Guillermo Lopez-Lluch (0000-0001-9830-8502)

Tropomyosin (TM) is a pan-allergen with cross-reactivity to arthropods, insects, and nematodes in tropical regions. While IgE epitopes of TM contribute to sensitization, T-cell (MHC-II) epitopes polarize the Th2 immune response. This study aimed to identify linear B and T consensus epitopes among house dust mites, cockroaches, Ascaris lumbricoides, shrimp, and mosquitoes, exploring the molecular basis of cross-reactivity in allergic diseases. Amino acid sequences of Der p 10, Der f 10, Blo t 10, Lit v 1, Pen a 1, Pen m 1, rAsc l 3, Per a 7, Bla g 7, and Aed a 10 were collected from Allergen Nomenclature and UniProt. B epitopes were predicted using AlgPred 2.0 and BepiPred 3.0. T epitopes were predicted with NetMHCIIpan 4.1 against 10 HLA-II alleles. Consensus epitopes were obtained through analysis and Epitope Cluster Analysis in the Immune Epitope Database. We found 7 B-cell epitopes and 28 linear T-cell epitopes binding to MHC II. A unique peptide (residues 160–174) exhibited overlap between linear B-cell and T-cell epitopes, highly conserved across tropomyosin sequences. These findings shed light on IgE cross-reactivity among the tested species. The described immuno-informatics pipeline and epitopes can inform in vitro research and guide synthetic multi-epitope proteins’ design for potential allergology immunotherapies. Further in silico studies are warranted to confirm epitope accuracy and guide future experimental protocols.

Coenzyme Q (CoQ) is a lipidic compound that is widely distributed in nature, with crucial functions in metabolism, protection against oxidative damage and ferroptosis and other processes. CoQ biosynthesis is a conserved and complex pathway involving several proteins. COQ2 is a member of the UbiA family of transmembrane prenyltransferases that catalyzes the condensation of the head and tail precursors of CoQ, which is a key step in the process, because its product is the first intermediate that will be modified in the head by the next components of the synthesis process. Mutations in this protein have been linked to primary CoQ deficiency in humans, a rare disease predominantly affecting organs with a high energy demand. The reaction catalyzed by COQ2 and its mechanism are still unknown. Here, we aimed at clarifying the COQ2 reaction by exploring possible substrate binding sites using a strategy based on homology, comprising the identification of available ligand-bound homologs with solved structures in the Protein Data Bank (PDB) and their subsequent structural superposition in the AlphaFold predicted model for COQ2. The results highlight some residues located on the central cavity or the matrix loops that may be involved in substrate interaction, some of which are mutated in primary CoQ deficiency patients. Furthermore, we analyze the structural modifications introduced by the pathogenic mutations found in humans. These findings shed new light on the understanding of COQ2’s function and, thus, CoQ’s biosynthesis and the pathogenicity of primary CoQ deficiency.

In this study we investigated the relationship between cognitive reserve (CR) proxies, such as education, physical activity (PA), and cognitive dysfunction (CD) in the presence or absence of frontotemporal disorders (FTD). Previous research has suggested that education and PA may delay the onset of CD and reduce the risk of developing dementia. However, it remains unclear whether these CR proxies can protect against CD when FTD is present. We aimed to explore this relationship and determine whether sustained CR may be evident regardless of FTD. We recruited 149 older adults (aged 65–99 years) from community centers where they were voluntarily participating in leisure activities. We used bioelectrical impedance to measure their body composition, and we administered the International PA Questionnaire and the Mini-Mental State Examination to measure their PA and cognitive function, respectively. We …

BackgroundAdiponectin and leptin are pivotal in the regulation of metabolism. Pediatric lupus nephritis (pLN), a manifestation of childhood systemic lupus erythematosus (SLE) affecting the kidneys, is associated with impaired adipokine levels, suggesting a role in pLN pathogenesis. The aim of this study was to explore the potential relationship between specific single-nucleotide polymorphisms (SNPs)—methylenetetrahydrofolate reductase (MTHFR) rs1801131 and fibrinogen gamma chain (FGG) rs2066865—and the serum levels of leptin and adiponectin in patients with pLN.MethodsNinety-eight pLN patients and one hundred controls were enrolled in the study. Serum leptin and adiponectin levels were measured using ELISA. DNA extraction and real-time PCR genotyping were performed for MTHFR rs1801131 and FGG rs2066865 SNPs.ResultsCompared to healthy controls, pLN patients exhibited significantly …

