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https://www.readbyqxmd.com/read/28936802/significance-of-mitochondrial-protein-post-translational-modifications-in-pathophysiology-of-brain-injury
#1
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/28936218/atoma1-affects-the-oxphos-system-and-plant-growth-in-contrast-to-other-newly-identified-atp-independent-proteases-in-arabidopsis-mitochondria
#2
Iwona Migdal, Renata Skibior-Blaszczyk, Malgorzata Heidorn-Czarna, Marta Kolodziejczak, Arnold Garbiec, Hanna Janska
Compared with yeast, our knowledge on members of the ATP-independent plant mitochondrial proteolytic machinery is rather poor. In the present study, using confocal microscopy and immunoblotting, we proved that homologs of yeast Oma1, Atp23, Imp1, Imp2, and Oct1 proteases are localized in Arabidopsis mitochondria. We characterized these components of the ATP-independent proteolytic system as well as the earlier identified protease, AtICP55, with an emphasis on their significance in plant growth and functionality in the OXPHOS system...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28935892/bioenergetic-state-regulates-innate-inflammatory-responses-through-the-transcriptional-co-repressor-ctbp
#3
Yiguo Shen, David Kapfhamer, Angela M Minnella, Ji-Eun Kim, Seok Joon Won, Yanting Chen, Yong Huang, Ley Hian Low, Stephen M Massa, Raymond A Swanson
The innate inflammatory response contributes to secondary injury in brain trauma and other disorders. Metabolic factors such as caloric restriction, ketogenic diet, and hyperglycemia influence the inflammatory response, but how this occurs is unclear. Here, we show that glucose metabolism regulates pro-inflammatory NF-κB transcriptional activity through effects on the cytosolic NADH:NAD(+) ratio and the NAD(H) sensitive transcriptional co-repressor CtBP. Reduced glucose availability reduces the NADH:NAD(+) ratio, NF-κB transcriptional activity, and pro-inflammatory gene expression in macrophages and microglia...
September 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28935446/mitochondrial-adaptation-in-steatotic-mice
#4
Claudia Einer, Simon Hohenester, Ralf Wimmer, Lena Wottke, Renate Artmann, Sabine Schulz, Christian Gosmann, Alisha Simmons, Christin Leitzinger, Carola Eberhagen, Sabine Borchard, Sabine Schmitt, Stefanie M Hauck, Christine von Toerne, Martin Jastroch, Ellen Walheim, Christian Rust, Alexander L Gerbes, Bastian Popper, Doris Mayr, Max Schnurr, Angelika M Vollmar, Gerald Denk, Hans Zischka
Western lifestyle-associated malnutrition causes steatosis that may progress to liver inflammation and mitochondrial dysfunction has been suggested as a key factor in promoting this disease. Here we have molecularly, biochemically and biophysically analyzed mitochondria from steatotic wild type and immune-compromised mice fed a Western diet (WD) - enriched in saturated fatty acids (SFAs). WD-mitochondria demonstrated lipidomic changes, a decreased mitochondrial ATP production capacity and a significant sensitivity to calcium...
September 18, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28932194/h2s-induced-sulfhydration-biological-function-and-detection-methodology
#5
REVIEW
Da Zhang, Junbao Du, Chaoshu Tang, Yaqian Huang, Hongfang Jin
At appropriate concentrations, hydrogen sulfide, a well-known gasotransmitter, plays important roles in both physiology and pathophysiology. Increasing evidence suggests that modifying thiol groups of specific cysteines in target proteins via sulfhydration or persulfidation is one of the important mechanisms responsible for the biological functions of hydrogen sulfide. A variety of key proteins of different cellular pathways in mammals have been reported to be sulfhydrated by hydrogen sulfide to participate and regulate the processes of cell survival/death, cell differentiation, cell proliferation/hypertrophy, cellular metabolism, mitochondrial bioenergetics/biogenesis, endoplasmic reticulum stress, vasorelaxtion, inflammation, oxidative stress, etc...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28932034/alteration-of-cellular-metabolism-in-cancer-cells-and-its-therapeutic-prospects
#6
REVIEW
Biranchi Narayan Biswal, Surya Narayan Das, Bijoy Kumar Das, Rachna Rath
Transformation of a normal cell into a cancerous phenotype is essentially backed by genetic mutations that trigger several oncogenic signaling pathways. These signaling pathways rewire the cellular metabolism to meet the bioenergetic and biomass requirement of proliferating cell, which is different from a quiescent cell. Although the change of metabolism in a cancer cell was observed and studied in the mid-20(th) century, it was not adequate to explain oncogenesis. Now, equipped with a revolution of oncogenes, we have a genetic basis to explain the transformation...
