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https://www.readbyqxmd.com/read/28942921/mitochondrial-fission-promotes-the-continued-clearance-of-apoptotic-cells-by-macrophages
#1
Ying Wang, Manikandan Subramanian, Arif Yurdagul, Valéria C Barbosa-Lorenzi, Bishuang Cai, Jaime de Juan-Sanz, Timothy A Ryan, Masatoshi Nomura, Frederick R Maxfield, Ira Tabas
Clearance of apoptotic cells (ACs) by phagocytes (efferocytosis) prevents post-apoptotic necrosis and dampens inflammation. Defective efferocytosis drives important diseases, including atherosclerosis. For efficient efferocytosis, phagocytes must be able to internalize multiple ACs. We show here that uptake of multiple ACs by macrophages requires dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, which is triggered by AC uptake. When mitochondrial fission is disabled, AC-induced increase in cytosolic calcium is blunted owing to mitochondrial calcium sequestration, and calcium-dependent phagosome formation around secondarily encountered ACs is impaired...
September 20, 2017: Cell
https://www.readbyqxmd.com/read/28942523/overexpression-of-plastidic-maize-nadp-malate-dehydrogenase-zmnadp-mdh-in-arabidopsis-thaliana-confers-tolerance-to-salt-stress
#2
Deepika Kandoi, Sasmita Mohanty, Baishnab C Tripathy
The plastidic C4 Zea mays NADP-malate dehydrogenase (ZmNADP-MDH), responsible for catalysis of oxaloacetate to malate, was overexpressed in Arabidopsis thaliana to assess its impact on photosynthesis and tolerance to salinity stress. Different transgenic lines were produced having ~3-6-fold higher MDH protein abundance and NADP-MDH enzyme activity than vector control. The overexpressors had similar chlorophyll, carotenoid, and protein content as that of vector control. Their photosynthetic electron transport rates, carbon assimilation rate, and consequently fresh weight and dry weight were almost similar...
September 24, 2017: Protoplasma
https://www.readbyqxmd.com/read/28942196/metformin-selectively-targets-redox-control-of-complex-i-energy-transduction
#3
Amy R Cameron, Lisa Logie, Kashyap Patel, Stefan Erhardt, Sandra Bacon, Paul Middleton, Jean Harthill, Calum Forteath, Josh T Coats, Calum Kerr, Heather Curry, Derek Stewart, Kei Sakamoto, Peter Repiščák, Martin J Paterson, Ilmo Hassinen, Gordon McDougall, Graham Rena
Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production...
August 26, 2017: Redox Biology
https://www.readbyqxmd.com/read/28939417/mitochondrial-metabolism-yin-and-yang-for-tumor-progression
#4
REVIEW
Lorea Valcarcel-Jimenez, Edoardo Gaude, Veronica Torrano, Christian Frezza, Arkaitz Carracedo
Altered metabolism is a distinct feature of cancer cells. During transformation, the entire metabolic network is rewired to efficiently convert nutrients to biosynthetic precursors to sustain cancer cell growth and proliferation. Whilst the molecular underpinnings of this metabolic reprogramming have been described, its role in tumor progression is still under investigation. Importantly, the mitochondrion is a central actor in many of the metabolic processes that are altered in tumors. Yet, we have only begun to understand the dualities of mitochondrial function during cancer metastasis and therapy resistance...
July 18, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28938972/mitochondrial-metabolism-yin-and-yang-for-tumor-progression
#5
REVIEW
Lorea Valcarcel-Jimenez, Edoardo Gaude, Veronica Torrano, Christian Frezza, Arkaitz Carracedo
Altered metabolism is a distinct feature of cancer cells. During transformation, the entire metabolic network is rewired to efficiently convert nutrients to biosynthetic precursors to sustain cancer cell growth and proliferation. Whilst the molecular underpinnings of this metabolic reprogramming have been described, its role in tumor progression is still under investigation. Importantly, the mitochondrion is a central actor in many of the metabolic processes that are altered in tumors. Yet, we have only begun to understand the dualities of mitochondrial function during cancer metastasis and therapy resistance...
October 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28936802/significance-of-mitochondrial-protein-post-translational-modifications-in-pathophysiology-of-brain-injury
#6
Nina Klimova, Aaron Long, Tibor Kristian
Mitochondria are complex organelles that undergo constant fusion and fission in order to adapt to the ever-changing cellular environment. The fusion/fission proteins, localized in the inner and outer mitochondrial membrane, play critical roles under pathological conditions such as acute brain injury and neurodegenerative diseases. Post-translational modifications of these proteins tightly regulate their function and activity, ultimately impacting mitochondrial dynamics and their efficiency to generate ATP. The individual post-translational modifications that are known to affect mitochondrial dynamics include SUMOylation, ubiquitination, phosphorylation, S-nitrosylation, acetylation, O-linked N-acetyl-glucosamine glycosylation, ADP-ribosylation, and proteolytic cleavage...
