Mitochondrial Enzyme Activities Research Articles

A Scoping Review Investigating the "Gene-Dosage Theory" of Mitochondrial DNA in the Healthy Skeletal Muscle.

This review provides an overview of the evidence regarding mtDNA and valid biomarkers for assessing mitochondrial adaptions. Mitochondria are small organelles that exist in almost all cells throughout the human body. As the only organelle, mitochondria contain their own DNA, mitochondrial DNA (mtDNA). mtDNA-encoded polypeptides are subunits of the enzyme complexes in the electron transport chain (ETC) that are responsible for production of ATP to the cells. mtDNA is frequently used as a biomarker for mitochondrial content, since changes in mitochondrial volume are thought to induce similar changes in mtDNA. However, some exercise studies have challenged this "gene-dosage theory", and have indicated that changes in mitochondrial content can adapt without changes in mtDNA. Thus, the aim of this scoping review was to summarize the studies that used mtDNA as a biomarker for mitochondrial adaptions and address the question as to whether changes in mitochondrial content, induce changes in mtDNA in response to aerobic exercise in the healthy skeletal muscle. The literature was searched in PubMed and Embase. Eligibility criteria included: interventional study design, aerobic exercise, mtDNA measurements reported pre- and postintervention for the healthy skeletal muscle and English language. Overall, 1585 studies were identified. Nine studies were included for analysis. Eight out of the nine studies showed proof of increased oxidative capacity, six found improvements in mitochondrial volume, content and/or improved mitochondrial enzyme activity and seven studies did not find evidence of change in mtDNA copy number. In conclusion, the findings imply that mitochondrial adaptions, as a response to aerobic exercise, can occur without a change in mtDNA copy number.

Intraoperative Hemi-Diaphragm Electrical Stimulation Demonstrates Attenuated Mitochondrial Function without Change in Oxidative Stress in Cardiothoracic Surgery Patients.

Mechanical ventilation during cardiothoracic surgery is life-saving but can lead to ventilator-induced diaphragm dysfunction (VIDD) and prolong ventilator weaning and hospital length of stay. Intraoperative phrenic nerve stimulation may preserve diaphragm force production to offset VIDD; we also investigated changes in mitochondrial function after stimulation. During cardiothoracic surgeries (n = 21), supramaximal, unilateral phrenic nerve stimulation was performed every 30 min for 1 min. Diaphragm biopsies were collected after the last stimulation and analyzed for mitochondrial respiration in permeabilized fibers and protein expression and enzymatic activity of biomarkers of oxidative stress and mitophagy. Patients received, on average, 6.2 ± 1.9 stimulation bouts. Stimulated hemidiaphragms showed lower leak respiration, maximum electron transport system (ETS) capacities, oxidative phosphorylation (OXPHOS), and spare capacity compared with unstimulated sides. There were no significant differences between mitochondrial enzyme activities and oxidative stress and mitophagy protein expression levels. Intraoperative phrenic nerve electrical stimulation led to an acute decrease of mitochondrial respiration in the stimulated hemidiaphragm, without differences in biomarkers of mitophagy or oxidative stress. Future studies warrant investigating optimal stimulation doses and testing post-operative chronic stimulation effects on weaning from the ventilator and rehabilitation outcomes.

Esterase Specific Fluorescent Probe: Mechanistic Understanding Using QM/MM Calculation and Cell States Discrimination.

Esterases enzymes regulate the body's homeostasis by catalyzing the hydrolysis of various esters. These are also involved in protein metabolism, detoxification, and signal transmission. Most importantly, esterase plays a significant role in cell viability and cytotoxicity assays. Hence, developing an efficient chemical probe is essential for monitoring the esterase activity. Several fluorescent probes for esterase have also been reported targeting cytosol and lysosomes. However, the ability to create efficient probes is constrained due to a lack of understanding of the esterase's active site for hydrolyzing the substrate. In addition, the fluorescent turn-on may limit efficient monitoring. Herein, we have developed a unique fluorescent probe, PM-OAc, to monitor mitochondrial esterase enzyme activity ratiometrically. This probe exhibited a bathochromic wavelength shift with esterase enzyme in alkaline pH (pH∼8.0) due to an intramolecular charge transfer (ICT) process. The phenomenon is well supported by TD-DFT calculation. Moreover, the substrate (PM-OAc) binding at the active site of esterase and its catalytic mechanism to hydrolyze the ester bond are elucidated by molecular dynamics (MD) simulation and QM/MM (Quantum mechanics/molecular mechanics) calculations, respectively. Fluorescent image-based analysis of the cellular environment reveals that our probe can distinguish between live and dead cells based on esterase enzyme activity.

