Analysis of molecular mechanisms of ATP synthesis from the standpoint of the principle of electrical neutrality

2017 ◽  
Vol 224 ◽  
pp. 49-58 ◽  
Author(s):  
Sunil Nath
Keyword(s):  
Molecular Mechanisms ◽  
Atp Synthesis ◽  
Electrical Neutrality

scholarly journals STIM1 Deficiency Leads to Specific Down-Regulation of ITPR3 in SH-SY5Y Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6598
Author(s):  
Carlos Pascual-Caro ◽  
Yolanda Orantos-Aguilera ◽  
Irene Sanchez-Lopez ◽  
Jaime de Juan-Sanz ◽  
Jan B. Parys ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Neuronal Cell ◽  
Atp Synthesis ◽  
Transport Systems ◽  
Synthesis Rate ◽  
Physical Interaction ◽  
Excitable Cells ◽  
Protein Levels

STIM1 is an endoplasmic reticulum (ER) protein that modulates the activity of a number of Ca2+ transport systems. By direct physical interaction with ORAI1, a plasma membrane Ca2+ channel, STIM1 activates the ICRAC current, whereas the binding with the voltage-operated Ca2+ channel CaV1.2 inhibits the current through this latter channel. In this way, STIM1 is a key regulator of Ca2+ signaling in excitable and non-excitable cells, and altered STIM1 levels have been reported to underlie several pathologies, including immunodeficiency, neurodegenerative diseases, and cancer. In both sporadic and familial Alzheimer’s disease, a decrease of STIM1 protein levels accounts for the alteration of Ca2+ handling that compromises neuronal cell viability. Using SH-SY5Y cells edited by CRISPR/Cas9 to knockout STIM1 gene expression, this work evaluated the molecular mechanisms underlying the cell death triggered by the deficiency of STIM1, demonstrating that STIM1 is a positive regulator of ITPR3 gene expression. ITPR3 (or IP3R3) is a Ca2+ channel enriched at ER-mitochondria contact sites where it provides Ca2+ for transport into the mitochondria. Thus, STIM1 deficiency leads to a strong reduction of ITPR3 transcript and ITPR3 protein levels, a consequent decrease of the mitochondria free Ca2+ concentration ([Ca2+]mit), reduction of mitochondrial oxygen consumption rate, and decrease in ATP synthesis rate. All these values were normalized by ectopic expression of ITPR3 in STIM1-KO cells, providing strong evidence for a new mode of regulation of [Ca2+]mit mediated by the STIM1-ITPR3 axis.

scholarly journals Silencing of Plasma Membrane Ca2+-ATPase Isoforms 2 and 3 Impairs Energy Metabolism in Differentiating PC12 Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Tomasz Boczek ◽  
Malwina Lisek ◽  
Bozena Ferenc ◽  
Antoni Kowalski ◽  
Magdalena Wiktorska ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Atp Synthesis ◽  
Mitochondrial Activity ◽  
Excitable Cells ◽  
Close Link ◽  
Atp Level ◽  
Atp Generation

A close link between Ca2+, ATP level, and neurogenesis is apparent; however, the molecular mechanisms of this relationship have not been completely elucidated. Transient elevations of cytosolic Ca2+may boost ATP synthesis, but ATP is also consumed by ion pumps to maintain a low Ca2+in cytosol. In differentiation process plasma membrane Ca2+ATPase (PMCA) is considered as one of the major players for Ca2+homeostasis. From four PMCA isoforms, the fastest PMCA2 and PMCA3 are expressed predominantly in excitable cells. In the present study we assessed whether PMCA isoform composition may affect energy balance in differentiating PC12 cells. We found that PMCA2-downregulated cells showed higher basal O2consumption, lower NAD(P)H level, and increased activity of ETC. These changes associated with higher[Ca2+]cresulted in elevated ATP level. Since PMCA2-reduced cells demonstrated greatest sensitivity to ETC inhibition, we suppose that the main source of energy for PMCA isoforms 1, 3, and 4 was oxidative phosphorylation. Contrary, cells with unchanged PMCA2 expression exhibited prevalence of glycolysis in ATP generation. Our results with PMCA2- or PMCA3-downregulated lines provide an evidence of a novel role of PMCA isoforms in regulation of bioenergetic pathways, and mitochondrial activity and maintenance of ATP level during PC12 cells differentiation.

