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Bioenergetics

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https://www.readbyqxmd.com/read/28538623/impact-of-a-novel-pi3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#1
George E Black, Kyle K Sokol, Donald M Moe, Jon Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhalo 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 PI3-kinase 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) METHODS: 16 swine were studied using LY294002 (LY), a non-selective PI3-KI: Animals were assigned to Trauma only (TO, N=3); LY drug only (LYO, N=3); and Experimental (N=10), trauma + drug (LY+T) groups...
May 22, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28538163/metabolic-signatures-of-t-cells-and-macrophages-in-rheumatoid-arthritis
#2
REVIEW
Cornelia M Weyand, Markus Zeisbrich, Jörg J Goronzy
In most autoimmune diseases, a decade-long defect in self-tolerance eventually leads to clinically relevant, tissue-destructive inflammatory disease. The pathogenic potential of chronic persistent immune responses during the pre-clinical and clinical phase is ultimately linked to the bioenergetic fitness of innate and adaptive immune cells. Chronic immune cell stimulation, high cellular turn-over, structural damage to the host tissue and maladaptive wound healing, all require a reliable supply of nutrients, oxygen, and biosynthetic precursors...
May 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28533437/metformin-inhibits-cellular-proliferation-and-bioenergetics-in-colorectal-cancer-patient-derived-xenografts
#3
Nur-Afidah Mohamed Suhaimi, Wai Min Phyo, Hao Yun Yap, Sharon Heng Yee Choy, Xiaona Wei, Yukti Choudhury, Wai Jin Tan, Luke Anthony Peng Yee Tan, Roger Sik Yin Foo, Suzanne Hui San Tan, Zenia Tiang, Chin Fong Wong, Poh Koon Koh, Min-Han Tan
There is increasing pre-clinical evidence suggesting that metformin, an anti-diabetic drug, has anti-cancer properties against various malignancies including colorectal cancer (CRC). However, majority of evidence which were derived from cancer cell lines and xenografts are likely to overestimate the benefit of metformin since these models are inadequate and require supraphysiological levels of metformin. Here, we generated patient-derived xenografts (PDX) lines from 2 CRC patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for CRC...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28533227/detecting-the-presence-and-progression-of-premalignant-lung-lesions-via-airway-gene-expression
#4
Jennifer Beane, Sarah A Mazzilli, Anna M Tassinari, Gang Liu, Xiaohui Zhang, Hanqiao Liu, Anne Dy Buncio, Samjot S Dhillon, Suso J Platero, Marc E Lenburg, Mary E Reid, Stephen Lam, Avrum E Spira
  Lung cancer (LC) is the leading cause of cancer death in the US. The molecular events preceding the onset of disease are poorly understood and no effective tools exist to identify smokers with premalignant lesions (PMLs) that will progress to invasive cancer. Prior work identified molecular alterations in the smoke-exposed airway field of injury associated with LC.  Here we focus on an earlier stage in the disease process leveraging the airway field of injury to study PMLs and its utility in LC chemoprevention...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28533168/prospects-for-therapeutic-mitochondrial-transplantation
#5
REVIEW
Jenna L Gollihue, Alexander G Rabchevsky
Mitochondrial dysfunction has been implicated in a multitude of diseases and pathological conditions- the organelles that are essential for life can also be major players in contributing to cell death and disease. Because mitochondria are so well established in our existence, being present in all cell types except for red blood cells and having the responsibility of providing most of our energy needs for survival, then dysfunctional mitochondria can elicit devastating cellular pathologies that can be widespread across the entire organism...