The cardioprotective effect of human glucagon-like peptide-1 receptor agonist (semaglutide) on cisplatin-induced cardiotoxicity in rats: Targeting mitochondrial functions, dynamics, biogenesis, and redox status pathways.

The cardiotoxic effect of chemotherapeutic agents as cisplatin has become a major issue recently. Interference with mitochondrial dynamics, biogenesis, redox status, and apoptosis are the most possible underlying mechanisms. Semaglutide is a human glucagon-like peptide-1 receptor agonist (GLP-1R), which is used primarily for the treatment of DM. Various recent studies have investigated (GLP-1R) role in cardiovascular diseases due to antiapoptotic and antioxidant effects. The current study aimed to investigate the curative role of semaglutide's against cisplatin- induced cardiotoxicity and its relation to mitochondrial functions, dynamics, biogenesis, apoptosis, and redox status pathways. The study included 30 male rats divided into three groups: control, cisplatin-induced cardiotoxicity, and cisplatin-induced cardiotoxicity treated with semaglutide. At the end of the experiment heart index, serum cardiotoxicity markers, SOD, GPX activities and H2 O2 level were estimated. Mitochondrial transmembrane potential, complex I and citrate synthase enzyme activities, ATP level, Mfn2 in addition to PGC-1 α levels were assessed as biogenesis markers. Mitophagy markers PINK1 and Parkin mRNA gene expression were estimated. Histopathological examination of cardiac muscles of all studied groups and immunoassay of P53 and caspase 3 in cardiac tissue were examined to assess apoptosis. Cisplatin has disturbed mitochondrial function and dynamics, dysregulate redox status and induced mitophagy and apoptosis, in the other hand semaglutide treatment has normalized dysregulated mitochondrial function and dynamics, redox status and suppressed mitophagy and apoptosis. Semaglutide has ameliorative effect against cisplatin- induced cardiotoxicity via modulation of mitochondrial functions, dynamics, biogenesis, apoptosis, and redox status pathways.

Physical activity for cognitive health promotion: An overview of the underlying neurobiological mechanisms.

Physical activity is one of the modifiable factors of cognitive decline and dementia with the strongest evidence. Although many influential reviews have illustrated the neurobiological mechanisms of the cognitive benefits of physical activity, none of them have linked the neurobiological mechanisms to normal exercise physiology to help the readers gain a more advanced, comprehensive understanding of the phenomenon. In this review, we address this issue and provide a synthesis of the literature by focusing on five most studied neurobiological mechanisms. We show that the body's adaptations to enhance exercise performance also benefit the brain and contribute to improved cognition. Specifically, these adaptations include, 1), the release of growth factors that are essential for the development and growth of neurons and for neurogenesis and angiogenesis, 2), the production of lactate that provides energy to the brain and is involved in the synthesis of glutamate and the maintenance of long-term potentiation, 3), the release of anti-inflammatory cytokines that reduce neuroinflammation, 4), the increase in mitochondrial biogenesis and antioxidant enzyme activity that reduce oxidative stress, and 5), the release of neurotransmitters such as dopamine and 5-HT that regulate neurogenesis and modulate cognition. We also discussed several issues relevant for prescribing physical activity, including what intensity and mode of physical activity brings the most cognitive benefits, based on their influence on the above five neurobiological mechanisms. We hope this review helps readers gain a general understanding of the state-of-the-art knowledge on the neurobiological mechanisms of the cognitive benefits of physical activity and guide them in designing new studies to further advance the field.