September 21, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28933367/targeting-metabolic-modulation-and-mitochondrial-dysfunction-in-the-treatment-of-heart-failure
#7
REVIEW
Abbey Steggall, Ify R Mordi, Chim C Lang
Despite significant improvements in morbidity and mortality with current evidence-based pharmaceutical-based treatment of heart failure (HF) over the previous decades, the burden of HF remains high. An alternative approach is currently being developed, which targets myocardial energy efficiency and the dysfunction of the cardiac mitochondria. Emerging evidence suggests that the insufficient availability of ATP to the failing myocardium can be attributed to abnormalities in the myocardial utilisation of its substrates rather than an overall lack of substrate availability...
May 10, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28928373/a-synthetic-cell-permeable-antioxidant-protects-neurons-against-acute-oxidative-stress
#8
Nicola J Drummond, Nick O Davies, Janet E Lovett, Mark R Miller, Graeme Cook, Thomas Becker, Catherina G Becker, Donald B McPhail, Tilo Kunath
Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson's disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927904/lipophilic-methylene-violet-analogues-as-modulators-of-mitochondrial-function-and-dysfunction
#9
Sandipan Roy Chowdhury, Omar M Khdour, Indrajit Bandyopadhyay, Sidney M Hecht
In an effort to identify methylene blue analogues having improved antioxidant activity, a series of new methylene violet analogues have been designed and synthesized. The analogues were prepared following a synthetic route that is more efficient than the previously reported methods, both in terms of yield and purity of the final products. The route involves the Smiles rearrangement as one of the crucial steps. Smiles rearrangement of suitably substituted diphenyl sulfide intermediates afforded the corresponding phenothiazine analogues in high yields, which were subsequently converted to the final products...
August 18, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28924186/interactome-analysis-reveals-znf804a-a-schizophrenia-risk-gene-as-a-novel-component-of-protein-translational-machinery-critical-for-embryonic-neurodevelopment
#10
Y Zhou, F Dong, T A Lanz, V Reinhart, M Li, L Liu, J Zou, H S Xi, Y Mao
Recent genome-wide association studies identified over 100 genetic loci that significantly associate with schizophrenia (SZ). A top candidate gene, ZNF804A, was robustly replicated in different populations. However, its neural functions are largely unknown. Here we show in mouse that ZFP804A, the homolog of ZNF804A, is required for normal progenitor proliferation and neuronal migration. Using a yeast two-hybrid genome-wide screen, we identified novel interacting proteins of ZNF804A. Rather than transcriptional factors, genes involved in mRNA translation are highly represented in our interactome result...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28923557/a-molecular-approach-towards-taxonomic-identification-of-elasmobranch-species-from-maltese-fisheries-landings
#11
Adriana Vella, Noel Vella, Sarah Schembri
The mitochondrial genome, through the application of DNA barcoding, provides a powerful tool for identifying species even when specimens are either incomplete or belong to species that exhibit cryptic diversity. In fisheries management accurate identification of whole or part of the specimens landed is a fundamental requirement for the conservation of species affected directly or indirectly by the fisheries activities. In this study cytochrome c oxidase subunit I (COI) and NADH dehydrogenase subunit 2 (ND2) sequences were used to genetically distinguish 36 elasmobranch species collected from Maltese (Central Mediterranean) commercial fisheries landings...
September 8, 2017: Marine Genomics
https://www.readbyqxmd.com/read/28923482/the-optimal-regulation-mode-of-bcl-2-apoptotic-switch-revealed-by-bistability-analysis
#12
Zhiyong Yin, Hong Qi, Lili Liu, Zhen Jin
In most cell types, apoptosis occurs by the mitochondrial outer membrane permeability (MOMP)-mediated pathway, which is controlled by Bcl-2 family proteins (often referred to as Bcl-2 apoptotic switch). These proteins, which display a range of bioactivities, can be divided into four types: effectors, inhibitors, activators and sensitizers. Although the complex interactions among Bcl-2 family members have been studied intensively, a unifying hypothesis for the mechanism they use to regulate MOMP remains elusive...
September 15, 2017: Bio Systems
https://www.readbyqxmd.com/read/28923249/akap-lbc-mediates-protection-against-doxorubicin-induced-cardiomyocyte-toxicity
#13
Stefania Caso, Darko Maric, Miroslav Arambasic, Susanna Cotecchia, Dario Diviani
Doxorubicin (DOX) is a chemotherapic agent that is widely used to treat hematological and solid tumors. Despite its efficacy, DOX displays significant cardiac toxicity associated with cardiomyocytes death and heart failure. Cardiac toxicity is mainly associated with the ability of DOX to alter mitochondrial function. The current lack of treatments to efficiently prevent DOX cardiotoxicity underscores the need of new therapeutic approaches. Our current findings show that stimulation of cardiomyocytes with the α1-adrenergic receptor (AR) agonist phenylephrine (PE) significantly inhibits the apoptotic effect of DOX...