May 19, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28527631/the-thiol-switch-c684-in-mitofusin-2-mediates-redox-induced-alterations-of-mitochondrial-shape-and-respiration
#6
Osamah Thaher, Christina Wolf, Partha Narayan Dey, Alireza Pouya, Verena Wüllner, Stefan Tenzer, Axel Methner
Mitofusin-2 (MFN2) is a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. MFN2 also plays a role in mitochondrial fusion induced by changes in the intracellular redox state. Adding oxidized glutathione (GSSG), the core cellular stress indicator, to mitochondrial preparations stimulates mitochondrial fusion by inducing disulphide bond-mediated oligomer formation of MFN2 and its homolog MFN1 which involve cysteine 684 (C684) of MFN2. Mitochondrial hyperfusion represents an adaptive stress response that confers transient protection by increasing mitochondrial ATP production but how this depends on the thiol switch C684 in MFN2 has not been investigated...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28527566/abnormalities-in-high-energy-phosphate-metabolism-in-first-episode-bipolar-disorder-measured-using-31-p-magnetic-resonance-spectroscopy
#7
Fei Du, Cagri Yuksel, Virginie-Anne Chouinard, Polly Huynh, Kyle Ryan, Bruce M Cohen, Dost Öngür
BACKGROUND: Brain energy metabolism is critical for supporting synaptic function and information processing. A growing body of evidence suggests abnormalities in brain bioenergetics in psychiatric disorders, including both bipolar disorder (BD) and schizophrenia. (31)P magnetic resonance spectroscopy provides a noninvasive window into these processes in vivo. Using this approach, we previously showed that patients with BD show normal adenosine triphosphate (ATP) and phosphocreatine levels at rest but cannot maintain normal ATP levels in the visual cortex during times of high energy demand (photic stimulation)...
April 7, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28526246/impaired-mitophagy-facilitates-mitochondrial-damage-in-danon-disease
#8
Sherin I Hashem, Anne N Murphy, Ajit S Divakaruni, Matthew L Klos, Bradley C Nelson, Emily C Gault, Teisha J Rowland, Cynthia N Perry, Yusu Gu, Nancy D Dalton, William H Bradford, Eric J Devaney, Kirk L Peterson, Kenneth L Jones, Matthew R G Taylor, Ju Chen, Neil C Chi, Eric D Adler
RATIONALE: Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis...
May 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28516063/modulation-of-ca-2-signaling-by-anti-apoptotic-b-cell-lymphoma-2-proteins-at-the-endoplasmic-reticulum-mitochondrial-interface
#9
REVIEW
Tim Vervliet, Eva Clerix, Bruno Seitaj, Hristina Ivanova, Giovanni Monaco, Geert Bultynck
Mitochondria are important regulators of cell death and cell survival. Mitochondrial Ca(2+) levels are critically involved in both of these processes. On the one hand, excessive mitochondrial Ca(2+) leads to Ca(2+)-induced mitochondrial outer membrane permeabilization and thus apoptosis. On the other hand, mitochondria need Ca(2+) in order to efficiently fuel the tricarboxylic acid cycle and maintain adequate mitochondrial bioenergetics. For obtaining this Ca(2+), the mitochondria are largely dependent on close contact sites with the endoplasmic reticulum (ER), the so-called mitochondria-associated ER membranes...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28515225/energy-metabolic-pathways-control-the-fate-and-function-of-myeloid-immune-cells
#10
REVIEW
Amir A Al-Khami, Paulo C Rodriguez, Augusto C Ochoa
The past decade has seen a significant interest in investigating the intracellular metabolism of cells of the immune system. This has increased the realization that immune cells endure metabolic reprogramming upon responding to pathogen-derived or inflammatory signals. More importantly, not only does this metabolic switch provide for the bioenergetic and biosynthetic demands but also it, in a highly specific manner, determines the cellular fate and function. In this review, we discuss the metabolic aspects that regulate the differentiation and function of myeloid cells, pivotal for both innate and adaptive immunity...