Cardioprotective potential of mitochondria-targeted antioxidant, mito-TEMPO, in 5-fluorouracil-induced cardiotoxicity

PurposeThe mitochondria-targeted antioxidants (MTAs) are known to offer protection against mitochondrial oxidative stress. The recent evidences support their role in mitigating oxidative stress-induced diseases, including cancer. Therefore, this study investigated cardioprotective potential of mito-TEMPO against 5-FU-induced cardiotoxicity.MethodsMito-TEMPO was administered to male BALB/C mice (intraperitoneally, 0.1 mg/kg b.w. for 7 days) followed by intraperitoneal administration of 5- FU (12 mg/kg b.w. for 4 days). During this period, mito-TEMPO treatment was also continued. The cardioprotective potential of mito-TEMPO was assessed by evaluating cardiac injury markers, extent of non-viable myocardium and histopathological alterations. Mitochondrial functional status and mitochondrial oxidative stress were assessed in cardiac tissue. 8-OHdG expression and apoptotic cell death were assessed using immunohistochemical techniques.ResultsThe level of cardiac injury markers CK-MB and AST were significantly (P ≤ 0.05) decreased in mito-TEMPO pre-protected group which was further reflected in histopathology as decrease in the percentage of non-viable myocardial tissue, disorganization, and loss of myofibrils. Mito-TEMPO ameliorated mtROS, mtLPO and conserved mitochondrial membrane potential. Further, it had significantly (P ≤ 0.05) improved the activity of mitochondrial complexes and mitochondrial enzymes. A significant (P ≤ 0.05) increase in the level of mtGSH, activity of mitochondrial glutathione reductase, glutathione peroxidase, and mitochondrial superoxide dismutase was observed. A decreased expression of 8-OHdG and reduced apoptotic cell death were observed in mito-TEMPO pre-protected group.ConclusionMito-TEMPO effectively mitigated 5-FU-induced cardiotoxicity by modulating mitochondrial oxidative stress, hence may serve as a protective agent/adjuvant in 5-FU-based combinatorial chemotherapy.

Acute Ozone-Induced Transcriptional Changes in Markers of Oxidative Stress and Glucocorticoid Signaling in the Rat Hippocampus and Hypothalamus Are Sex-Specific.

Exposure to a prototypic air pollutant ozone (O3) has been associated with the activation of neuroendocrine stress response along with neural changes in oxidative stress (OS), inflammation, and Alzheimer's disease-like pathologies in susceptible animal models. We hypothesized that neural oxidative and transcriptional changes induced by O3 in stress responsive regions are sex-dependent. Male and female adult Long-Evans rats were exposed to filtered air or O3 for two consecutive days (0.8 ppm, 4 h/day) and brain regions were flash-frozen. Activities of cerebellar OS parameters and mitochondrial complex I, II, and IV enzymes were assessed to confirm prior findings. We assessed transcriptional changes in hypothalamus (HYP) and hippocampus (HIP) for markers of OS, microglial activity and glucocorticoid signaling using qPCR. Although there were no O3 or sex-related differences in the cerebellar activities of OS and mitochondrial enzymes, the levels of protein carbonyls and complex II activities were higher in females regardless of O3. There were no statistical differences in baseline expression of genes related to OS (Cat, Dhcr24, Foxm1, Gpx1, Gss, Nfe2l2, Sod1) except for lower HYP Sod1 expression in air-exposed females than males, and higher HIP Gss expression in O3-exposed females relative to matched males. Microglial marker Aif1 expression was higher in O3-exposed females relative to males; O3 inhibited Itgam only in males. The expression of Bdnf in HIP and HYP was inhibited by O3 in both sexes. Genes related to glucocorticoid signaling (Fkbp4, Fkbp5, Hsp90aa1, Hspa4, nr3c1, nr3c2) showed sex-specific effects due to O3 exposure. Baseline expression of HIP Fkbp4 was higher in females relative to males. O3 inhibited Nr3c1 in female HIP and male HYP, but Nr3c2 was inhibited in male HYP. Fkbp4 expression was higher in O3-exposed females when compared to matched males, whereas Fkbp5 was expressed at higher levels in both brain regions of males and females. These results indicate that sex-specific brain region responses to O3 might, in part, be caused by OS and regulation of glucocorticoid signaling.

Mannose delays senescence in broccoli florets via maintaining mitochondrial morphological structure and function

The influence of mannose treatment on mitochondrial physiological parameters was investigated to postpone broccoli senescence. The results showed that mannose treatment could reduce the level of mitochondrial reactive oxygen species (ROS) to slow down the damage to its ultrastructure. Mannose inhibited malondialdehyde (MDA) accumulation and the decline of cytochrome c/a (Cyt c/a), and delayed the increase of mitochondrial membrane permeability. It also alleviated the over-opening of the mitochondrial membrane permeability transition pore (MPTP) by regulating expressions of MPTP component genes such as BoVDAC, BoHXK and BoANT. Moreover, mannose treatment improved the activities of mitochondrial antioxidant enzymes, including ascorbate oxidase (APX), superoxide dismutase (SOD), catalase (CAT), and ascorbic acid (AsA) content. Also, it increased the activities of succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and Ca2+-ATPase, which were crucial for the mitochondrial energy metabolism. Taken together, our data indicated that mannose treatment inhibited the senescence of broccoli by maintaining the mitochondrial morphological structure and function.

