Tain, Robert Sehlke, Chirag Jain, Manopriya Chokkalingam, Nagarjuna Nagaraj, Paul Essers, Mark Rassner, Sebastian Grönke, Jenny Froelich, Christoph Dieterich, Matthias Mann, Nazif Alic, Andreas Beyer, Linda Partridge
Lowered activity of the insulin/IGF signalling (IIS) network can ameliorate the effects of ageing in laboratory animals and, possibly, humans. Although transcriptome remodelling in long-lived IIS mutants has been extensively documented, the causal mechanisms contributing to extended lifespan, particularly in specific tissues, remain unclear. We have characterized the proteomes of four key insulin-sensitive tissues in a long-lived Drosophila IIS mutant and control, and detected 44% of the predicted proteome (6,085 proteins)...
September 15, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28916229/japanese-leigh-syndrome-case-treated-with-epi-743
#13
Takeshi Kouga, Mariko Takagi, Akihiko Miyauchi, Hiroko Shimbo, Mizue Iai, Sumimasa Yamashita, Kei Murayama, Matthew B Klein, Guy Miller, Tomohide Goto, Hitoshi Osaka
BACKGROUND: Leigh syndrome is a mitochondrial disease caused by respiratory chain deficiency, and there are no proven effective therapies. EPI-743 is a potent cellular oxidative stress protectant and results of clinical trials for mitochondrial diseases are accumulating. CASE: At 5months, a girl presented with the scarce eye movement and diminished muscle tone. She was diagnosed with Leigh encephalopathy from blood and cerebrospinal fluid lactate elevation and MRI findings...
September 12, 2017: Brain & Development
https://www.readbyqxmd.com/read/28903070/role-of-the-ampk-pathway-in-promoting-autophagic-flux-via-modulating-mitochondrial-dynamics-in-neurodegenerative-diseases-insight-into-prion-diseases
#14
REVIEW
Syed Zahid Ali Shah, Deming Zhao, Tariq Hussain, Lifeng Yang
Neurons are highly energy demanding cells dependent on the mitochondrial oxidative phosphorylation system. Mitochondria generate energy via respiratory complexes that constitute the electron transport chain. Adenosine triphosphate depletion or glucose starvation act as a trigger for the activation of adenosine monophosphate-activated protein kinase (AMPK). AMPK is an evolutionarily conserved protein that plays an important role in cell survival and organismal longevity through modulation of energy homeostasis and autophagy...
September 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28900834/coq10-increases-mitochondrial-mass-and-polarization-atp-and-oct4-potency-levels-and-bovine-oocyte-mii-during-ivm-while-decreasing-ampk-activity-and-oocyte-death
#15
M K Abdulhasan, Q Li, J Dai, H M Abu-Soud, E E Puscheck, D A Rappolee
PURPOSE: We tested whether mitochondrial electron transport chain electron carrier coenzyme Q10 (CoQ10) increases ATP during bovine IVM and increases %M2 oocytes, mitochondrial polarization/mass, and Oct4, and decreases pAMPK and oocyte death. METHODS: Bovine oocytes were aspirated from ovaries and cultured in IVM media for 24 h with 0, 20, 40, or 60 μM CoQ10. Oocytes were assayed for ATP by luciferase-based luminescence. Oocyte micrographs were quantitated for Oct4, pAMPK (i...
September 12, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28892387/functionalized-poly-3-4-ethylenedioxy-bithiophene-films-for-tuning-electrochromic-and-thermoelectric-properties
#16
Yongjing Hu, Xiaofang Liu, Fengxing Jiang, Weiqiang Zhou, Congcong Liu, Xuemin Duan, Jingkun Xu
Conductive thiophene-base polymers have gained great concern in the organic electron materials such as electrochromic and thermoelectric materials. However, they suffer from poor electron transport property and long-term stability leading to the limited development eventually. Here, we proposed a strategy of functionalized thiophene-based polymers with oligo(ethylene glycol) or alkyl side chains and synthesized a series of poly(3,4-ethylenedioxy bithiophene)s (PEDTs) to tune their electrochromic and thermoelectric properties...
September 11, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28892295/transcriptome-and-proteome-dynamics-in-chemostat-culture-reveal-how-campylobacter-jejuni-modulates-metabolism-stress-responses-and-virulence-factors-upon-changes-in-oxygen-availability
#17
Edward J Guccione, John J Kendall, Andrew Hitchcock, Nitanshu Garg, Michael A White, Francis Mulholland, Robert K Poole, David J Kelly
Campylobacter jejuni, the most frequent cause of food-borne bacterial gastroenteritis worldwide, is a microaerophile that has to survive high environmental oxygen tensions, adapt to oxygen limitation in the intestine and resist host oxidative attack. Here, oxygen-dependent changes in C. jejuni physiology were studied at constant growth rate using carbon (serine)-limited continuous chemostat cultures. We show that a perceived aerobiosis scale can be calibrated by the acetate excretion flux, which becomes zero when metabolism is fully aerobic (100% aerobiosis)...
September 11, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28890369/selenium-incorporated-guar-gum-nanoparticles-safeguards-mitochondrial-bioenergetics-during-ischemia-reperfusion-injury-in-h9c2-cardiac-cells
#18
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/28890186/ionophores-at-work-exploring-the-interaction-of-guanosine-based-amphiphiles-with-phospholipid-membranes
#19
Giuseppe Vitiello, Domenica Musumeci, Alexandros Koutsioubas, Luigi Paduano, Daniela Montesarchio, Gerardino D'Errico
An amphiphilic derivative of guanosine, carrying a myristoyl group at the 5'-position and two methoxy(triethylene glycol) appendages at the 2' and 3'-positions (1), endowed with high ionophoric activity, has been here studied in its interaction mode with a model lipid membrane along with its 5'-spin-labelled analogue 2, bearing the 5-doxyl-stearic in lieu of the myristic residue. Electron spin resonance spectra, carried out on the spin-labelled nucleolipid 2 in mixture with a DOPC/DOPG phospholipid bilayer, on one side, and on spin-labelled lipids mixed with 1, on the other, integrated with dynamic light scattering and neutron reflectivity measurements, allowed getting an in-depth picture of the effect of the ionophores on membrane structure, relevant to clarify the ion transport mechanism through lipid bilayers...
September 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28885844/synthesis-and-c-h-functionalization-chemistry-of-thiazole-semicoronenediimides-tscdis-and-coronenediimides-tcdis
#20
Qinqin Shi, Eric S Andreansky, Seth R Marder, Simon B Blakey
Coronenediimide (CDI) derivatives have a planar structure, a reasonably high electron affinity, and a rigid and extended delocalized π-system. Therefore, this core and variants thereof may be promising building blocks for the synthesis of electron transport materials. Herein, we have synthesized thiazole-semicoronenediimides (TsCDIs) and -coronenediimides (TCDIs) by a two-step process from a perylenediimide (PDI) precursor. Conditions for C-H arylation and heteroarylation of the thiazole moiety of this core were developed and were successfully used for the synthesis of dimer, triad, and polymeric materials...
September 8, 2017: Journal of Organic Chemistry
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