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ATP synthesis

Jianshu Dong, Fahui Li, Feng Gao, Jia Wei, Yajing Lin, Yong Zhang, Jizhong Lou, Guangfeng Liu, Yuhui Dong, Lin Liu, Hongmin Liu, Jiangyun Wang, Weimin Gong
The accurate modification of the tRNAIle anticodon wobble cytosine 34 is critical for AUA decoding in protein synthesis. Archaeal tRNAIle2 cytosine 34 is modified with agmatine in the presence of ATP by TiaS (tRNAIle2 agmatidine synthetase). Yet, no structure of apo-form full length TiaS is available currently. Here, the crystal structures of apo TiaS and a complex of TiaS-agmatine-AMPPCP-Mg are presented, with properly folded zinc ribbon and Cys4-zinc coordination identified. Compared with tRNAIle2 bound form, the architecture of apo TiaS shows a totally different conformation of zinc ribbon...
August 16, 2018: Journal of Molecular Biology
Xiaolong Zhu, Juan Cai, Fan Zhou, Zulin Wu, Dan Li, Youbin Li, Zhiping Xie, Yiting Zhou, Yongheng Liang
Honokiol (HNK), an important medicinal component of Magnolia officinalis, is reported to possess pharmacological activities against a variety of diseases. However, the molecular mechanisms of HNK medicinal functions are not fully clear. To systematically study the mechanisms of HNK action, we screened a yeast mutant library based on the conserved nature of its genes among eukaryotes. We identified genes associated with increased resistance or sensitivity to HNK after mutation. After functional classification of these genes, we found that most HNK-resistant strains in the largest functional category were petites with mutations in mitochondrial genes, indicating that mitochondria were related to HNK resistance...
August 17, 2018: Traffic
Alexei A Stuchebrukhov
In aerobic cells, the proton gradient that drives ATP synthesis is created by three different proton pumps-membrane enzymes of the respiratory electron transport chain known as complex I, III, and IV. Despite the striking dissimilarity of structures and apparent differences in molecular mechanisms of proton pumping, all three enzymes have much in common and employ the same universal physical principles of converting redox energy to proton pumping. In this study, we describe a simple mathematical model that illustrates the general principles of redox-driven proton pumps and discuss their implementation in complex I, III, and IV of the respiratory chain...
August 2, 2018: Biophysical Journal
Pascal Albanese, Marcello Manfredi, Angela Re, Emilio Marengo, Guido Saracco, Cristina Pagliano
Plant thylakoid membranes contain hundreds of proteins closely interplaying to cope with ever-changing environmental conditions. We investigated how Pisum sativum L. (pea) grown at different irradiances optimizes light-use efficiency through the differential accumulation of thylakoid proteins. Thylakoid membranes from plants grown under low (LL), moderate (ML) and high (HL) light intensity were characterized by combining chlorophyll fluorescence measurements with quantitative label-free proteomic analysis. Protein sequences retrieved from available transcriptomic data considerably improved the thylakoid proteome profiling, increasing the quantifiable proteins from 63 to 194...
August 17, 2018: Plant Journal: for Cell and Molecular Biology
Xiao Yu Tian, Shuangtao Ma, Gary Tse, Wing Tak Wong, Yu Huang
Uncoupling protein 2 (UCP2) belongs to the family of mitochondrial anion carrier proteins. It uncouples oxygen consumption from ATP synthesis. UCP2 is ubiquitously expressed in most cell types to reduce oxidative stress. It is tightly regulated at the transcriptional, translational, and post-translational levels. UCP2 in the cardiovascular system is being increasingly recognized as an important molecule to defend against various stress signals such as oxidative stress in the pathology of vascular dysfunction, atherosclerosis, hypertension, and cardiac injuries...