Dietary patterns and fertility status in men: Mediterranean diet does make a difference in ameliorating the rise in male infertility problems due to changing lifestyle

Dietary patterns and fertility status in men: Mediterranean diet does make a difference in ameliorating the rise in male infertility problems due to changing lifestyle

The role of the mechanistic target of rapamycin complex 1 in the regulation of mitochondrial adaptation during skeletal muscle atrophy under denervation or calorie restriction in mice.

Mechanistic target of rapamycin complex 1 (mTORC1) is a protein complex that regulates skeletal muscle protein synthesis and hypertrophy. mTORC1-mediated signaling activities are activated during denervation-induced skeletal muscle atrophy and suppressed during calorie restriction-induced atrophy. Mitochondria control the qualitative plasticity of skeletal muscles primarily through biogenesis, fusion, and fission. We recently showed that mTORC1 activation contributes toward mitochondrial homeostasis. In this study, we examined the role of mTORC1 in mitochondrial adaptation during denervation- or calorie restriction-induced skeletal muscle atrophy. Seven-week-old Institute of Cancer Research mice were subjected to 14 days of denervation or calorie restriction combined with the administration of the mTORC1 inhibitor-"rapamycin". Our results showed that although mTORC1 inhibition did not alter mitochondrial biogenesis, content and enzyme activity, it suppressed the activation of dynamin-related protein 1 (DRP1), a mitochondrial fission-related protein in denervated muscle, and reduced DRP1 expression in calorie-restricted muscle. Furthermore, calorie restriction-induced mitochondrial fragmentation was partially suppressed by mTORC1 inhibition. Taken together, our results indicate that mTORC1 activation upon denervation and inhibition upon calorie restriction contributes to qualitative changes in muscle plasticity by at least partially regulating the mitochondrial fission response.

De novo frameshift variant in MT-ND1 causes a mitochondrial complex I deficiency associated with MELAS syndrome

BackgroundThe variant m.3571_3572insC/MT-ND1 thus far only reported in oncocytic tumors of different tissues. However, the role of m.3571_3572insC in inherited mitochondrial diseases has yet to be elucidated. MethodsA patient diagnosed with MELAS syndrome was recruited, and detailed medical records were collected and reviewed. The muscle was biopsied for mitochondrial respiratory chain enzyme activity. Series of fibroblast clones bearing different m.3571_3572insC variant loads were generated from patient-derived fibroblasts and subjected to functional assays. ResultsComplex I deficiency was confirmed in the patient’s muscle via mitochondrial respiratory chain enzyme activity assay. The m.3571_3572insC was filtered for the candidate variant of the patient according to the guidelines for mitochondrial mRNA variants interpretation. Three cell clones with different m.3571_3572insC variant loads were generated to evaluate mitochondrial function. Blue native PAGE analysis revealed that m.3571_3572insC caused a deficiency in the mitochondrial complex I. Oxygen consumption rate, ATP production, and lactate assays found an impairment of cellular bioenergetic capacity due to m.3571_3572insC. Mitochondrial membrane potential was decreased, and mitochondrial reactive oxygen species production was increased with the variant of m.3571_3572insC. According to the competitive cell growth assay, the mutant cells had impaired cell growth capacity compared to wild type. ConclusionsA novel variant m.3571_3572insC was identified in a patient diagnosed with MELAS syndrome, and the variant impaired mitochondrial respiration by decreasing the activity of complex I. In conclusion, the genetic spectrum of mitochondrial diseases was expanded by including m.3571_3572insC/MT-ND1.

Impact of Coenzyme Q10 Supplementation on Skeletal Muscle Respiration, Antioxidants, and the Muscle Proteome in Thoroughbred Horses.

Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial electron transfer system and a potent antioxidant. The impact of CoQ10 supplementation on mitochondrial capacities and the muscle proteome is largely unknown. This study determined the effect of CoQ10 supplementation on muscle CoQ10 concentrations, antioxidant balance, the proteome, and mitochondrial respiratory capacities. In a randomized cross-over design, six Thoroughbred horses received 1600 mg/d CoQ10 or no supplement (control) for 30-d periods separated by a 60-d washout. Muscle samples were taken at the end of each period. Muscle CoQ10 and glutathione (GSH) concentrations were determined using mass spectrometry, antioxidant activities by fluorometry, mitochondrial enzyme activities and oxidative stress by colorimetry, and mitochondrial respiratory capacities by high-resolution respirometry. Data were analyzed using mixed linear models with period, supplementation, and period × supplementation as fixed effects and horse as a repeated effect. Proteomics was performed by tandem mass tag 11-plex analysis and permutation testing with FDR < 0.05. Concentrations of muscle CoQ10 (p = 0.07), GSH (p = 0.75), and malondialdehyde (p = 0.47), as well as activities of superoxide dismutase (p = 0.16) and catalase (p = 0.66), did not differ, whereas glutathione peroxidase activity (p = 0.003) was lower when horses received CoQ10 compared to no supplement. Intrinsic (relative to citrate synthase activity) electron transfer capacity with complex II (ECII) was greater, and the contribution of complex I to maximal electron transfer capacity (FCRPCI and FCRPCIG) was lower when horses received CoQ10 with no impact of CoQ10 on mitochondrial volume density. Decreased expression of subunits in complexes I, III, and IV, as well as tricarboxylic acid cycle (TCA) enzymes, was noted in proteomics when horses received CoQ10. We conclude that with CoQ10 supplementation, decreased expression of TCA cycle enzymes that produce NADH and complex I subunits, which utilize NADH together with enhanced electron transfer capacity via complex II, supports an enhanced reliance on substrates supplying complex II during mitochondrial respiration.

The neuroprotective effect of betanin nanoparticles on brain ischemia–reperfusion injury

BackgroundBetanin is an antioxidant and anti-inflammatory compound that has attracted the attention of researchers in a variety of diseases in recent years. Therefore, In the present study the effect of pretreatment of betanin nanoparticles (NB) in cerebral ischemia rats was investigated. MethodsOral administration of NB started five days before bilateral common carotid artery occlusion (BCCAO) induction and continued for three days thereafter in rats. The neurological disorder scores (NDS), brain swelling and edema were evaluated. After preparing brain homogenate, the intensity of oxidative stress, the activities of antioxidant enzymes, GSH content, the activities of mitochondrial enzymes SDH, MDH and LDH were studied. Also, the expressions of IL-1β, IL-6, TNF-α cytokines were measured. The expression levels of NF-ĸB and pSTAT3 genes and proteins and ERK and TFEB proteins were also studied. ResultsNB showed strong anti-inflammatory and antioxidant effects in cerebral I/R rats and improved mitochondrial and antioxidant enzymes activities. Decreases in NDS, swelling and edema of the brain were also observed in the cerebral I/R rats receiving NB. Also, administration of NB decreased the expressions of inflammatory cytokines and upregulated the expressions of NF-KB and pSTAT3 genes and proteins and overexpressed ERK and TEFB proteins. ConclusionNB has neuroprotective effects in cerebral I/R condition due to its antioxidant and anti-inflammation properties, which can be considered as a suitable treatment option in stroke conditions.

Restricted physical activity after volumetric muscle loss alters whole-body and local muscle metabolism.