May 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28515169/osmoregulation-bioenergetics-and-oxidative-stress-in-coastal-marine-invertebrates-raising-the-questions-for-future-research
#11
REVIEW
Georgina A Rivera-Ingraham, Jehan-Hervé Lignot
Osmoregulation is by no means an energetically cheap process, and its costs have been extensively quantified in terms of respiration and aerobic metabolism. Common products of mitochondrial activity are reactive oxygen and nitrogen species, which may cause oxidative stress by degrading key cell components, while playing essential roles in cell homeostasis. Given the delicate equilibrium between pro- and antioxidants in fueling acclimation responses, the need for a thorough understanding of the relationship between salinity-induced oxidative stress and osmoregulation arises as an important issue, especially in the context of global changes and anthropogenic impacts on coastal habitats...
May 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28514673/metabolic-and-epigenetic-coordination-of-t-cell-and-macrophage-immunity
#12
REVIEW
Anthony T Phan, Ananda W Goldrath, Christopher K Glass
Recognition of pathogens by innate and adaptive immune cells instructs rapid alterations of cellular processes to promote effective resolution of infection. To accommodate increased bioenergetic and biosynthetic demands, metabolic pathways are harnessed to maximize proliferation and effector molecule production. In parallel, activation initiates context-specific gene-expression programs that drive effector functions and cell fates that correlate with changes in epigenetic landscapes. Many chromatin- and DNA-modifying enzymes make use of substrates and cofactors that are intermediates of metabolic pathways, providing potential cross talk between metabolism and epigenetic regulation of gene expression...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28514599/a-bioenergetics-systems-evaluation-of-ketogenic-diet-liver-effects
#13
Lewis J Hutfles, Heather M Wilkins, Scott J Koppel, Ian W Weidling, J Eva Selfridge, Eephie Tan, John P Thyfault, Chad Slawson, Aron W Fenton, Hao Zhu, Russell H Swerdlow
Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for one month on a ketogenic or standard chow diet. Compared to the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered...
May 17, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28513539/the-interplay-between-oncogenic-signaling-networks-and-mitochondrial-dynamics
#14
REVIEW
Sarbajeet Nagdas, David F Kashatus
Mitochondria are dynamic organelles that alter their organization in response to a variety of cellular cues. Mitochondria are central in many biologic processes, such as cellular bioenergetics and apoptosis, and mitochondrial network morphology can contribute to those physiologic processes. Some of the biologic processes that are in part governed by mitochondria are also commonly deregulated in cancers. Furthermore, patient tumor samples from a variety of cancers have revealed that mitochondrial dynamics machinery may be deregulated in tumors...
May 17, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28511992/rna-seq-analyses-reveal-that-cervical-spinal-cords-and-anterior-motor-neurons-from-amyotrophic-lateral-sclerosis-subjects-show-reduced-expression-of-mitochondrial-dna-encoded-respiratory-genes-and-rhtfam-may-correct-this-respiratory-deficiency
#15
Amy C Ladd, David G Brohawn, Ravindar R Thomas, Paula M Keeney, Stuart S Berr, Shaharyar M Khan, Francisco R Portell, Meiram Zh Shakenov, Patrick F Antkowiak, Bijoy Kundu, Nicholas Tustison, James P Bennett
Amyotrophic lateral sclerosis (ALS) is a generally fatal neurodegenerative disease of adults that produces weakness and atrophy due to dysfunction and death of upper and lower motor neurons. We used RNA-sequencing (RNA-seq) to analyze expression of all mitochondrial DNA (mtDNA)-encoded respiratory genes in ALS and CTL human cervical spinal cords (hCSC) and isolated motor neurons. We analyzed with RNA-seq mtDNA gene expression in human neural stem cells (hNSC) exposed to recombinant human mitochondrial transcription factor A (rhTFAM), visualized in 3-dimensions clustered gene networks activated by rhTFAM, quantitated their interactions with other genes and determined their gene ontology (GO) families...
