Process Of Oxidative Phosphorylation Research Articles

Effect of cold atmospheric plasma (CAP) on the energy metabolism in HeLa cells through miRNA regulation

Abstract Cold atmospheric plasma (CAP) is an emerging tool for tumor treatment because it can inhibit cancer cell proliferation primarily through oxidative stress due to CAP-induced reactive oxygen species (ROS). Among various ROS targeting molecules in the cancer cells, miRNAs are one kind of important targets that can be stimulated by ROS, and many studies have shown that miRNAs are involved in the metabolism regulation of cancer cells. In this study, we applied helium-CAP (He-CAP) to HeLa cells, and observed that the ROS induced by He-CAP could modulate the miRNAs related to energy metabolism, leading to the changes of proliferation, glycolysis, TCA cycling and oxidative phosphorylation in the HeLa cells, and affected the related HIF-1, p53, PI3K/AKT signaling pathways. In addition, the analysis of miRNAs in the metabolic network revealed that the expressions of the miRNAs responsible for the promotion of energy metabolism increased, and correspondingly, the involved mRNA and protein expression decreased. As such, this study has not only demonstrated that CAP treatment could significantly change the miRNAs expression of cancer cells, but also provided a more in-depth understanding of the CAP effects on glycolysis, TCA cycling and oxidative phosphorylation processes in the cells through the comprehensive analysis of the miRNAs regulation.

Sterilization mechanism of CuCeOx on fungus: Oxidative damage and energy metabolism disequilibrium

Pathogens in bioaerosols and aquatic environment cause epidemic outbreak frequently. Relative to bacteria and virus, fungi has not received attention enough. The development of sterilization materials and mechanism on fungi are limited. In this study, we proposed a non-noble metal sterilization material CuCeOx in order to investigate its sterilization mechanism on target fungal Hanseniaspora uvarum collected from the air. The active components of CuCeOx were uniformly distributed and induced the production of R·. The reactive oxygen species (ROS) changed from R· to RO· upon contact with fungal cells. Transcriptomics identified 1665 Differentially Expressed Genes (DEGs), including 1540 up-regulated and 125 down-regulated genes. The cell wall and external encapsulation structure were firstly damaged when the fungus contacted with CuCeOx, and the related DEGs were significantly down-regulated. CuCeOx could exert great impact on the energy metabolism of the cell, especially on the process of oxidative phosphorylation, which contained 59 up-regulated and 2 down-regulated genes. The cell is not sufficient to cope with the adverse environment caused by oxidative stress and metal ion homeostatic imbalance, which then modulates the intrinsic apoptotic pathway triggering apoptosis.

Biochemical and Transcriptomic Analyses Reveal Key Salinity and Alkalinity Stress Response and Tolerance Pathways in Salix linearistipularis Inoculated with Trichoderma

Soil salinization and alkalinization are pervasive environmental issues that severely restrict plant growth and crop yield. Utilizing plant growth-promoting rhizobacteria (PGPR) is an effective strategy to enhance plant tolerance to saline–alkaline stress, though the regulatory mechanisms remain unclear. This study employed biochemical and RNA-Seq methods to uncover the critical growth-promoting effects of Trichoderma spp. on Salix linearistipularis under saline–alkaline stress. The results showed that, during saline–alkaline stress, inoculation with Trichoderma sp. M4 and M5 significantly increased the proline and soluble sugar contents in Salix linearistipularis, enhanced the activities of SOD, POD, CAT, and APX, and reduced lipid peroxidation levels, with M4 exhibiting more pronounced effects than M5. RNA-Seq analysis of revealed that 11,051 genes were upregulated after Trichoderma sp. M4 inoculation under stress conditions, with 3532 genes primarily involved in carbon metabolism, amino acid biosynthesis, and oxidative phosphorylation—processes that alleviate saline–alkaline stress. Additionally, 7519 genes were uniquely upregulated by M4 under stress, mainly enriched in secondary metabolite biosynthesis, amino acid metabolism, cyanamide metabolism, and phenylpropanoid biosynthesis. M4 mitigates saline–alkaline stress-induced damage in Salix linearistipularis seedlings by reducing oxidative damage, enhancing organic acid and amino acid metabolism, and activating phenylpropanoid biosynthesis pathways to eliminate harmful ROS. This enhances the seedlings’ tolerance to saline–alkaline stress, providing a basis for studying fungi–plant interactions under such conditions.