Coenzyme Q (CoQ) is a lipidic compound widely distributed in nature with crucial functions in metabolism, protection against oxidative damage and ferroptosis, and other processes. CoQ biosynthesis is a conserved and complex pathway involving several proteins. COQ2 is a member of the UbiA family of transmembrane prenyltransferases that catalyzes the condensation of the head and tail precursors of CoQ, a key step in the process because its product is the first intermediate that will be modified in the head by the next component of the synthesis process. Mutations in this protein have been linked to primary CoQ deficiency in humans, a rare disease predominantly affecting organs with a high energy demand. The reaction catalyzed by COQ2 and its mechanism are still unknown. Here we aimed at clarifying COQ2 reaction by exploring possible substrate binding sites using a strategy based on homology, comprising the identification of ligand-bound homologs with solved structures available in the Protein Data Bank (PDB) and their subsequent structural superposition to the AlphaFold predicted model for COQ2. The results highlight some residues located on the central cavity or the matrix loops that may be involved in substrate interaction, some of them mutated in primary CoQ deficiency patients. Furthermore, we analyze the structural modifications introduced by the pathogenic mutations found in humans. These findings shed new light on the understanding of COQ2 function and, thus, CoQ biosynthesis and pathogenicity of primary CoQ deficiency.

Research on the evolution of performance throughout a season in team sports is scarce and mainly focused on men’s teams. Our aim in this study was to examine the seasonal variations in relevant indices of physical performance in female football players. Twenty-seven female football players were assessed at week 2 of the season (preseason, PS), week 7 (end of preseason, EP), week 24 (half-season, HS), and week 38 (end of season, ES). Similar to the most common used conditioning tests in football, testing sessions consisted of (1) vertical countermovement jump (CMJ); (2) 20 m running sprint (T20); (3) 25 m side-step cutting maneuver test (V-CUT); and (4) progressive loading test in the full-squat exercise (V1-LOAD). Participants followed their normal football training procedure, which consisted of three weekly training sessions and an official match, without any type of intervention. No significant time effects were observed for CMJ height (p = 0.29) and T20 (p = 0.11) throughout the season. However, significant time effects were found for V-CUT (p = 0.004) and V1-LOAD (p = 0.001). V-CUT performance significantly improved from HS to ES (p = 0.001). Significant increases were observed for V1-LOAD throughout the season: PS-HS (p = 0.009); PS-ES (p < 0.001); EP-ES (p < 0.001); and HS-ES (p = 0.009). These findings suggest that, over the course of the season, female football players experience an enhancement in muscle strength and change of direction ability. However, no discernible improvements were noted in sprinting and jumping capabilities during the same period.

Brain deterioration with age is associated with inflammation and oxidative stress that result in structural and functional changes. Recent studies have indicated that coenzyme Q10 (CoQ10) is associated with neurological oxidative stress and cognitive impairment. Studies with older people have shown a relationship between neurodegenerative diseases and CoQ10 levels. However, no studies have analyzed the relationship between CoQ10 and cognitive functioning in older adults. The aim of this study was to analyze the association between CoQ10 and cognitive functioning in an older adult sample, controlling for other factors that may influence aging, such as the level of physical activity and nutritional status. The sample consisted of 64 older adults aged 65–99 years (76.67 ± 8.16 years), among whom 48 were women (75%). The participants were recruited among those who attended community centers to …

European Association of Spa Rehabilitation (ESPA) recommends spa rehabilitation for patients with post-COVID-19 syndrome. We tested the hypothesis that a high-altitude environment with clean air and targeted spa rehabilitation (MR — mountain spa rehabilitation) can contribute to the improving platelet mitochondrial bioenergetics, to accelerating patient health and to the reducing socioeconomic problems. Fifteen healthy volunteers and fourteen patients with post-COVID-19 syndrome were included in the study. All parameters were determined before MR (MR1) and 16–18 days after MR (MR2). Platelet mitochondrial respiration and OXPHOS were evaluated using high resolution respirometry method, coenzyme Q10 level was determined by HPLC, and concentration of thiobarbituric acid reactive substances (TBARS) as a parameter of lipid peroxidation was determined spectrophotometrically. This pilot study …