Calcium, ATP, and ROS: a mitochondrial love-hate triangle

2004 ◽  
Vol 287 (4) ◽  
pp. C817-C833 ◽  
Author(s):  
Paul S. Brookes ◽  
Yisang Yoon ◽  
James L. Robotham ◽  
M. W. Anders ◽  
Shey-Shing Sheu
Keyword(s):  
Mitochondrial Dysfunction ◽  
Molecular Mechanisms ◽  
Atp Synthesis ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Oxygen Species ◽  
Negative Effects ◽  
Cytochrome C Release ◽  
Cellular Energy ◽  
Atp Generation

The mitochondrion is at the core of cellular energy metabolism, being the site of most ATP generation. Calcium is a key regulator of mitochondrial function and acts at several levels within the organelle to stimulate ATP synthesis. However, the dysregulation of mitochondrial Ca2+ homeostasis is now recognized to play a key role in several pathologies. For example, mitochondrial matrix Ca2+ overload can lead to enhanced generation of reactive oxygen species, triggering of the permeability transition pore, and cytochrome c release, leading to apoptosis. Despite progress regarding the independent roles of both Ca2+ and mitochondrial dysfunction in disease, the molecular mechanisms by which Ca2+ can elicit mitochondrial dysfunction remain elusive. This review highlights the delicate balance between the positive and negative effects of Ca2+ and the signaling events that perturb this balance. Overall, a “two-hit” hypothesis is developed, in which Ca2+ plus another pathological stimulus can bring about mitochondrial dysfunction.

Abstract 137: The Effect Of Mitophagy During Transient Ischemic Brain In Rats

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Qiang Li ◽  
Ting Zhang ◽  
Jixian Wang ◽  
Yongting Wang ◽  
Guo-Yuan Yang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Atp Synthesis ◽  
Beclin 1 ◽  
Neurological Deficits ◽  
Ischemic Brain ◽  
Pre Treatment ◽  
The Impact

Background and Purpose: Mitochondria provides energy to maintain normal cell functioning. Mitophagy is one of mitochondria functions, which can clear out injured mitochondria, ensure stability of mitochondria and promote cell survival in hostile environment. However, if mitophagy occurs during cerebral ischemia is unknown. The present study explored dynamic mitophagy, the effect of promoting mitophagy, and the molecular mechanisms of mitophagy during cerebral ischemia/reperfusion. Methods: Adult male SD rats underwent 2h middle cerebral artery occlusion (MCAO) followed by 6 to 72h reperfusion. Dynamic changes of mitophagy were determined by LC3 immunostaining, Western blot analysis, and transmission electron microscope. To study the impact of mitophagy, we injected rapamycin, a mitophagy stimulator, into the left ventricle in rats underwent transient MCAO. To evaluate the effect of mitophagy, neuronal death and neurological deficits were determined. To explore the effect of mitophagy on mitochondria function, the number of mitochondria, the levels of MDA, ATP, and JC-1 were examined. To study the mechanism of mitophagy, mitochondrial Beclin-1 and p62 expression were also determined. Results: We demonstrated that autophagy was mainly detected in mitochondria in the peri-focal area of ischemic cortex after ischemia/reperfusion. Mitophagy was increased at 6h (p<0.05), peaked at 24h (p<0.05), gradually reduced at 48h (p<0.05), and returned to normal at 72h of transient MCAO. Pre-treatment with rapamycin greatly enhanced mitophagy, reduced infarct volume, and improved neurological outcomes compared to the control (p<0.05). We found that the number of mitochondria and mtDNA copy, mitochondria ATP synthesis level, and JC-1 were increased (p<0.05), and MDA was reduced in rapamycin treated rats (p<0.05). We further demonstrated that rapamycin pre-treatment enhanced mitochondrial Beclin-1and p62 in mitochondria. Conclusion: We demonstrated ischemia could induce mitophagy in brain cells. Rapamycin attenuated ischemic brain injury, which was via stimulating mitophagy that can reduce oxidative stress and improve mitochondria function. The mechanism of rapamycin promoting mitophagy was through increasing Beclin-1 and p62 expression.

