13,461 results match your criteria atp synthase

Inhibitors of FFATP synthase enzymes for the treatment of tuberculosis and cancer.

William A Denny

Future Med Chem 2021 Apr 13. Epub 2021 Apr 13.

Auckland Cancer Society Research Centre, School of Medical Sciences, Private Bag 92019, Auckland, 1142, New Zealand.

The spectacular success of the mycobacterial FF-ATP synthase inhibitor bedaquiline for the treatment of drug-resistant tuberculosis has generated wide interest in the development of other inhibitors of this enzyme. Work in this realm has included close analogues of bedaquiline with better safety profiles and 'bedaquiline-like' compounds, some of which show potent antibacterial activity although none have yet progressed to clinical trials. The search has lately extended to a range of new scaffolds as potential inhibitors, including squaramides, diaminoquinazolines, chloroquinolines, dihydropyrazolo[1,5-a]pyrazin-4-ones, thiazolidinediones, diaminopyrimidines and tetrahydroquinolines. Read More

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Evaluating the mitochondrial activity and inflammatory state of dimethyl sulfoxide differentiated PLB-985 cells.

Mol Immunol 2021 Apr 7;135:1-11. Epub 2021 Apr 7.

Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada; New Brunswick Center for Precision Medicine, Moncton, NB, Canada. Electronic address:

Neutrophils play a key role in the innate immunity with their ability to generate and release inflammatory mediators that promote the inflammatory response and consequently restore the hemostasis. As active participants in several steps of the normal inflammatory response, neutrophils are also involved in chronic inflammatory diseases such as asthma, atherosclerosis, and arthritis. Given their dual role in the modulation of inflammation, regulating the inflammatory response of neutrophils has been suggested as an important therapeutic approach by numerous researchers. Read More

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MICOS and the mitochondrial inner membrane morphology - when things get out of shape.

FEBS Lett 2021 Apr 10. Epub 2021 Apr 10.

Department of Cellular Biochemistry, University Medical Center Göttingen, Humboldtallee 23, 37073, Göttingen, Germany.

Mitochondria play a key role in cellular signalling, metabolism and energetics. Proper architecture and remodelling of the inner mitochondrial membrane are essential for efficient respiration, apoptosis and quality control in the cell. Several protein complexes including mitochondrial contact site and cristae organising system (MICOS), F F -ATP synthase, and Optic Atrophy 1 (OPA1), facilitate formation, maintenance and stability of cristae membranes. Read More

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Crystal structure and functional implication of a bacterial cyclic AMP-AMP-GMP synthetase.

Nucleic Acids Res 2021 Apr 9. Epub 2021 Apr 9.

Institute of New Drug Development, China Medical University, Taichung 406, Taiwan.

Mammalian cyclic GMP-AMP synthase (cGAS) and its homologue dinucleotide cyclase in Vibrio cholerae (VcDncV) produce cyclic dinucleotides (CDNs) that participate in the defense against viral infection. Recently, scores of new cGAS/DncV-like nucleotidyltransferases (CD-NTases) were discovered, which produce various CDNs and cyclic trinucleotides (CTNs) as second messengers. Here, we present the crystal structures of EcCdnD, a CD-NTase from Enterobacter cloacae that produces cyclic AMP-AMP-GMP, in its apo-form and in complex with ATP, ADP and AMPcPP, an ATP analogue. Read More

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Metabolic fitness of is indispensable for functional drug efflux, ergosterol, and chitin biosynthesis.

Curr Med Mycol 2020 Sep;6(3):9-14

Amity Institute of Biotechnology, Amity University Haryana, Gurugram (Manesar)-122413, India.

Background And Purpose: The increment in fungal infections, particularly due to species, is alarming due to the emergence of multidrug resistance (MDR). Hence, the identification of novel drug targets to circumvent the problem of MDR requires immediate attention. The metabolic pathway, such as glyoxylate cycle (GC), which utilizes key enzymes (isocitrate lyase [ICL] and malate synthase [MLS]), enables to adapt under glucose-deficient conditions. Read More

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September 2020

Hypoxia-induced miR-27 and miR-195 regulate ATP consumption, viability, and metabolism of rat cardiomyocytes by targeting PPARγ and FASN expression.

Aging (Albany NY) 2021 Mar 26;13. Epub 2021 Mar 26.

Department of Internal Medicine, People’s Hospital of Tajik Autonomous County, Tashkurgan, Xinjiang Uygur Autonomous Region, China.