Combination of transcriptomics and proteomics for analyzing potential biomarker and molecular mechanism underlying skeletal muscle atrophy.

The skeletal muscle atrophy is prevalently occurred in numerous chronic disease complications. Despite its important clinical significance, there are currently no therapeutic drugs, so new biomarkers and molecular mechanisms need to be discovered urgently. Transcriptome and proteome sequencing data were collected from normal and skeletal muscle atrophic mice. The differentially expressed genes (DEGs) and proteins (DEPs) were analyzed. Applying PPI analysis to obtain overlapping genes and proteins, which were next subjected to GO and KEGG enrichment analysis. Combined analysis of transcriptomics and proteomics was performed to get key genes that were simultaneously found in GO and KEGG enrichment results. Subsequently, RT-qPCR and immunofluorescence were constructed to verify the expression of screened key genes. By combination of transcriptomics, proteomics analysis and RT-qPCR results, we identified 14 key genes (Cav1, Col3a1, Dnaja1, Postn, Ptges3, Cd44, Clec3b, Igfbp6, Lamc1, Alb, Itga6, Mmp2, Timp2 and Cd9) that were markedly different in atrophic mice. Single-gene GSEA and immunofluorescence suggested Cd9 was probably the biomarker for skeletal muscle atrophy. Our study hinted that Cd9 was potential biomarker and may interfere with skeletal muscle atrophy through process of aerobic respiration, oxidative phosphorylation, and metabolism of amino acids and fatty acids. The present study holds the subsequent significance: Frist, we investigated biomarkers for skeletal muscle atrophy using multi-omics approach. A total of 14 genes were markedly different in skeletal muscle atrophic mice. We finally found Cd9 is a potential biomarker for skeletal muscle atrophy. Our work presents novel biomarkers and potential regulatory mechanisms for the early detection and intervention of muscle atrophy.

Antifungal Activity and Mechanism of Diaporthein B against Botryosphaeria dothidea in Prevention of Apple Ring Rot.

Apple ring rot, caused by the pathogenic fungus Botryosphaeria dothidea, has inflicted substantial economic losses and caused significant food safety concerns. In this study, a pimarane-type diterpenoid, diaporthein B (DTB), isolated from a marine-derived fungus, exhibited significant antifungal activity against B. dothidea, with an EC50 value of 8.8 μg/mL. Transcriptome, metabolome, and physiological assays revealed that DTB may target mitochondria and disrupt the tricarboxylic acid (TCA) cycle and oxidative phosphorylation processes. This interference led to increased accumulation of reactive oxygen species and subsequent lipid peroxidation, ultimately inhibiting fungal growth. Furthermore, DTB exhibited an inhibitory potency against apple ring rot at a concentration of 31.2 μg/mL, achieving rates ranging from 67.7 to 81.6% across four distinct apple cultivars. These results indicated that DTB could serve as a novel fungicide for controlling apple ring rot in apple cultivation, transportation, and storage.

Benign and conserved DNA variants m.8860A>G and m.8701A>G indicating mitochondrial genetic drift in Pakistani population

BackgroundMitochondria are vital subcellular organelles that orchestrate the intricate process of oxidative phosphorylation (OXPHOS), generating adenosine triphosphate (ATP) as the primary energy molecule fueling cellular activities. During our research on mitochondrial mutations in breast cancer patients, we identified two notable single nucleotide polymorphisms (SNPs) present in both cancer patients and control individuals from the Pakistani population. Materials and methodsDNA was extracted from the blood samples of 30 individuals, and MT-ATP8 and MT-ATP6 were amplified using PCR with specific primers. Purified PCR products were sequenced and analyzed for mutations using SnapGene and BioEdit. Bioinformatics tools, Consurf and PolyPhen-2, were used to analyze the genetic variants and their impact on protein function and stability. ResultsThe analysis revealed two significant mutations in MT-ATP6 gene i.e., m.8860A>G (found in all 30 out of 30 samples) which results in the variant p.(Thr112Ala) and m.8701A>G (found in 13 out of 30 samples) which results in the variant p.(Thr59Ala). PolyPhen-2 analysis reveals the benign nature of both mutations, suggesting that the sequence variants are unlikely to cause any adverse effects on protein structure and function.