scholarly journals Research Progress in the Molecular Functions of Plant mTERF Proteins

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 205
Author(s):  
Pedro Robles ◽  
Víctor Quesada
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Transcription Termination ◽  
Atp Synthesis ◽  
Research Progress ◽  
Mitochondrial Genomes ◽  
Molecular Functions ◽  
The Many ◽  
New Research

Present-day chloroplast and mitochondrial genomes contain only a few dozen genes involved in ATP synthesis, photosynthesis, and gene expression. The proteins encoded by these genes are only a small fraction of the many hundreds of proteins that act in chloroplasts and mitochondria. Hence, the vast majority, including components of organellar gene expression (OGE) machineries, are encoded by nuclear genes, translated into the cytosol and imported to these organelles. Consequently, the expression of nuclear and organellar genomes has to be very precisely coordinated. Furthermore, OGE regulation is crucial to chloroplast and mitochondria biogenesis, and hence, to plant growth and development. Notwithstanding, the molecular mechanisms governing OGE are still poorly understood. Recent results have revealed the increasing importance of nuclear-encoded modular proteins capable of binding nucleic acids and regulating OGE. Mitochondrial transcription termination factor (mTERF) proteins are a good example of this category of OGE regulators. Plant mTERFs are located in chloroplasts and/or mitochondria, and have been characterized mainly from the isolation and analyses of Arabidopsis and maize mutants. These studies have revealed their fundamental roles in different plant development aspects and responses to abiotic stress. Fourteen mTERFs have been hitherto characterized in land plants, albeit to a different extent. These numbers are limited if we consider that 31 and 35 mTERFs have been, respectively, identified in maize and Arabidopsis. Notwithstanding, remarkable progress has been made in recent years to elucidate the molecular mechanisms by which mTERFs regulate OGE. Consequently, it has been experimentally demonstrated that plant mTERFs are required for the transcription termination of chloroplast genes (mTERF6 and mTERF8), transcriptional pausing and the stabilization of chloroplast transcripts (MDA1/mTERF5), intron splicing in chloroplasts (BSM/RUG2/mTERF4 and Zm-mTERF4) and mitochondria (mTERF15 and ZmSMK3) and very recently, also in the assembly of chloroplast ribosomes and translation (mTERF9). This review aims to provide a detailed update of current knowledge about the molecular functions of plant mTERF proteins. It principally focuses on new research that has made an outstanding contribution to unravel the molecular mechanisms by which plant mTERFs regulate the expression of chloroplast and mitochondrial genomes.

scholarly journals Ocean acidification modulates expression of genes and physiological performance of a marine diatom

2015 ◽  
Vol 12 (18) ◽  
pp. 15809-15833 ◽  
Author(s):  
Y. Li ◽  
S. Zhuang ◽  
Y. Wu ◽  
H. Ren ◽  
F. Cheng ◽  
...  
Keyword(s):  
Ocean Acidification ◽  
Molecular Mechanisms ◽  
Carbon Fixation ◽  
Atp Synthesis ◽  
High Light Intensity ◽  
Marine Diatom ◽  
Physiological Performance ◽  
Light Regimes ◽  
Expression Of Genes ◽  
Mitochondrial Atp Synthase

Abstract. Ocean Acidification (OA) is known to affect various aspects of the physiological performance of diatoms, but there is little information on the underlining molecular mechanisms involved. Here, we show that in the model diatom Phaeodactylum tricornutum expression of the genes related to light harvesting, carbon acquisition and carboxylation, nitrite assimilation and ATP synthesis are modulated by OA. Growth and photosynthetic carbon fixation were enhanced by elevated CO2 (1000 μatm) under both constant indoor and fluctuating outdoor light regimes. The genetic expression of nitrite reductase (NiR) was up-regulated by OA regardless of light levels and/or regimes. The transcriptional expression of fucoxanthin chlorophyll a/c protein (lhcf type (FCP)) and mitochondrial ATP synthase (mtATP synthase) genes were also enhanced by OA, but only under high light intensity. OA treatment decreased the expression of β-carbonic anhydrase (β-CA) along with down-regulation of CO2 concentrating mechanisms (CCMs). Additionally, the genes for these proteins (NiR, FCP, mtATP synthase, β-CA) showed diel expressions either under constant indoor light or fluctuating sunlight. Thus, OA enhanced photosynthetic and growth rates by stimulating nitrogen assimilation and indirectly by down-regulating the energy-costly inorganic carbon acquisition process.