May 2017: Journal of Oral and Maxillofacial Pathology: JOMFP
https://www.readbyqxmd.com/read/28931599/mrpl35-a-mitospecific-component-of-mitoribosomes-plays-a-key-role-in-cytochrome-c-oxidase-assembly
#7
Jodie M Box, Jasvinder Kaur, Rosemary A Stuart
Mitoribosomes perform the synthesis of the core components of the oxidative phosphorylation (OXPHOS) system encoded by the mitochondrial genome. We provide evidence that MrpL35 (mL38), a mitospecific component of the yeast mitoribosomal central protuberance, assembles into a subcomplex with MrpL7 (uL5), Mrp7 (bL27) and MrpL36 (bL31) and mitospecific proteins MrpL17 (mL46) and MrpL28 (mL40). We isolated respiratory defective mrpL35 mutant yeast strains, which do not display an overall inhibition in mitochondrial protein synthesis, but rather have a problem in cytochrome c oxidase complex (COX) assembly...
September 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28931570/mitochondrial-dna-double-strand-breaks-in-oligodendrocytes-cause-demyelination-axonal-injury-and-cns-inflammation
#8
Pernille M Madsen, Milena Pinto, Shreyans Patel, Stephanie McCarthy, Han Gao, Mehran Taherian, Shaffiat Karmally, Claudia V Pereira, Galina Dvoriantchikova, Dmitry Ivanov, Kenji F Tanaka, Carlos T Moraes, Roberta Brambilla
Mitochondrial dysfunction has been implicated in the pathophysiology of neurodegenerative disorders, including multiple sclerosis (MS). To date, the investigation of mitochondrial dysfunction in MS has focused exclusively on neurons, with no studies exploring whether dysregulation of mitochondrial bioenergetics and/or genetics in oligodendrocytes might be associated with the etiopathogenesis of MS and other demyelinating syndromes. To address this question, we established a mouse model where mitochondrial DNA (mtDNA) double-strand breaks (DSB) were specifically induced in myelinating oligodendrocytes (PLP:mtPstI mice) by expressing a mitochondrial-targeted endonuclease, mtPstI, starting at 3 weeks of age...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28930961/impact-of-a-novel-phosphoinositol-3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#9
George Edward Black, Kyle K Sokol, Donald M Moe, Jon D Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhaylo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental phosphoinositol-3 kinase (PI3-K) inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage-associated molecular patterns (DAMPs)...
October 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28927964/behavioral-responses-of-beluga-whales-delphinapterus-leucas-to-environmental-variation-in-an-arctic-estuary
#10
Paul A Anderson, Russell B Poe, Laura A Thompson, Nansen Weber, Tracy A Romano
Some Arctic estuaries serve as substrate rubbing sites for beluga whales (Delphinapterus leucas) in the summer, representing a specialized resource for the species. Understanding how environmental variation affects the species' behavior is essential to management of these habitats in coming years as the climate changes. Spatiotemporal and environmental variables were recorded for behavioral observations, during which focal groups of whales in an estuary were video-recorded for enumeration and behavioral analysis...