Effects of Agro-based Adsorbents on the Biochemical Profiles of Wistar Rats Exposed to Cyanide

Background: Cyanide is a very toxic chemical that reacts with the ferric cytochrome oxidase in the mitochondrial system to form a stable complex. This complex inhibits the process of oxidative phosphorylation, thereby interrupting aerobic respiration in the organism. It is postulated that activated charcoal (AC) intercepts the ingested cyanide in the gastrointestinal tract before it is absorbed into the system. Methods: A single dose of 3 mg/kg body weight of potassium cyanide (KCN) was orally administered to the rats in each of the five groups, each consisting of 6 rats. After 15 minutes, all rats in each group were given AC from different agro-based materials. The control group (group 1) received standard commercial AC orally at 1 g/kg. group 2 received AC from plantain peels, group 3 received AC from castor oil seed shell, group 4 received AC from coconut shell and group 5 received a combination of AC from plantain peels, castor oil seed shell, and coconut shell. Blood samples were collected sequentially from rats in each group for biochemical assays using standard procedures. Results: The control group, which received KCN and standard commercial AC, exhibited the highest alanine transaminase (ALT) value (60.09±0.10 U/L) on day seven. Similarly, the highest aspartate transaminase (AST) value (196.28±0.72 U/L) was observed in the control group. Alkaline phosphate (ALP) levels followed a similar pattern. On day seven, the serum creatinine levels were 3.81±0.11 mg/dL for group 1 and 3.45±0.05 mg/dL for group 5. Subsequently, all biochemical parameters decreased after day 7, with the lowest levels recorded in rats that received AC derived from coconut shells. Conclusion: The administration of locally prepared agro-based adsorbents to Wistar rats after exposure to sublethal doses of cyanide significantly mitigated the effects of the cyanide on the liver, kidneys, and heart, as indicated by the biochemical parameters of the albino Wistar rats in the study.

Integrated analysis of omics reveals the role of scapular fat in thermogenesis adaptation in sunite sheep

Inhabiting some of the world's most inhospitable climatic regions, the Sunite Mongolian sheep generates average temperatures as low as 4.3 °C and a minimum temperature of −38.8 °C; in these environments, they make essential cold adaptations. In this regard, scapular fat tissues from Mongolian sheep were collected both in winter and summer for transcriptomic and proteomic analyses to identify genes related to adaptive thermogenesis. In the transcriptome analysis, 588 differentially expressed genes were identified to participate in smooth muscle activity and fat metabolism, as well as in nutrient regulation. There were 343 upregulated and 245 downregulated genes. GO and KEGG pathway analyses on these genes revealed their participation in regulating smooth muscle activity, metabolism of fats, and nutrients. Proteomic analysis showed the differential expression of 925 proteins: among them, there are 432 up- and 493 down-expressed proteins. These proteins are mainly involved in oxidative phosphorylation, respiratory chain complex assembly, and ATP production by electron transport. Furthermore, using both sets at a more detailed level of analysis revealed over-representation in gene ontology categories related to hormone signaling, metabolism of lipids, the pentose phosphate pathway, the TCA cycle, and especially the process of oxidative phosphorylation. The identified essential genes and proteins were further validated by quantitative real-time polymerase chain reaction and Western blotting, respectively; key metabolic network constriction was constructed. The present study emphasized the critical role of lipid turnover in scapular fat for thermogenic adaptation in Sunite sheep.

Effect of Coenzyme Q10 on early wound healing after recession coverage surgery with the modified coronally advanced tunnel technique and a connective tissue graft: A 6-month, triple-blinded, randomized, placebo-controlled pilot trial

ObjectivesCoenzyme Q10 (CoQ10) or ubiquinone is one of a cell’s most important electron carriers during oxidative phosphorylation and many other cellular processes. As a strong anti-oxidant with further anti-inflammatory effects CoQ10 is of potential therapeutical value. The aim of this randomized controlled clinical trial was to investigate the effect of topical CoQ10 on early wound healing after recession coverage surgery using the modified coronally advanced tunnel (MCAT) and palatal connective tissue graft (CTG).Materials and methodsThirty patients with buccal gingival recessions were evaluated after being randomly allocated to: 1) MCAT and CTG with topical application of a coenzyme Q10 spray for 21 days or 2) MCAT and CTG with placebo spray. Wound healing was evaluated by the early wound healing index (EHI). Patient-reported pain was analyzed by a 100-mm visual analogue scale (VAS) at day 2, 7, 14 and 21 post-surgically. Mean recession coverage, gain of keratinized tissue and esthetic outcomes were assessed at 6 months.ResultsEHI and pain scores showed no significant differences. Time to recovery defined as VAS<10 mm was shorter in the test group. Mean root coverage after 6 months was 84.62 ± 26.57% and 72.19 ± 26.30% for test and placebo, p=0.052. Complete root coverage was obtained in 9 (60%) test and in 2 (13.3%) placebo patients. Increase in keratinized tissue width and esthetical outcomes were similar for both groups.ConclusionCoQ10 had no significant effect on early wound healing and on mean root coverage after 6 months.Clinical relevanceEarly wound healing: in young healthy patients with no inflammatory oral conditions topical CoQ10 does not improve early healing.