2018: Frontiers in Physiology
Jin Yu, Hong Zhu, Saeid Taheri, Stephen Perry, Mark S Kindy
The consumption of fruits and vegetables appears to help with maintaining an adequate level of exercise and improves endurance. However, the mechanisms that are involved in this process are not well understood. In the current study, the impact of diets enriched in fruits and vegetables (GrandFusion® ) on exercise endurance was examined in a mouse model. GrandFusion (GF) diets increased mitochondrial DNA and enzyme activity, while they also stimulated mitochondrial mRNA synthesis in vivo. GF diets increased both the mRNA expression of factors involved in mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (Tfam), estrogen-related receptor alpha (ERRα), nuclear respiratory factor 1 (NRF-1), cytochrome c oxidase IV (COXIV) and ATP synthase (ATPsyn)...
August 16, 2018: Nutrients
Myungseo Park, Daesil Nam, Dae-Hyuk Kweon, Dongwoo Shin
RpoS is one of several alternative sigma factors known to alter gene expression profiles by RpoS-associated RNA polymerase in response to a variety of stresses. The enteric bacteria Salmonella enterica and Escherichia coli accumulate RpoS under low Mg2+ concentrations via a common mechanism in which the PhoP regulator activates expression of antiadaptor proteins that, by sequestering the adaptor RssB, prevent RpoS degradation by the protease ClpXP. Here, we demonstrate that this genetic program alone does not fully support RpoS accumulation when cytoplasmic Mg2+ concentration drops to levels that impair protein synthesis...
August 15, 2018: Molecular Microbiology
Chandrakant Bagul, Garikapati Koteswara Rao, Venkata Krishna Kanth Makani, Jaki R Tamboli, Manika Pal-Bhadra, Ahmed Kamal
A series of pyrazolo[1,5- a ]pyrimidines substituted at C5 with 1-phenylprop-2-en-1-one ( 6a-q ) and 3-phenylprop-2-en-1-one ( 7a-k ) was synthesized and evaluated for antiproliferative activity. Among them, 6h was found to be the most active compound against the MDA-MB-231 cell line with an IC50 of 2.6 μM . The antiproliferative activity of this series of compounds ranged from 2.6 to 34.9 μM against A549 (lung cancer), MDA-MB-231 (breast cancer) and DU-145 (prostate cancer) cell lines. FACS analysis revealed that these hybrids arrest the cell cycle at the subG1 phase...
September 1, 2017: MedChemComm
D Maciejewska, J Żabiński, M Rezler, P Kaźmierczak, M S Collins, L Ficker, M T Cushion
Here we describe the potency of 21 pentamidine analogues against the fungal pathogen, Pneumocystis carinii , in an ATP bioluminescent assay with toxicity profiles in 2 mammalian cell lines. Reduction of two 5-methyl-1,2,4-oxadiazole rings was applied to the synthesis of acid-labile bisamidines. Anti- Pneumocystis activity is discussed in the context of 3 groups of compounds depending on the main structural changes of the pentamidine lead structure. The groups include: 1) 1,4-bis(methylene)piperazine derivatives 1-5 ; 2) alkanediamide derivatives 6-10 ; 3) alkane-derived bisbenzamidines 11-21 ...
October 1, 2017: MedChemComm
Joe E Springer, Pareshkumar Prajapati, Patrick G Sullivan
The mitochondrion serves many functions in the central nervous system (CNS) and other organs beyond the well-recognized role of adenosine triphosphate (ATP) production. This includes calcium-dependent cell signaling, regulation of gene expression, synthesis and release of cytotoxic reactive oxygen species, and the release of cytochrome c and other apoptotic cell death factors. Traumatic injury to the CNS results in a rapid and, in some cases, sustained loss of mitochondrial function. One consequence of compromised mitochondrial function is induction of the mitochondrial permeability transition (mPT) state due to formation of the cyclosporine A sensitive permeability transition pore (mPTP)...