September 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28920632/acute-cardiotoxicity-induced-by-doxorubicin-in-right-ventricle-is-associated-with-increase-of-oxidative-stress-and-apoptosis-in-rats
#14
N Anghel, H Herman, C Balta, M Rosu, M S Stan, D Nita, A Ivan, Z Galajda, A Ardelean, A Dinischiotu, A Hermenean
Doxorubicin (DOX) is one of the most effective chemotherapeutic agents, but its efficiency is seriously limited by the risk of developing cardiomyopathy. The most recognized cardiotoxic effect is left ventricular (LF) dysfunction, but MRI and echocardiography data demonstrated significant right ventricle (RV) function impairment. In order to clarify this aspect, the present study investigated the potential of DOX to induce acute RV cardiotoxicity at the same time as LV impairment. Rats were intraperitoneally (i...
September 18, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28919501/structural-and-kinetics-characterization-of-the-f1f0-atp-synthase-dimer-new-repercussion-of-monomer-monomer-contact
#15
Mercedes Esparza-Perusquía, Sofía Olvera-Sánchez, Juan Pablo Pardo, Guillermo Mendoza-Hernández, Federico Martínez, Oscar Flores-Herrera
Ustilago maydis is an aerobic basidiomycete that fully depends on oxidative phosphorylation for its supply of ATP, pointing to mitochondria as a key player in the energy metabolism of this organism. Mitochondrial F1F0-ATP synthase occurs in supramolecular structures. In this work, we isolated the monomer (640kDa) and the dimer (1280kDa) and characterized their subunit composition and kinetics of ATP hydrolysis. Mass spectrometry revealed that dimerizing subunits e and g were present in the dimer but not in the monomer...
September 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28918598/triacsin-c-reduces-lipid-droplet-formation-and-induces-mitochondrial-biogenesis-in-primary-rat-hepatocytes
#16
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/28918113/regulation-of-mitochondrial-bioenergetics-by-the-non-canonical-roles-of-mitochondrial-dynamics-proteins-in-the-heart
#17
REVIEW
Wang Wang, Celia Fernandez-Sanz, Shey-Shing Sheu
Recent advancement in mitochondrial research has significantly extended our knowledge on the role and regulation of mitochondria in health and disease. One important breakthrough is the delineation of how mitochondrial morphological changes, termed mitochondrial dynamics, are coupled to the bioenergetics and signaling functions of mitochondria. In general, it is believed that fusion leads to an increased mitochondrial respiration efficiency and resistance to stress-induced dysfunction while fission does the contrary...
September 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28918091/opposed-effects-of-dityrosine-formation-in-soluble-and-aggregated-%C3%AE-synuclein-on-fibril-growth
#18
Michael M Wördehoff, Hamed Shaykhalishahi, Luca Groß, Lothar Gremer, Matthias Stoldt, Alexander K Buell, Dieter Willbold, Wolfgang Hoyer
Parkinson's disease (PD) is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY)-crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from PD patients. Here we report that α-syn is highly susceptible to UV-induced DiY formation...
September 13, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28912602/kinetic-adaptation-of-human-myo19-for-active-mitochondrial-transport-to-growing-filopodia-tips
#19
Marko Ušaj, Arnon Henn
Myosins are actin-based molecular motors which are enzymatically adapted for their cellular functions such as transportation and membrane tethering. Human Myo19 affects mitochondrial motility, and promotes their localization to stress-induced filopodia. Therefore, studying Myo19 enzymology is essential to understand how this motor may facilitate mitochondrial motility. Towards this goal, we have purified Myo19 motor domain (Myo19-3IQ) from a human-cell expression system and utilized transient kinetics to study the Myo19-3IQ ATPase cycle...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912578/tumour-acidosis-from-the-passenger-to-the-driver-s-seat
#20
REVIEW
Cyril Corbet, Olivier Feron
The high metabolic demand of cancer cells leads to an accumulation of H(+) ions in the tumour microenvironment. The disorganized tumour vasculature prevents an efficient wash-out of H(+) ions released into the extracellular medium but also favours the development of tumour hypoxic regions associated with a shift towards glycolytic metabolism. Under hypoxia, the final balance of glycolysis, including breakdown of generated ATP, is the production of lactate and a stoichiometric amount of H(+) ions. Another major source of H(+) ions results from hydration of CO2 produced in the more oxidative tumour areas...
September 15, 2017: Nature Reviews. Cancer
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