Altered Inflammatory State and Mitochondrial Function Identified by Transcriptomics in Paediatric Congenital Heart Patients Prior to Surgical Repair.

Congenital heart disease (CHD) remains the most common birth defect, with surgical intervention required in complex cases. Right ventricle (RV) function is known to be a major predictor of sustained cardiac health in these patients; thus, by elucidating the divergent profiles between CHD and the control through tissue analysis, this study aims to identify new avenues of investigation into the mechanisms surrounding reduced RV function. Transcriptomic profiling, in-silico deconvolution and functional network analysis were conducted on RV biopsies, identifying an increase in the mitochondrial dysfunction genes RPPH1 and RMPR (padj = 4.67 × 10-132, 2.23 × 10-107), the cytotoxic T-cell markers CD8a, LAGE3 and CD49a (p = 0.0006, p < 0.0001, and p = 0.0118) and proinflammatory caspase-1 (p = 0.0055) in CHD. Gene-set enrichment identified mitochondrial dysfunctional pathways, predominately changes within oxidative phosphorylation processes. The negative regulation of mitochondrial functions and metabolism was identified in the network analysis, with dysregulation of the mitochondrial complex formation. A histological analysis confirmed an increase in cellular bodies in the CHD RV tissue and positive staining for both CD45 and CD8, which was absent in the control. The deconvolution of bulk RNAseq data suggests a reduction in CD4+ T cells (p = 0.0067) and an increase in CD8+ T cells (p = 0.0223). The network analysis identified positive regulation of the immune system and cytokine signalling clusters in the inflammation functional network, as there were lymphocyte activation and leukocyte differentiation. Utilising RV tissue from paediatric patients undergoing CHD cardiac surgery, this study identifies dysfunctional mitochondrial pathways and an increase in inflammatory T-cell presence prior to reparative surgery.

Quantitative phosphoproteomics reveals molecular pathway network in wheat resistance to stripe rust

Protein phosphorylation plays an important role in immune signaling transduction in plant resistance to pathogens. Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), severely devastates wheat production. Nonetheless, the molecular mechanism of wheat resistance to stripe rust remains limited. In this study, quantitative phosphoproteomics was employed to investigate the protein phosphorylation changes in wheat challenged by Pst. A total of 1537 and 2470 differentially accumulated phosphoproteins (DAPs) were identified from four early infection stage (6, 12, 18 and 24 h post-inoculation) in incompatible and compatible wheat-Pst interactions respectively. KEGG analysis revealed that Oxidative Phosphorylation, Phosphatidylinositol Signaling, and MAPK signaling processes are distinctively enriched in incompatible interaction, while Biosynthesis of secondary metabolites and RNA degradation process were significantly enriched in compatible interactions. In particular, abundant changes in phosphorylation levels of chloroplast proteins were identified, suggesting the regulatory role of photosynthesis in wheat-Pst interaction, which is further emphasized by protein-protein interaction (PPI) network analysis. Motif-x analysis identified [xxxxSPxxxx] motif, likely phosphorylation sites for defensive response-related kinases, and a new [xxxxSSxxxx] motif significantly enriched in incompatible interaction. The results shed light on the early phosphorylation events contributing to wheat resistance against Pst. Moreover, our study demonstrated that the phosphorylation levels of Nucleoside diphosphate kinase TaNAPK1 are upregulated at 12 hpi with CYR23 and at 24 hpi with CYR31. Transient silencing of TaNAPK1 was able to attenuate wheat resistance to CYR23 and CYR31. Our study provides new insights into the mechanisms underlying Pst-wheat interactions and may provide database to find potential targets for the development of new resistant varieties.

Nicotinamide Mononucleotide in the Context of Myocardiocyte Longevity.