scholarly journals Photobiomodulation Regulation as One Promising Therapeutic Approach for Myocardial Infarction

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Xinlu Gao ◽  
Wenwen Zhang ◽  
Fan Yang ◽  
Wenya Ma ◽  
Benzhi Cai
Keyword(s):  
Myocardial Infarction ◽  
Molecular Mechanisms ◽  
Contractile Function ◽  
Heart Function ◽  
Myocardial Necrosis ◽  
Atp Synthesis ◽  
Source Power ◽  
Positive Effects ◽  
Promising Therapeutic Approach ◽  
Improve Heart Function

Myocardial infarction refers to myocardial necrosis caused by acute or persistent coronary ischemia and hypoxia. It is considered to be one of the significant crises threatening human health in the world. Following myocardial infarction, collagen gradually replaces the original tissue due to the loss of many cardiomyocytes, myocardial contractile function decreases, and myocardial fibrosis eventually leads to heart failure. Phototherapy is a new treatment which has shown superior efficacy on the nerve, skeletal muscle, skin, and other tissues. Likewise, there is growing evidence that phototherapy also has many positive effects on the heart. Therefore, this article introduces the progress of research on phototherapy as a new therapeutic strategy in the treatment of myocardial infarction. The wavelength of photobiomodulation in the treatment of myocardial infarction is specific, and the influence of light source power and light duration on the tissue presents a bell-shaped distribution. Under these conditions, phototherapy can promote ATP synthesis and angiogenesis, inhibit the inflammatory response, improve heart function, reduce infarct size, and protect myocardium. In addition, we summarized the molecular mechanisms of phototherapy. According to the location of photoreceptors, they can be divided into mitochondrial and nonmitochondrial parts.

scholarly journals New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids

2021 ◽  
Author(s):  
Daniela Rodrigues ◽  
Terezinha de Souza ◽  
Luke Coyle ◽  
Matteo Di Piazza ◽  
Bram Herpers ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Cell Signalling ◽  
Mrna Translation ◽  
Atp Synthesis ◽  
Metabolome Analysis ◽  
Tissue Specific ◽  
Intestinal Toxicity

Abstract5-Fluorouracil (5-FU) is a widely used chemotherapeutical that induces acute toxicity in the small and large intestine of patients. Symptoms can be severe and lead to the interruption of cancer treatments. However, there is limited understanding of the molecular mechanisms underlying 5-FU-induced intestinal toxicity. In this study, well-established 3D organoid models of human colon and small intestine (SI) were used to characterize 5-FU transcriptomic and metabolomic responses. Clinically relevant 5-FU concentrations for in vitro testing in organoids were established using physiologically based pharmacokinetic simulation of dosing regimens recommended for cancer patients, resulting in exposures to 10, 100 and 1000 µM. After treatment, different measurements were performed: cell viability and apoptosis; image analysis of cell morphological changes; RNA sequencing; and metabolome analysis of supernatant from organoids cultures. Based on analysis of the differentially expressed genes, the most prominent molecular pathways affected by 5-FU included cell cycle, p53 signalling, mitochondrial ATP synthesis and apoptosis. Short time-series expression miner demonstrated tissue-specific mechanisms affected by 5-FU, namely biosynthesis and transport of small molecules, and mRNA translation for colon; cell signalling mediated by Rho GTPases and fork-head box transcription factors for SI. Metabolomic analysis showed that in addition to the effects on TCA cycle and oxidative stress in both organoids, tissue-specific metabolic alterations were also induced by 5-FU. Multi-omics integration identified transcription factor E2F1, a regulator of cell cycle and apoptosis, as the best key node across all samples. These results provide new insights into 5-FU toxicity mechanisms and underline the relevance of human organoid models in the safety assessment in drug development.