August 2018: Neural Regeneration Research
Jianmei Gao, Shuang Liu, Fan Xu, Yuangui Liu, Chun Lv, Yan Deng, Jingshan Shi, Qihai Gong
Oxidative stress-induced neuronal cell damage is a crucial factor in the pathogenesis of mitochondria-associated neurological diseases. Therefore, elimination of overproduction of mitochondrial reactive oxygen species (mtROS) may be a potential strategy for prevention and treatment of neurological diseases. In the present study, the neuroprotective effects of trilobatin (TLB), a novel small molecule monomer derived from Lithocarpus polystachyus Rehd, and its underlying mechanisms were investigated in vitro using hydrogen peroxide (H2 O2 )-induced oxidative stress model in a neuron-like PC12 cell...
2018: Frontiers in Molecular Neuroscience
Yogi Umbarawan, Mas Rizky A A Syamsunarno, Norimichi Koitabashi, Hideru Obinata, Aiko Yamaguchi, Hirofumi Hanaoka, Takako Hishiki, Noriyo Hayakawa, Motoaki Sano, Hiroaki Sunaga, Hiroki Matsui, Yoshito Tsushima, Makoto Suematsu, Masahiko Kurabayashi, Tatsuya Iso
The energy metabolism of the failing heart is characterized by reduced fatty acid (FA) oxidation and an increase in glucose utilization. However, little is known about how energy metabolism-function relationship is relevant to pathophysiology of heart failure. Recent study showed that the genetic deletion of CD36 (CD36KO), which causes reduction in FA use with an increased reliance on glucose, accelerates the progression from compensated hypertrophy to heart failure. Here, we show the mechanisms by which CD36 deletion accelerates heart failure in response to pressure overload...
August 13, 2018: Scientific Reports
Xiliang Du, Taiyu Shen, Heyuan Wang, Xia Qin, Dongmei Xing, Qianqian Ye, Zhen Shi, Zhiyuan Fang, Yiwei Zhu, Yuchen Yang, Zhicheng Peng, Chenxu Zhao, Bin Lv, Xiaobing Li, Guowen Liu, Xinwei Li
The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. Fatty liver is one of the main health disorders after parturition. Therefore, to investigate changes in hepatic lipid metabolic status and mitochondria in dairy cows with mild fatty liver, liver and blood samples were collected from healthy cows (n = 15) and cows with mild fatty liver (n = 15). To determine the effects of palmitic acids (PA), one of the major component of fatty acids, on lipid metabolism and mitochondria in vitro, calf hepatocytes were isolated from healthy calves and treated with various concentrations of PA (0, 50, 100, and 200 μM)...
August 9, 2018: Journal of Dairy Science
Marisha Sharma, Sunil K Gupta, Baisakhi Majumder, Vivek K Maurya, Farah Deeba, Afroz Alam, Vivek Pandey
Drought is a major concern for sustainable yield under changing environment. Soybean, an economically important oil and protein crop, is prone to drought resulting in yield instability. Salicylic acid (SA), a multifaceted growth hormone, modulates a series of parallel processes to confer drought tolerance thereby relieving yield limitations. The present study was performed in soybean plants treated with SA (0.5 mM) through seed pretreatment under drought regimes: severe stress (50% RWC) and moderate stress (75% RWC), and rehydration...
August 6, 2018: Plant Physiology and Biochemistry: PPB
Ahmed Elkamhawy, Jung-Eun Park, Ahmed H E Hassan, Ae Nim Pae, Jiyoun Lee, Sora Paik, Beoung-Geon Park, Eun Joo Roh
Herein, we report synthesis and evaluation of new twenty-eight pyrazinyl ureas against β amyloid (Aβ)-induced opening of mitochondrial permeability transition pore (mPTP) using JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The neuroprotective effect of seventeen compounds against Aβ-induced mPTP opening was superior to that of the standard Cyclosporin A (CsA). Among them, 1-(3-(benzyloxy)pyrazin-2-yl)-3-(3,4-dichlorophenyl)urea (5) effectively maintained mitochondrial function and cell viabilities on ATP assay and MTT assay...