Volumetric muscle loss (VML) is the traumatic loss of skeletal muscle, resulting in chronic functional deficits and pathological comorbidities, including altered whole-body metabolic rate and respiratory exchange ratio (RER), despite no change in physical activity in animal models. In other injury models, treatment with β2 receptor agonists (e.g. formoterol) improves metabolic and skeletal muscle function. We aimed first to examine if restricting physical activity following injury affects metabolic and skeletal muscle function, and second, to enhance the metabolic and contractile function of the muscle remaining following VML injury through treatment with formoterol. Adult male C57Bl/6J mice (n=32) underwent VML injury to the posterior hindlimb compartment and were randomly assigned to unrestricted or restricted activity and formoterol treatment or no treatment; age-matched injury naïve mice (n=4) were controls for biochemical analyses. Longitudinal 24h evaluations of physical activity and whole-body metabolism were conducted following VML. In vivo muscle function was assessed terminally, and muscles were biochemically evaluated for protein expression, mitochondrial enzyme activity and untargeted metabolomics. Restricting activity chronically after VML had the greatest effect on physical activity and RER, reflected in reduced lipid oxidation, although changes were attenuated by formoterol treatment. Formoterol enhanced injured muscle mass, while mitigating functional deficits. These novel findings indicate physical activity restriction may recapitulate following VML clinically, and adjunctive oxidative treatment may create a metabolically beneficial intramuscular environment while enhancing the injured muscle's mass and force-producing capacity. Further investigation is needed to evaluate adjunctive oxidative treatment with rehabilitation, which may augment the muscle's regenerative and functional capacity following VML. KEY POINTS: The natural ability of skeletal muscle to regenerate and recover function is lost following complex traumatic musculoskeletal injury, such as volumetric muscle loss (VML), and physical inactivity following VML may incur additional deleterious consequences for muscle and metabolic health. Modelling VML injury-induced physical activity restriction altered whole-body metabolism, primarily by decreasing lipid oxidation, while preserving local skeletal muscle metabolic activity. The β2 adrenergic receptor agonist formoterol has shown promise in other severe injury models to improve regeneration, recover function and enhance metabolism. Treatment with formoterol enhanced mass of the injured muscle and whole-body metabolism while mitigating functional deficits resulting from injury. Understanding of chronic effects of the clinically available and FDA-approved pharmaceutical formoterol could be a translational option to support muscle function after VML injury.

Renin-angiotensin system in the central nervous system: focus on Huntington's disease.

Renin-angiotensin system in the central nervous system: focus on Huntington's disease.

Effects of sophoroflavonoside and narcissin flavonoids on mitochondrial dysfunction and antioxidant enzyme activity in rat liver poisoned with galoxyfop-r-methyl pesticide

This study delves into the accumulation of residues in the liver tissue of rats exposed to the galoxyfop-R-methyl pesticide. The investigation also evaluates the presence of malondialdehyde (MDA), a lipid peroxidation (LPO) product, in the liver mitochondrial membrane, along with the activity of antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GP). The study further explores the impact of sophoraflavonoloside (SFL) and narcissin flavonoids on enzyme activity over a dynamic span of 10 to 40 days. In the experimental design, rats in the study group were subjected to galoxyfop-R-methyl pesticide at a dosage equivalent to LD50/10 through a specialized probe. Subsequently, the concentration of the pesticide residues in liver tissue was measured on the 5th, 10th, 20th, 30th, and 40th days post-pesticide exposure. The research also probes into the content of malondialdehyde (MDA) in the liver mitochondrial membrane, as well as the activity of antioxidant enzymes, within the context of SFL. This meticulous examination aids in comprehending the dynamics of enzyme responses and oxidative stress modulation in the liver of rats subjected to galoxyfop-R-methyl pesticide. By investigating the intricate interactions between pesticide exposure, enzyme activity, and antioxidant mechanisms, this study contributes to the broader understanding of the potential effects and counteractive measures concerning pesticide-related challenges in biological systems.

НЕКОТОРЫЕ МОРФОФУНКЦИОНАЛЬНЫЕ ОСОБЕННОСТИ МИТОХОНДРИЙ, ИХ СВЯЗЬ С РЕПРОДУКТИВНОЙ ФУНКЦИЕЙ ЖЕНЩИН

Introduction. Mitochondrial morphology and metabolism can have a decisive influence on energy metabolism and reproductive function in women. The objective of this study is to characterize the metabolic and energy metabolism processes in women of reproductive age and those in perimenopause. Methods. The study involved 100 women divided into two equal groups: women of reproductive age and women in perimenopause. Results. All participants had regular menstrual cycles. The duration of menopause in the second group was 1-3 years, with an onset age of 45 years. In total, 64% of the women in group 2 had neurohumoral abnormalities and obesity. Moderate to severe menopause symptoms were detected in 56% of women. Group 2 had reduced activity of mitochondrial enzymes in lymphocytes, such as succinate dehydrogenase and α-glycerophosphate dehydrogenase, while protein, glucose, and uric acid were above normal. Conclusion. This finding suggests that mitochondrial enzymes in group 2 become less active with age. At the end of the reproductive age, the intensity of the energy processes decreases. Cell energy metabolism remains an important area as further research, as this process can shift the timing of reproductive aging in women.