Mitochondrial oxidative stress mediates high-phosphate-induced secretory defects and apoptosis in insulin-secreting cells

2015 ◽  
Vol 308 (11) ◽  
pp. E933-E941 ◽  
Author(s):  
Tuyet Thi Nguyen ◽  
Xianglan Quan ◽  
Kyu-Hee Hwang ◽  
Shanhua Xu ◽  
Ranjan Das ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Stress Proteins ◽  
Mitochondrial Permeability Transition ◽  
Islet Cells ◽  
Atp Synthesis ◽  
Permeability Transition ◽  
Insulin Content ◽  
Superoxide Generation ◽  
Mitochondrial Oxidative Stress

Inorganic phosphate (P i) plays an important role in cell signaling and energy metabolism. In insulin-releasing cells, P i transport into mitochondria is essential for the generation of ATP, a signaling factor in metabolism-secretion coupling. Elevated P i concentrations, however, can have toxic effects in various cell types. The underlying molecular mechanisms are poorly understood. Here, we have investigated the effect of P i on secretory function and apoptosis in INS-1E clonal β-cells and rat pancreatic islets. Elevated extracellular P i (1∼5 mM) increased the mitochondrial membrane potential (ΔΨm), superoxide generation, caspase activation, and cell death. Depolarization of the ΔΨm abolished P i-induced superoxide generation. Butylmalonate, a nonselective blocker of mitochondrial phosphate transporters, prevented ΔΨm hyperpolarization, superoxide generation, and cytotoxicity caused by P i. High P i also promoted the opening of the mitochondrial permeability transition (PT) pore, leading to apoptosis, which was also prevented by butylmalonate. The mitochondrial antioxidants mitoTEMPO or MnTBAP prevented P i-triggered PT pore opening and cytotoxicity. Elevated extracellular P i diminished ATP synthesis, cytosolic Ca2+ oscillations, and insulin content and secretion in INS-1E cells as well as in dispersed islet cells. These parameters were restored following preincubation with mitochondrial antioxidants. This treatment also prevented high-P i-induced phosphorylation of ER stress proteins. We propose that elevated extracellular P i causes mitochondrial oxidative stress linked to mitochondrial hyperpolarization. Such stress results in reduced insulin content and defective insulin secretion and cytotoxicity. Our data explain the decreased insulin content and secretion observed under hyperphosphatemic states.

scholarly journals The transcriptional events and their relationship to physiological changes during poplar seed germination and post-germination

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Chunpu Qu ◽  
Hancheng Zhao ◽  
Jinyuan Chen ◽  
Zhuang Zuo ◽  
Xue Sun ◽  
...  
Keyword(s):  
Seed Germination ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Atp Synthesis ◽  
Enrichment Analysis ◽  
Transcriptional Level ◽  
Primary Metabolism ◽  
Expression Of Genes ◽  
Molecular Events ◽  
Acid Protein

Abstract Background Seed germination, the foundation of plant propagation, involves a series of changes at the molecular level. Poplar is a model woody plant, but the molecular events occurring during seed germination in this species are unclear. Results In this study, we investigated changes in gene transcriptional levels during different germination periods in poplar by high-throughput sequencing technology. Analysis of genes expressed at specific germination stages indicated that these genes are distributed in many metabolic pathways. Enrichment analysis of significantly differentially expressed genes based on hypergeometric testing revealed that multiple pathways, such as pathways related to glycolysis, lipid, amino acid, protein and ATP synthesis metabolism, changed significantly at the transcriptional level during seed germination. A comparison of ΣZ values uncovered a series of transcriptional changes in biological processes related to primary metabolism during poplar seed germination. Among these changes, genes related to CHO metabolism were the first to be activated, with subsequent expression of genes involved in lipid metabolism and then those associated with protein metabolism. The pattern of metabolomic and physiological index changes further verified the sequence of some biological events. Conclusions Our study revealed molecular events occurring at the transcriptional level during seed germination and determined their order. These events were further verified by patterns of changes of metabolites and physiological indexes. Our findings lay a foundation for the elucidation of the molecular mechanisms responsible for poplar seed germination.

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