Cellular and subcellular metabolic activities are crucial processes involved in the regulation of intracellular homeostasis, including cellular and subcellular signaling pathways. Dysregulation of intracellular regulation mechanisms is catastrophic and cumulates into cell death. To overcome the issue of dysregulation of intracellular regulation mechanisms, the preservation of subcellular and extracellular components is essential to maintain healthy cells with increased longevity. Several physiopathological changes occur during cell ageing, one of which is the dysregulation of intracellular physiology of the oxidative phosphorylation process. Nicotinamide mononucleotide (NMN) remains in the debut of anti-aging therapeutic effect. Aged myocardiocyte characterized by disrupted NMN and or its precursors or signaling pathways. Simultaneously, several other pathophysiological occur that collectively impair intracellular homeostasis. The NMN role in the antiaging effect remains unclear and several hypotheses have been introduced into describing the mechanism and the potential outcomes from NMN exogenous supply. Correction of the impaired intracellular homeostasis includes correction to the NMN metabolism. Additionally, autophagy correction, which is the key element in the regulation of intracellular intoxication, including oxidative stress, unfolding protein response, and other degradation of intracellular metabolites. Several signaling pathways are involved in the regulation mechanism of NMN effects on myocardiocyte health and further longevity. NMN protects myocardiocytes from ischemic injury by reducing anabolism and, increasing catabolism and further passing the myocardiocytes into dormant status. NMN applications include ischemic heart, disease, and failed heart, as well as dilated cardiomyopathies. Cytosolic and mitochondrial NADPH are independently functioning and regulating. Each of these plays a role in the determination of the longevity of the myocardiocytes. NMN has a cornerstone in the functionality of Sirtuins, which are an essential anti-senescent intrinsic molecule. The study aims to assess the role of NMN in the longevity and antisenescent of myocardiocytes.

Integrated multi-omic analyses uncover the effects of aging on cell-type regulation in glucose-responsive tissues.

Aging significantly influences cellular activity and metabolism in glucose-responsive tissues, yet a comprehensive evaluation of the impacts of aging and associated cell-type responses has been lacking. This study integrates transcriptomic, methylomic, single-cell RNA sequencing, and metabolomic data to investigate aging-related regulations in adipose and muscle tissues. Through coexpression network analysis of the adipose tissue, we identified aging-associated network modules specific to certain cell types, including adipocytes and immune cells. Aging upregulates the metabolic functions of lysosomes and downregulates the branched-chain amino acids (BCAAs) degradation pathway. Additionally, aging-associated changes in cell proportions, methylation profiles, and single-cell expressions were observed in the adipose. In the muscle tissue, aging was found to repress the metabolic processes of glycolysis and oxidative phosphorylation, along with reduced gene activity of fast-twitch type II muscle fibers. Metabolomic profiling linked aging-related alterations in plasma metabolites to gene expression in glucose-responsive tissues, particularly in tRNA modifications, BCAA metabolism, and sex hormone signaling. Together, our multi-omic analyses provide a comprehensive understanding of the impacts of aging on glucose-responsive tissues and identify potential plasma biomarkers for these effects.

The Pathogenic Mechanism of Enterocytozoon hepatopenaei in Litopenaeus vannamei.

Enterocytozoon hepatopenaei (EHP) is a parasite in shrimp farming. EHP mainly parasitizes the hepatopancreas of shrimp, causing slow growth, which severely restricts the economic income of shrimp farmers. To explore the pathogenic mechanism of EHP, the host subcellular construction, molecular biological characteristics, and mitochondrial condition of Litopenaeus vannamei were identified using transmission electron microscopy (TEM), real-time qPCR, an enzyme assay, and flow cytometry. The results showed that EHP spores, approximately 1 μm in size, were located on the cytoplasm of the hepatopancreas. The number of mitochondria increased significantly, and mitochondria morphology showed a condensed state in the high-concentration EHP-infected shrimp by TEM observation. In addition, there were some changes in mitochondrial potential, but apoptosis was not significantly different in the infected shrimp. The qPCR results showed that the gene expression levels of hexokinase and pyruvate kinase related to energy metabolism were both upregulated in the diseased L. vannamei. Enzymatic activity showed hexokinase and lactate dehydrogenase were significantly increased in the shrimp infected with EHP, indicating EHP infection can increase the glycolysis process and decrease the oxidative phosphorylation process of L. vannamei. Previous transcriptomic data analysis results also support this conclusion.