May 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28511867/social-housing-and-social-isolation-impact-on-stress-indices-and-energy-balance-in-male-and-female-syrian-hamsters-mesocricetus-auratus
#16
Amy P Ross, Alisa Norvelle, Dennis C Choi, James C Walton, H Elliott Albers, Kim L Huhman
Although Syrian hamsters are thought to be naturally solitary, recent evidence from our laboratory demonstrates that hamsters may actually prefer social contact. Hamsters increase their preference for a location associated with an agonistic encounter regardless of whether they have "won" or "lost". It has also been reported that social housing as well as exposure to intermittent social defeat or to a brief footshock stressor increase food intake and body mass in hamsters. By contrast, it has also been suggested that housing hamsters in social isolation causes anxiety-induced anorexia and reductions in body mass selectively in females...
May 13, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28508041/mitochondrial-protein-linked-dna-breaks-perturb-mitochondrial-gene-transcription-and-trigger-free-radical-induced-dna-damage
#17
Shih-Chieh Chiang, Martin Meagher, Nick Kassouf, Majid Hafezparast, Peter J McKinnon, Rachel Haywood, Sherif F El-Khamisy
Breakage of one strand of DNA is the most common form of DNA damage. Most damaged DNA termini require end-processing in preparation for ligation. The importance of this step is highlighted by the association of defects in the 3'-end processing enzyme tyrosyl DNA phosphodiesterase 1 (TDP1) and neurodegeneration and by the cytotoxic induction of protein-linked DNA breaks (PDBs) and oxidized nucleic acid intermediates during chemotherapy and radiotherapy. Although much is known about the repair of PDBs in the nucleus, little is known about this process in the mitochondria...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28507561/deletion-extents-are-not-the-cause-of-clinical-variability-in-22q11-2-deletion-syndrome-does-the-interaction-between-dgcr8-and-mirna-cnvs-play-a-major-role
#18
Veronica Bertini, Alessia Azzarà, Annalisa Legitimo, Roberta Milone, Roberta Battini, Rita Consolini, Angelo Valetto
In humans, the most common genomic disorder is the hemizygous deletion of the chromosome 22q11.2 region, that results in the "22q11.2 deletion syndrome" (22q11.2DS). A peculiarity of 22q11.2DS is its great phenotypic variability that makes this pathology a classic example of a syndrome with variable expressivity and incomplete penetrance. The reasons for this variability have not been elucidated yet, and the molecular substrates underlying the different clinical features of 22q11.2DS are still debated. A cohort of 21 patients has been analyzed by array CGH in order to detect some of the genetic differences that may influence this variability...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28507012/dietary-factors-promoting-brown-and-beige-fat-development-and-thermogenesis
#19
REVIEW
Meshail Okla, Jiyoung Kim, Karsten Koehler, Soonkyu Chung
Brown adipose tissue (BAT) is a specialized fat tissue that has a high capacity to dissociate cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Adult humans possess a substantial amount of BAT in the form of constitutively active brown fat or inducible beige fat. BAT activity in humans is inversely correlated with adiposity, blood glucose concentrations, and insulin sensitivity; this suggests that strategies aimed at BAT-mediated bioenergetics are an attractive therapeutic target in combating the continuing epidemic of obesity and diabetes...
May 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28505224/muscle-bioenergetic-considerations-for-intrinsic-laryngeal-skeletal-muscle-physiology
#20
Mary J Sandage, Audrey G Smith
Purpose: Intrinsic laryngeal skeletal muscle bioenergetics, the means by which muscles produce fuel for muscle metabolism, is an understudied aspect of laryngeal physiology with direct implications for voice habilitation and rehabilitation. The purpose of this review is to describe bioenergetic pathways identified in limb skeletal muscle and introduce bioenergetic physiology as a necessary parameter for theoretical models of laryngeal skeletal muscle function. Method: A comprehensive review of the human intrinsic laryngeal skeletal muscle physiology literature was conducted...
May 24, 2017: Journal of Speech, Language, and Hearing Research: JSLHR
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