Background: Sorafenib is a tyrosine kinase inhibitor for the treatment of patients at advanced stage of hepatocellular carcinoma (HCC) who cannot benefit from immunotherapy. The induction of cell death and cell cycle arrest is associated with mitochondrial dysfunction in cancer cells. Aim: To characterize the role of oxidative and nitrosative stress in the mitochondrial dysfunction induced by Sorafenib in liver cancer cells.Methods: The impact of MnTBAP, catalase and the scavenger of peroxynitrite FeTTPs was determined in Sorafenib (0-10 μM)-treated HepG2 cells. The nitration of UCP2 was determined in coupled immunoprecipitation and immune blot procedures. Oxygen consumption was determined in permeabilized HepG2 cells or in isolated mitochondria using Oxygraph-2k (Oroboros), as well as in intact cells (Seahorse). Mitochondrial complex activities were determined in isolated mitochondria and cell lysate …

The aim of this study was to examine the seasonal variations in relevant indices of physical performance in female soccer players. Twenty-seven female soccer players were assessed at week 2 of the season (pre-season, PS), week 7 (end of pre-season, EP), week 24 (half-season, HS), and week 38 (end of season, ES). Testing sessions consisted of: 1) vertical countermovement jump (CMJ); 2) 20-m running sprint (T20); 3) 25-m side-step cutting maneuver test (V-CUT); and 4) progressive loading test in the full-squat exercise (V1-LOAD). Participants followed their normal soccer training, which consisted of three weekly training sessions and an official match, without any type of intervention. No significant time effects were observed for CMJ height (P= 0.29) and T20 (P= 0.11) along the season. Significant time effects were found for V-CUT (P= 0.004) and V1-LOAD (P= 0.001). V-CUT performance significantly improved from HS to ES (P= 0.001). Significant increases were observed for V1-LOAD throughout the season: PS-HS (P= 0.009), PS-ES (P < 0.001); EP-ES (P < 0.001); HS-ES (P= 0.009). In conclusion, female adapted soccer training may be effective for increasing muscle strength and change of direction ability. The high volume of endurance-type training typically accumulated throughout the season may prevent any sprint and jump improvements.

Aging is a very complex process in which many factors are involved. As a common factor the accumulation of damaged cell and tissue structures, impair cell activity at different levels ending in the malfunction of organs and cell death. In this process, dysfunctional mitochondria play a very important role. Coenzyme Q is a key factor in the activity of mitochondria and in the protection of cells against lipid peroxidation. Its levels decrease during aging and supplementation improve cell functionality and delay the progression of age-related diseases. In this chapter, the importance of CoQ in aging and the strategies to restore levels in the cell and organs are shown. These strategies can help to improve health during aging and demonstrate that the maintenance of CoQ levels can be considered a good antiaging strategy.

Coq10 and endothelial cells activity: relationship with cognitive deficiency | DIGITAL.CSIC Skip navigation Logo pequeño DigitalCISC Producción CSIC Áreas e Institutos Navegar ítems por: Fecha Publicación Autor Título Palabras Clave Autor con perfil Proyecto de investigación Grupo de investigación Agencia Financiadora Fecha Envío Pasarela Estadísticas Contacto Servicios Mi DIGITAL.CSIC Suscripciones Editar perfil 1.DIGITAL.CSIC 2.Biología y Biomedicina 3.Centro Andaluz de Biología del Desarrollo (CABD) 4.(CABD) Comunicaciones congresos Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/354804 COMPARTIR / EXPORTAR: logo share SHARE BASE Comparte tu historia de Acceso Abierto Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE Refman EndNote Bibtex RefWorks Excel CSV PDF DataCite Send via …