This study examined whether hypoxia-induced microRNA (miRNA) upregulation was related to the inhibition of chondriosome aliphatic acid oxidation in myocardial cells under anoxia. We showed that anoxia induced high expression of hypoxia-inducible factor-1-alpha, muscle carnitine palmitoyltransferase I, and vascular endothelial growth factor in cardiomyocytes. Meanwhile, miR-27 and miR-195 were also upregulated in hypoxia-induced cardiomyocytes. Read More

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Visualizing Lung Cellular Adaptations during Combined Ozone and LPS Induced Murine Acute Lung Injury.

J Vis Exp 2021 Mar 21(169). Epub 2021 Mar 21.

Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan;

Lungs are continually faced with direct and indirect insults in the form of sterile (particles or reactive toxins) and infectious (bacterial, viral or fungal) inflammatory conditions. An overwhelming host response may result in compromised respiration and acute lung injury, which is characterized by lung neutrophil recruitment as a result of the patho-logical host immune, coagulative and tissue remodeling response. Sensitive microscopic methods to visualize and quantify murine lung cellular adaptations, in response to low-dose (0. Read More

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Nilotinib Improves Bioenergetic Profiling in Brain Astroglia in the 3xTg Mouse Model of Alzheimer's Disease.

Aging Dis 2021 Apr 1;12(2):441-465. Epub 2021 Apr 1.

1Division of Neurodegenerative Disorders, St. Boniface Hospital Research, Winnipeg, MB, Canada.

Current treatments targeting amyloid beta in Alzheimer's disease (AD) have minimal efficacy, which results in a huge unmet medical need worldwide. Accumulating data suggest that brain mitochondrial dysfunction play a critical role in AD pathogenesis. Targeting cellular mechanisms associated with mitochondrial dysfunction in AD create a novel approach for drug development. Read More

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Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes.

Front Endocrinol (Lausanne) 2021 18;12:635175. Epub 2021 Mar 18.

Department of Medical Biology, Medical University of Bialystok, Bialystok, Poland.

Insulin resistance is defined as a complex pathological condition of abnormal cellular and metabolic response to insulin. Obesity and consumption of high-fat diet lead to ectopic accumulation of bioactive lipids in insulin-sensitive tissues. Intracellular lipid accumulation is regarded as one of the major factors in the induction of insulin resistance and type 2 diabetes (T2D). Read More

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Effects of different standard and special diets on cognition and brain mitochondrial function in mice.

Nutr Neurosci 2021 Apr 5:1-13. Epub 2021 Apr 5.

Institute of Nutritional Sciences, Laboratory for Nutrition in Prevention and Therapy, Justus-Liebig-University of Giessen, Biomedical Research Center Seltersberg (BFS), Giessen, Germany.

Human nutrition plays an important role in prevention or at least slowing down the progression of age- and diet-related diseases. Thereby, mitochondrial dysfunction represents one common underlying mechanism, which is being investigated in mouse models. However, the influence of the selected diets in preclinical studies on cognition and mitochondrial function has not yet been reported cohesively. Read More

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TRPC channel-derived calcium fluxes differentially regulate ATP and flow-induced activation of eNOS.

Nitric Oxide 2021 Apr 1. Epub 2021 Apr 1.

School of Biomedical Engineering, Science, and Health Systems, Drexel University, 3141 Market St., Philadelphia, PA 19104, USA. Electronic address:

Endothelial dysfunction, characterised by impaired nitric oxide (NO) bioavailability, arises in response to a variety of cardiovascular risk factors and precedes atherosclerosis. NO is produced by tight regulation of endothelial nitric oxide synthase (eNOS) activity in response to vasodilatory stimuli. This regulation of eNOS is mediated in part by store-operated calcium entry (SOCE). Read More

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An Integrative Proteomics and Metabolomics Analysis Reveals Metabolic Phenotype in Mice with Cardiac-specific Deletion of Natriuretic Peptide Receptor A.

Mol Cell Proteomics 2021 Mar 31:100072. Epub 2021 Mar 31.

Clinical Experimental Center, Xi'an International Medical Center Hospital, Xi'an, 710100, P.R. China. Electronic address:

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are important biological markers and cardiac function regulators. Natriuretic peptide receptor A (NPRA) binds to an ANP or BNP ligand and induces transmembrane signal transduction by elevating the intracellular cyclic guanosine monophosphate (cGMP) levels. However, the metabolic phenotype and related mechanisms induced by NPRA deletion remain ambiguous. Read More

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Mitochondria-targeted prooxidant effects of betulinic acid conjugated with delocalized lipophilic cation F16.

Free Radic Biol Med 2021 Apr 1;168:55-69. Epub 2021 Apr 1.

Mari State University, Pl. Lenina 1, Yoshkar-Ola, Mari El, 424001, Russia; Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, Pushchino, Moscow Region, 142290, Russia; Prokhorov General Physics Institute of the Russian Academy of Sciences, Vavilova 38, Moscow, 119991, Russia.