September 16, 2017: Behavioural Processes
https://www.readbyqxmd.com/read/28925557/analysis-of-multiple-haloarchaeal-genomes-suggests-that-the-quinone-dependent-respiratory-nitric-oxide-reductase-is-an-important-source-of-nitrous-oxide-in-hypersaline-environments
#11
Javier Torregrosa-Crespo, Pedro González-Torres, Vanesa Bautista, Julia M Esclapez, Carmen Pire, Mónica Camacho, María José Bonete, David J Richardson, Nicholas J Watmough, Rosa María Martínez-Espinosa
Microorganisms, including Bacteria and Archaea, play a key role in denitrification, which is the major mechanism by which fixed nitrogen returns to the atmosphere from soil and water. Whilst the enzymology of denitrification is well understood in Bacteria, the details of the last two reactions in this pathway, which catalyse the reduction of nitric oxide (NO) via nitrous oxide (N2 O) to nitrogen (N2 ), are little studied in Archaea, and hardly at all in haloarchaea. This work describes an extensive interspecies analysis of both complete and draft haloarchaeal genomes aimed at identifying the genes that encode respiratory nitric oxide reductases (Nors)...
September 19, 2017: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/28925102/continued-alcohol-misuse-in-human-cirrhosis-is-associated-with-an-impaired-gut-liver-axis
#12
Jasmohan S Bajaj, Genta Kakiyama, Derrick Zhao, Hajime Takei, Andrew Fagan, Phillip Hylemon, Huiping Zhou, William M Pandak, Hiroshi Nittono, Oliver Fiehn, Nita Salzman, Mary Holtz, Pippa Simpson, Edith A Gavis, Douglas M Heuman, Runping Liu, Dae Joong Kang, Masoumeh Sikaroodi, Patrick M Gillevet
BACKGROUND: Cirrhosis and alcohol can independently affect the gut-liver axis with systemic inflammation. However their concurrent impact in humans is unclear. AIM: Determine the effect of continued alcohol misuse on the gut-liver axis in cirrhotic patients. METHODS: Age and MELD-balanced cirrhotic patients who were currently drinking (Alc) or abstinent (NAlc), and healthy controls underwent serum and stool collection. A subset underwent upper endoscopy and colonoscopy for biopsies and duodenal fluid collection...
September 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28923861/mct1-inhibitor-azd3965-increases-mitochondrial-metabolism-facilitating-combination-therapy-and-non-invasive-magnetic-resonance-spectroscopy
#13
Mounia Beloueche-Babari, Slawomir Wantuch, Teresa Casals Galobart, Markela Koniordou, Harold G Parkes, Vaitha Arunan, Yuen-Li Chung, Thomas R Eykyn, Paul D Smith, Martin O Leach
Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo. Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923859/upregulation-of-cystathionine-%C3%AE-synthase-in-colonic-epithelia-reprograms-metabolism-and-promotes-carcinogenesis
#14
Ches'Nique M Phillips, John Zatarain, Michael E Nicholls, Craig Porter, Steve G Widen, Ketan Thanki, Paul Johnson, Muhammad U Jawad, Mary Pat Moyer, James W Randall, Judith L Hellmich, Manjit Maskey, Suimin Qiu, Thomas Wood, Nadiya Druzhyna, Bartosz Szczesny, Katalin Modis, Csaba Szabo, Celia Chao, Mark R Hellmich
The transsulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923556/de-novo-assembly-and-transcriptome-characterization-of-the-freshwater-prawn-palaemonetes-argentinus-implications-for-a-detoxification-response
#15
C Fernando García, Nicolas Pedrini, Arturo Sánchez-Paz, Carlos S Reyna-Blanco, Sabrina Lavarias, Adriana Muhlia-Almazán, Analía Fernández-Giménez, Aldana Laino, Enrique de-la-Re-Vega, German Lukaszewicz, Alonso A López-Zavala, Luis G Brieba, Michael F Criscitello, Jesús S Carrasco-Miranda, Karina D García-Orozco, Adrian Ochoa-Leyva, Enrique Rudiño-Piñera, Alejandro Sanchez-Flores, Rogerio R Sotelo-Mundo
Palaemonetes argentinus, an abundant freshwater prawn species in the northern and central region of Argentina, has been used as a bioindicator of environmental pollutants as it displays a very high sensitivity to pollutants exposure. Despite their extraordinary ecological relevance, a lack of genomic information has hindered a more thorough understanding of the molecular mechanisms potentially involved in detoxification processes of this species. Thus, transcriptomic profiling studies represent a promising approach to overcome the limitations imposed by the lack of extensive genomic resources for P...