[Results]: Treatment with 1 mM pABA during 3 or 6 days induces a significant decrease in the levels of CoQ10 in all the cells analyzed. This effect is accompanied by changes in the levels of superoxide or hydrogen peroxide. Interestingly, in HCT116 cells the levels of superoxide increased whereas the levels of hydrogen peroxide decreased. No great changes in mitochondrial potential were found although we found markers of an increase of mitochondrial mass although the mitochondrial activity was profoundly decreased probably indicating the accumulation of damaged and inactive mitochondrial structures. The treatment with pABA induced the activation of the ubiquitin-dependent mitophagy process as determined by the increase in PINK1 and PARKIN and changes in p-p62/p62 at the same time that changes in markers of induction of autophagy as the decrease in the LC3II/I ratio and the increase of Beclin-1 and ATG3. On the other hand, the BNIP-NIX-dependent pathway seems to be also affected. In general, the decrease in CoQ10 levels induced by pABA induced changes in the mito/autophagy system that can be influence the behaviour of many diseases.

An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19's pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients.

Background Mitochondrial dysfunction and redox cellular imbalance indicate crucial function in COVID-19 pathogenesis. Since 11 March 2020, a global pandemic, health crisis and economic disruption has been caused by SARS-CoV-2 virus. Vaccination is considered one of the most effective strategies for preventing viral infection. We tested the hypothesis that preventive vaccination affects the reduced bioenergetics of platelet mitochondria and the biosynthesis of endogenous coenzyme Q10 (CoQ10) in patients with post-acute COVID-19. Material and Methods 10 vaccinated patients with post-acute COVID-19 (V + PAC19) and 10 unvaccinated patients with post-acute COVID-19 (PAC19) were included in the study. The control group (C) consisted of 16 healthy volunteers. Platelet mitochondrial bioenergy function was determined with HRR method. CoQ10, γ-tocopherol, α-tocopherol and β-carotene were determined by HPLC, TBARS (thiobarbituric acid reactive substances) were determined spectrophotometrically. Results Vaccination protected platelet mitochondrial bioenergy function but not endogenous CoQ10 levels, in patients with post-acute COVID-19. Conclusions Vaccination against SARS-CoV-2 virus infection prevented the reduction of platelet mitochondrial respiration and energy production. The mechanism of suppression of CoQ10 levels by SARS-CoV-2 virus is not fully known. Methods for the determination of CoQ10 and HRR can be used for monitoring of mitochondrial bioenergetics and targeted therapy of patients with post-acute COVID-19.

Impaired spermatogenesis and male infertility are common manifestations associated with mitochondrial diseases, yet the underlying mechanisms linking these conditions remain elusive. In this study, we demonstrate that mice deficient for the mitochondrial intra-membrane rhomboid protease PARL, a recently reported model of the mitochondrial encephalopathy Leigh syndrome, develop early testicular atrophy caused by a complete arrest of spermatogenesis during meiotic prophase I, followed by degeneration and death of arrested spermatocytes. This process is independent of neurodegeneration. Interestingly, genetic modifications of PINK1, PGAM5, and TTC19–three major substrates of PARL with important roles in mitochondrial homeostasis–fail to reproduce or modify this severe phenotype, indicating that the spermatogenic arrest arises from distinct molecular pathways. We further observed severe abnormalities in mitochondrial ultrastructure in PARL-deficient spermatocytes, along with prominent electron transfer chain defects, disrupted coenzyme Q (CoQ) biosynthesis, and metabolic rewiring. These mitochondrial defects are associated with a germ cell-specific decrease in GPX4 expression leading arrested spermatocytes to ferroptosis–a regulated cell death modality characterized by uncontrolled lipid peroxidation. Our results suggest that mitochondrial defects induced by PARL depletion act as an initiating trigger for ferroptosis in primary spermatocytes through simultaneous effects on GPX4 and CoQ–two major inhibitors of ferroptosis. These findings shed new light on the potential role of ferroptosis in the pathogenesis of mitochondrial …

The variable success in the outcome of randomised controlled trials supplementing coenzyme Q10 (CoQ10) may in turn be associated with a number of currently unresolved issues relating to CoQ10 metabolism. In this article, we have reviewed what is currently known about these factors and where gaps in knowledge exist that need to be further elucidated. Issues addressed include (i) whether the bioavailability of CoQ10 could be improved; (ii) whether CoQ10 could be administered intravenously; (iii) whether CoQ10 could be administered via alternative routes; (iv) whether CoQ10 can cross the blood-brain barrier; (v) how CoQ10 is transported into and within target cells; (vi) why some clinical trials supplementing CoQ10 may have been unsuccessful; and (vii) which is the most appropriate tissue for the clinical assessment of CoQ10 status.