The paper examines the molecular mechanisms of the cytotoxicity of conjugates of betulinic acid with the penetrating cation F16. The in vitro experiments on rat thymocytes revealed that all the obtained F16-betulinic acid derivatives showed more than 10-fold higher cytotoxicity as compared to betulinic acid and F16. In this case, 0. Read More

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The flexibility of metabolic interactions between chloroplasts and mitochondria in Nicotiana tabacum leaf.

Plant J 2021 Apr 2. Epub 2021 Apr 2.

Department of Biological Sciences, Department of Cell and Systems Biology, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, M1C1A4, Canada.

To examine the effect of mitochondrial function on photosynthesis, wild-type and transgenic Nicotiana tabacum with varying amounts of alternative oxidase (AOX) were treated with different respiratory inhibitors. Initially, each inhibitor increased the reduction state of the chloroplast electron transport chain (cETC), most severely in AOX knockdowns and least severely in AOX overexpressors. This indicated that the mitochondrion was a necessary sink for photo-generated reductant, contributing to the "P700 oxidation capacity" of photosystem I. Read More

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Epigallocatechin-3-Gallate Plus Omega-3 Restores the Mitochondrial Complex I and FF-ATP Synthase Activities in PBMCs of Young Children with Down Syndrome: A Pilot Study of Safety and Efficacy.

Antioxidants (Basel) 2021 Mar 16;10(3). Epub 2021 Mar 16.

Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, 80131 Naples, Italy.

Down syndrome (DS) is a major genetic cause of intellectual disability. DS pathogenesis has not been fully elucidated, and no specific pharmacological therapy is available. DYRK1A overexpression, oxidative stress and mitochondrial dysfunction were described in trisomy 21. Read More

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Impaired FF-ATP-Synthase Dimerization Leads to the Induction of Cyclophilin D-Mediated Autophagy-Dependent Cell Death and Accelerated Aging.

Cells 2021 Mar 30;10(4). Epub 2021 Mar 30.

Faculty of Biosciences, Institute of Molecular Biosciences, Goethe University, 60438 Frankfurt, Germany.

Mitochondrial FF-ATP-synthase dimers play a critical role in shaping and maintenance of mitochondrial ultrastructure. Previous studies have revealed that ablation of the FF-ATP-synthase assembly factor PaATPE of the ascomycete strongly affects cristae formation, increases hydrogen peroxide levels, impairs mitochondrial function and leads to premature cell death. In the present study, we investigated the underlying mechanistic basis. Read More

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Triterpenoid Saponins Impact the Immune Recognition of Proteins in Parasitic Nematodes.

Pathogens 2021 Mar 4;10(3). Epub 2021 Mar 4.

Department of Plant Biochemistry, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland.

The influence of triterpenoid saponins on subcellular morphological changes in the cells of parasitic nematodes remains poorly understood. Our study examines the effect of oleanolic acid glucuronides from marigold () on the possible modification of immunogenic proteins from infective larvae (L3). Our findings indicate that the triterpenoid saponins alter the subcellular morphology of the larvae and prevent recognition of nematode-specific proteins by rabbit immune-IgG. Read More

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Biochemical Characterization of Recombinant UDPG-Dependent IAA Glucosyltransferase from Maize ().

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Faculty of Chemistry, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland.

Here, we report a biochemical characterization of recombinant maize indole-3-acetyl-β-d-glucose (IAGlc) synthase which glucosylates indole-3-acetic acid (IAA) and thus abolishes its auxinic activity affecting plant hormonal homeostasis. Substrate specificity analysis revealed that IAA is a preferred substrate of IAGlc synthase; however, the enzyme can also glucosylate indole-3-butyric acid and indole-3-propionic acid with the relative activity of 66% and 49.7%, respectively. Read More

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Icaritin Provides Neuroprotection in Parkinson's Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency.

Antioxidants (Basel) 2021 Mar 29;10(4). Epub 2021 Mar 29.

National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.

Neuroinflammation, oxidative stress, and mitochondrial dysfunction are all important pathogenic mechanisms underlying motor dysfunction and dopaminergic neuronal damage observed in patients with Parkinson's disease (PD). However, despite extensive efforts, targeting inflammation and oxidative stress using various approaches has not led to meaningful clinical outcomes, and mitochondrial enhancers have also failed to convincingly achieve disease-modifying effects. We tested our hypothesis that treatment approaches in PD should simultaneously reduce neuroinflammation, oxidative stress, and improve alterations in neuronal energy metabolism using the flavonoid icaritin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Read More

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Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology.

Life (Basel) 2021 Mar 15;11(3). Epub 2021 Mar 15.

Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy.

Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the FF-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. Read More

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