September 8, 2017: Marine Genomics
https://www.readbyqxmd.com/read/28920697/n%C3%AE%C2%B5-and-o-acetylation-in-mycobacterium-tuberculosis-lineage-7-and-lineage-4-strains-proteins-involved-in-bioenergetics-virulence-and-antimicrobial-resistance-are-acetylated
#16
Alemayehu Godana Birhanu, Solomon Abebe Yimer, Carol Holm-Hansen, Gunnstein Norheim, Abraham Aseffa, Markos Abebe, Tone Tønjum
Increasing evidence demonstrates that lysine acetylation is involved in Mycobacterium tuberculosis (Mtb) virulence and pathogenesis. However, previous investigations in Mtb have only monitored acetylation at lysine residues using selected reference strains. We analyzed the global Nε- and O-acetylation of 3 Mtb isolates; 2 lineage 7 clinical isolates and the lineage 4 H37Rv reference strain. Quantitative acetylome analysis resulted in identification of 2490 class-I acetylation sites, among them 2349 O-acetylation and 141 Nε-acetylation sites, derived from 953 unique proteins...
September 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28919076/mitochondrial-priming-by-cd28
#17
Ramon I Klein Geltink, David O'Sullivan, Mauro Corrado, Anna Bremser, Michael D Buck, Joerg M Buescher, Elke Firat, Xuekai Zhu, Gabriele Niedermann, George Caputa, Beth Kelly, Ursula Warthorst, Anne Rensing-Ehl, Ryan L Kyle, Lana Vandersarren, Jonathan D Curtis, Annette E Patterson, Simon Lawless, Katarzyna Grzes, Jing Qiu, David E Sanin, Oliver Kretz, Tobias B Huber, Sophie Janssens, Bart N Lambrecht, Angelika S Rambold, Edward J Pearce, Erika L Pearce
T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand...
September 1, 2017: Cell
https://www.readbyqxmd.com/read/28918113/regulation-of-mitochondrial-bioenergetics-by-the-non-canonical-roles-of-mitochondrial-dynamics-proteins-in-the-heart
#18
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/28912578/tumour-acidosis-from-the-passenger-to-the-driver-s-seat
#19
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
https://www.readbyqxmd.com/read/28904018/dyslipidemia-impairs-mitochondrial-trafficking-and-function-in-sensory-neurons
#20
Amy E Rumora, Stephen I Lentz, Lucy M Hinder, Samuel W Jackson, Andrew Valesano, Gideon E Levinson, Eva L Feldman
Mitochondrial trafficking plays a central role in dorsal root ganglion (DRG) neuronal cell survival and neurotransmission by transporting mitochondria from the neuronal cell body throughout the bundles of DRG axons. In type 2 diabetes (T2DM), dyslipidemia and hyperglycemia damage DRG neurons and induce mitochondrial dysfunction; however, the impact of free fatty acids and glucose on mitochondrial trafficking in DRG neurons remains unknown. To evaluate the impact of free fatty acids compared to hyperglycemia on mitochondrial transport, primary adult mouse DRG neuron cultures were treated with physiologic concentrations of palmitate and glucose and assessed for alterations in mitochondrial trafficking, mitochondrial membrane potential, and mitochondrial bioenergetics...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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