Informational Analysis and Prediction of Obsessive-Compulsive Disorder Pathogenesis.

We aimed to predict the possible mechanism of obsessive-compulsive disorder (OCD) by integrating and analyzing mRNA sequencing results from two datasets and to provide direction for future studies into the pathogenesis of OCD. Two OCD datasets, GSE78104 and GSE60190, were obtained, and the intersection of the two gene sets with differential expression in OCD samples was selected. Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment and Gene Ontology (GO) analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) online analysis website for the genes at the intersection, and the data were mapped using http://www.bioinformatics.com.cn. After genes with p≤0.05 had been screened out, protein-protein interaction (PPI) interaction analysis was conducted using Metascape to screen the key Molecular Complex Detection (MCODE) genes. MCODE genes were then enriched using the KEGG signaling pathway and GO classification. A total of 3,449 differentially expressed genes (DEGs) were obtained from the GSE78104 and GSE60190 datasets. KEGG, GO, and Gene Set Enrichment Analysis analyses of DEGs showed that the onset of OCD was related to oxidative phosphorylation and other metabolic processes, which may have a similar pathogenesis to other neurodegenerative diseases. Single-gene PPI analysis of SAPAP3 revealed that the mechanism by which SAPAP3 knockout induces OCD may also be caused by affecting oxidative phosphorylation. The mechanism of SAPAP3 knockout-induced OCD in mice may be due to the oxidative phosphorylation process in the body. Future studies on the neural circuit mechanism of OCD should be conducted.

Gouqi-derived nanovesicles (GqDNVs) inhibited dexamethasone-induced muscle atrophy associating with AMPK/SIRT1/PGC1α signaling pathway

With the increasing trend of global aging, sarcopenia has become a significant public health issue. Goji berry, also known as “Gou qi zi” in China, is a traditional Chinese herb that can enhance the structure and function of muscles and bones. Otherwise, previous excellent publications illustrated that plant-derived exosome-like nanoparticles can exert good bioactive functions in different aging or disease models. Thus, we issued the hypothesis that Gouqi-derived nanovesicles (GqDNVs) may also have the ability to improve skeletal muscle health, though the effect and its mechanism need to be explored. Hence, we have extracted GqDNVs from fresh berries of Lycium barbarum L. (goji) and found that the contents of GqDNVs are rich in saccharides and lipids. Based on the pathway annotations and predictions in non-targeted metabolome analysis, GqDNVs are tightly associated with the pathways in metabolism. In muscle atrophy model mice, intramuscular injection of GqDNVs improves the cross-sectional area of the quadriceps muscle, grip strength and the AMPK/SIRT1/PGC1α pathway expression. After separately inhibiting AMPK or PGC1α in C2C12 cells with dexamethasone administration, we have found that the activated AMPK plays the chief role in improving cell proliferation induced by GqDNVs. Furthermore, the energy-targeted metabolome analysis in the quadriceps muscle demonstrates that the GqDNVs up-regulate the metabolism of amino sugar and nucleotide sugar, autophagy and oxidative phosphorylation process, which indicates the activation of muscle regeneration. Besides, the Spearman rank analysis shows close associations between the quality and function of skeletal muscle, metabolites and expression levels of AMPK and SIRT1. In this study, we provide a new founding that GqDNVs can improve the quality and function of skeletal muscle accompanying the activated AMPK/SIRT1/PGC1α signaling pathway. Therefore, GqDNVs have the effect of anti-aging skeletal muscle as a potential adjuvant or complementary method or idea in future therapy and research.Graphical

Thermodynamic analysis of energy coupling by determination of the Onsager phenomenological coefficients for a 3×3 system of coupled chemical reactions and transport in ATP synthesis and its mechanistic implications