Differential manifestation of RONS and antioxidant enzymes in response to singular versus combinatorial stress in Chironomus ramosus

In nature, organisms face multiple abiotic stress concurrently. Our previous study has indicated how threshold level of lethality depends on the type and combination of stressors. Many mechanisms exist by which organisms respond to stressors and maintain homeostasis. We examined the homeostatic pliability in an extremophilic oriental midge Chironomus ramosus larvae under various combinatorial stress conditions of desiccation (DS), heat (HS) and starvation (SS). Exposure to these stressors led to activation of a common response pathway of oxidative stress. Abundance of antioxidant enzymes like superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase along with selective as well as stressor specific increase in total antioxidant capacity were reflected from the corresponding level of reactive oxygen and nitrogen species (RONS) in larvae exposed to various combinatorial stress. Additionally, we found stressor specific increment in lipid peroxidation level, protein carbonyl content and advanced oxidative protein products during the stress regime. Further investigation revealed a sharp decline in the activity of mitochondrial aconitase enzyme activity in response to abiotic stress induced oxidative stress. The combinatorial stressor specific comparative study based on biochemical and fluorescence based redox-endpoint assays confirmed that the generation of oxidative stress is the consequential convergent pathway of DS, HS and SS, but the quantum of RONS decides the redox potential of homeostatic response and survival rate.

Comparative assessment of the effect of titanium dioxide – based nanoparticles on boar germ cells in vitro

Modern titanium dioxide nanomaterials, in particular modified with nanosilver, have antiviral, antibacterial, antifungal activity, cytotoxic effects in vitro experiments and can affect germ cells of warm-blooded laboratory animals. The research aims to study the effect of different types of titanium dioxide nanoparticles on the physiological and biochemical characteristics of wild boar germ cells in vitro. When applying the maximum dose (LD50) of the studied nanopowders in all samples, sperm survival was probably lower than in the control: by 41.9% (р&lt;0.001) ‒ under the action of TiO2 nanoparticles (hereinafter NPs) (Frantsevich Institute for Problems of Materials Science of NAS of Ukraine, hereinafter IPM), by 28.0% (р&lt;0.05) ‒ under the action of TiO2 NPs (Acros Organics), by 53.5% (р&lt;0.001) ‒ under the action of 4% Ag-TiO2 NPs (IPM) and by 55.9% (р&lt;0.001) ‒ are the action of NPs 8% Ag-TiO2 (IPM). Nanopowders of different based on titanium dioxide manufacturers, characterized by similar morphological characteristics and varying degrees of nanosilver addition (Ag content from 0 to 8%), starting from a dose of 1/10 LD50, can have a damaging effect on the germ cells of wild boars, which is manifested by a decrease in the respiratory activity of sperm and cytochrome oxidase activity, by increasing succinate dehydrogenase activity. The most sensitive marker was the sperm survival rate, the value of which significantly decreased under the action of 8% Ag-TiO2 nanoparticles (IPM) at a dose of 1/100 LD50, which is a consequence of disruption of the activity of mitochondrial enzymes and, accordingly, resynthesis of ATP. Our results confirm and extend the data on the nature of the damaging effect of titanium dioxide-based nanoparticles on germ cells of warm-blooded animals due to oxidative stress. The obtained experimental data will be taken into account in the hygienic regulation of the investigated nanopowders.

The unbroken Krebs cycle. Hormonal-like regulation and mitochondrial signaling to control mitophagy and prevent cell death.

The tricarboxylic acid (TCA) or Krebs cycle, which takes place in prokaryotic cells and in the mitochondria of eukaryotic cells, is central to life on Earth and participates in key events such as energy production and anabolic processes. Despite its relevance, it is not perceived as tightly regulated compared to other key metabolisms such as glycolysis/gluconeogenesis. A better understanding of the functioning of the TCA cycle is crucial due to mitochondrial function impairment in several diseases, especially those that occur with neurodegeneration. This article revisits what is known about the regulation of the Krebs cycle and hypothesizes the need for large-scale, rapid regulation of TCA cycle enzyme activity. Evidence of mitochondrial enzyme activity regulation by activation/deactivation of protein kinases and phosphatases exists in the literature. Apart from indirect regulation via G protein-coupled receptors (GPCRs) at the cell surface, signaling upon activation of GPCRs in mitochondrial membranes may lead to a direct regulation of the enzymes of the Krebs cycle. Hormonal-like regulation by posttranscriptional events mediated by activable kinases and phosphatases deserve proper assessment using isolated mitochondria. Also see the video abstract here: https://youtu.be/aBpDSWiMQyI.