July 31, 2018: European Journal of Medicinal Chemistry
Sampada Kallol, Xiao Huang, Stefan Müller, Corneille Edgar Ontsouka, Christiane Albrecht
Cholesterol is indispensable for cellular membrane composition and function. It is also a precursor for the synthesis of steroid hormones, which promote, among others, the maturation of fetal organs. A role of the ATP-binding-cassette-transporter-A1 (ABCA1) in the transport of maternal cholesterol to the fetus was suggested by transferring cholesterol to apolipoprotein-A-1 (apo-A1), but the directionality of the apoA-1/ABCA1-dependent cholesterol transport remains unclear. We isolated primary trophoblasts from term placentae to test the hypotheses that (1) apoA-1/ABCA1 dispatches cholesterol mainly towards the fetus to support fetal developmental maturation at term, and (2) differentiated syncytiotrophoblasts (STB) exert higher cholesterol transport activity than undifferentiated cytotrophoblasts (CTB)...
August 9, 2018: International Journal of Molecular Sciences
Domenica Lovero, Luca Giordano, René Massimiliano Marsano, Alvaro Sanchez-Martinez, Hadi Boukhatmi, Maik Drechsler, Marta Oliva, Alexander J Whitworth, Damiano Porcelli, Corrado Caggese
Mitochondrial disorders associated with genetic defects of the ATP synthase are among the most deleterious diseases of the neuromuscular system that primarily manifest in newborns. Nevertheless, the number of established animal models for the elucidation of the molecular mechanisms behind such pathologies is limited. In this paper, we target the Drosophila melanogaster gene encoding for the ATP synthase subunit c, ATPsynC, in order to create a fruit fly model for investigating defects in mitochondrial bioenergetics and to better understand the comprehensive pathological spectrum associated with mitochondrial ATP synthase dysfunctions...
2018: PloS One
Prassanna Rao, Tania A Rozgaja, Abdulaziz Alqahtani, Julia E Grimwade, Alan C Leonard
Although the mechanisms that precisely time initiation of chromosome replication in bacteria remain unclear, most clock models are based on accumulation of the active initiator protein, DnaA-ATP. During each cell division cycle, sufficient DnaA-ATP must become available to interact with a distinct set of low affinity recognition sites in the unique chromosomal replication origin, oriC , and assemble the pre-replicative complex (orisome) that unwinds origin DNA and helps load the replicative helicase. The low affinity oriC -DnaA-ATP interactions are required for the orisome's mechanical functions, and may also play a role in timing of new rounds of DNA synthesis...
2018: Frontiers in Microbiology
Alice P Sowton, Sarah L Millington-Burgess, Andrew J Murray, Matthew T Harper
Platelet activation plays a key role in normal haemostasis and pathological thrombosis. Platelet activation is rapid; within minutes of stimulation, platelets generate bioactive phospholipids, secrete their granule contents, activate integrins and aggregate together to form a haemostatic plug. These events are dependent on ATP synthesis. Mitochondrial function in platelets from healthy volunteers and patients with a range of diseases indicate an important role for oxygen consumption in oxidative phosphorylation in normal and pathological function...
August 6, 2018: Biochemical and Biophysical Research Communications
Samia Neggazi, Laurence Canaple, Nadjiba Hamlat, Karine Gauthier, Jacques Samarut, Giampiero Bricca, Souhila Aouichat-Bouguerra, Michel Beylot
Thyroid hormone (TH) regulates gene transcription by binding to TH receptors (TRs). TRs regulate the genes of lipid metabolism and the renin-angiotensin system (RAS). We examined the effect of TRα deletion in ApoE-/- mice (DKO mice) on the following: (i) the expression of genes controlling cholesterol metabolism and tissue (t)RAS in the liver and aorta and (ii) the expression of these genes and the regulation of cholesterol content in cultured vascular smooth muscle cells (VSMCs). TRα deletion in ApoE-/- mice led to the repression of genes involved in the synthesis and influx of cholesterol in the liver...
August 9, 2018: Journal of Vascular Research
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