The nonequilibrium coupled processes of oxidation and ATP synthesis in the fundamental process of oxidative phosphorylation (OXPHOS) are of vital importance in biosystems. These coupled chemical reaction and transport bioenergetic processes using the OXPHOS pathway meet >90% of the ATP demand in aerobic systems. On the basis of experimentally determined thermodynamic OXPHOS flux-force relationships and biochemical data for the ternary system of oxidation, ion transport, and ATP synthesis, the Onsager phenomenological coefficients have been computed, including an estimate of error. A new biothermokinetic theory of energy coupling has been formulated and on its basis the thermodynamic parameters, such as the overall degree of coupling, q and the phenomenological stoichiometry, Z of the coupled system have been evaluated. The amount of ATP produced per oxygen consumed, i.e. the actual, operating P/O ratio in the biosystem, the thermodynamic efficiency of the coupled reactions, η, and the Gibbs free energy dissipation, Φ have been calculated and shown to be in agreement with experimental data. At the concentration gradients of ADP and ATP prevailing under state 3 physiological conditions of OXPHOS that yield Vmax rates of ATP synthesis, a maximum in Φ of ∼0.5J(hmgprotein)−1, corresponding to a thermodynamic efficiency of ∼60% for oxidation on succinate, has been obtained. Novel mechanistic insights arising from the above have been discussed. This is the first report of a 3 × 3 system of coupled chemical reactions with transport in a biological context in which the phenomenological coefficients have been evaluated from experimental data.

Investigating the role of mitochondrial membrane potential in paternal inheritance of mitochondria

Abstract The process of oxidative phosphorylation (OXPHOS) in mitochondria depends on an electrochemical gradient known as the mitochondrial membrane potential (Δψm). Reflecting high functionality, elevated Δψm usually depicts healthy mitochondria and contributes to organelle selection. This study investigates whether mitochondrial properties linked with bioenergetics, such as Δψm, play a role in paternal inheritance of mitochondria. More specifically, the study looks at how sperm Δψm responds to egg chemoattractants in bivalves characterized by distinct mitochondrial inheritance patterns: strict maternal inheritance (SMI) and doubly uniparental inheritance (DUI), the latter displaying sex-specific transmission of paternal mitochondrial DNA. Sperm Δψm was examined in four bivalve species: the blue mussel (Mytilus edulis) and the Manila clam (Ruditapes philippinarum) (DUI), plus the hard clam (Mercenaria mercenaria) and the soft-shell clam (Mya arenaria) (SMI). In the absence of egg chemoattractants, sperm Δψm did not vary between the two groups. However, there was a trend of increase in Δψm following egg detection only in sperm bearing paternally derived mitochondria (DUI). This suggests, along with bioenergetic changes, that Δψm modulation might be a specific property of at least some DUI species, possibly implicated in their unique ability to transmit their mitochondria in a sex-specific fashion.

THE EFFECT OF ALKALOID SONGORINE ON MITOCHONDRIAL RESPIRATORY RATE AND OXIDATIVE PHOSPHORYLATION PROCESS UNDER NORMAL AND SHORT-TERM STRESS

Stress conditions adversely affect normal physiological functions, resulting in cellular dysfunctions and alterations in molecular mechanisms. Mitochondria, multifunctional organelles within cells, play crucial roles across various aspects of cell physiology, beyond their role in ATP synthesis. Among the biologically active substances, the diterpene alkaloid songorine has an activating effect on the rate of respiration and on the processes of oxidative phosphorylation of normal and stress-induced mitochondria in vitro.

Comparative antioxidant and metabolomic analysis for the identification of differential response of mussel (Mytilus coruscus) to four succinate dehydrogenase inhibitor fungicides.

Succinate dehydrogenase inhibitor fungicides (SDHIs) are frequently detected in the marine environment. However, studies on the toxicity of SDHIs to marine organisms, Mytilus coruscus (M. coruscus), are poorly reported. Therefore, the antioxidant activities and metabolomic response of four SDHIs, namely, boscalid (BC), thifluzamide (TF), fluopyram (FO), and bixafen (BIX), to (M. coruscus), were comprehensively investigated. The antioxidant activity of BC and TF was significantly increased (p<0.05), whereas those of FO and BIX were significantly decreased. Furthermore, metabolite discriminations among M. coruscus to four SDHIs were illustrated by an untargeted metabolomics approach. A total of 52, 50, 93, and 129 differential metabolites were obtained for BC, TF, FO, and BIX. KEGG of the different metabolites show that the four SDHIs had differential effects on the metabolic pathways of M. coruscus. The current study demonstrated four SDHIs triggered glucose metabolism, lipid metabolism, tricarboxylic acid cycle, and oxidative phosphorylation processes and caused the disruption of nutrient and energy conversion processes in mussels. Finally, five biomarkers were screened by analyzing common differential metabolites that emerged from the four SDHI exposures, which could be used for risk assessment of marine ecosystem exposure to SDHIs. Our results demonstrated the use of metabolomics to understand the potential mechanisms of toxicity of four SDHIs to mussels and to identify potential targets for future targeted risk assessment.