ADCK2 is involved in fatty acid metabolism and Coenzyme Q (CoQ) biosynthesis Haploinsufficiency of ADCK2 in humans is associated with liver dysfunction, mitochondrial myopathy, and CoQ decrease. To better understand the aetiology, we generated a heterozygous Adck2 knockout mouse. Adck2+/− mice exhibited impaired fatty acid oxidation, liver dysfunction, mitochondrial myopathy, and a decrease in CoQ in skeletal muscle.Since Adck2+/− mice show marked metabolic deregulation, we further studied their phenotype using caloric restriction (CR) as a metabolic chronic stressor by reducing by 40% the calory intake without malnutrition. CR increases healthspan and lifespan, and delays the onset of chronic diseases associated to aging.

Impaired spermatogenesis and male infertility are common manifestations of mitochondrial diseases, but the underlying mechanisms are unclear. Here we show that mice deficient for the mitochondrial intra-membrane rhomboid protease PARL, a recently reported model of Leigh syndrome, develop early testicular atrophy caused by a complete arrest of spermatogenesis at meiotic prophase I, followed by germ cell death independently of neurodegeneration. Genetic modifications of PINK1, PGAM5, and TTC19, three major substrates of PARL with important roles in mitochondrial homeostasis, do not reproduce or modify this severe phenotype. PARL deficiency in spermatocytes leads to severe abnormalities in mitochondrial structure associated with prominent electron transfer chain defects, alterations in Coenzyme Q (CoQ) biosynthesis, and metabolic rewiring. These mitochondrial defects are associated with a germ-cell specific decrease in GPX4 expression committing arrested spermatocytes to ferroptosis, a regulated cell death modality characterized by uncontrolled lipid peroxidation. Thus, mitochondrial defects, such as those induced by depletion of PARL, spontaneously initiate ferroptosis in primary spermatocytes in vivo by simultaneous effects on GPX4 and CoQ, the two major ferroptosis-inhibitors. Ferroptosis warrants to be further scrutinized in the pathogenesis of mitochondrial diseases and male infertility.

Aging and many of the chronic metabolic diseases related to aging show mitochondrial dysfunction. Accumulation of defective mitochondria is associated with the progression of the systemic deterioration associated with aging. Dysfunctional mitochondria create high levels of reactive oxygen species (ROS) that produce oxidative damage in cells and organs. Accumulation of damaged mitochondria contributes to a process in which dysfunctional mitochondria increase mtROS production that oxidizes molecules, mainly in the mitochondria, which increases the damage in mitochondria, creating even more ROS release. This vicious cycle can be blocked by increasing mitochondrial turnover through inducing mito/autophagy and mitochondrial biogenesis and/or by the treatment with CoQ10-related mitochondrial targeted antioxidants able to reduce oxidative damage.

Abstract BACKGROUND: SARS-CoV-2 infection is associated with inflammation, decrease in antioxidants and oxidative damage. We aimed to investigate whether ubiquinol, reduced form of coenzyme Q10 (CoQ10), with mountain spa rehabilitation (MR) will contribute to recovering of patients with post-COVID-19 syndrome. METHODS: The study included 36 patients on MR lasting 16-18 days. Twenty-two patients were supplemented with ubiquinol 2x100 mg/day (MRQ), 14 underwent MR without supplementation. The control group consisted of 15 healthy volunteers. Concentrations of total CoQ10 (ubiquinone+ ubiquinol), a-and?-tocopherol were determined in platelets (PLT), in blood and plasma, also ß-carotene was determined. Plasma concentration of thiobarbituric acid-reactive substances (TBARS) was used as the oxidative stress marker. Clinical symptoms were evaluated by questionnaire. RESULTS: MRQ …

Mitochondrial dysfunction is one of the main factors that affects aging progression and many age-related diseases. Accumulation of dysfunctional mitochondria can be driven by unbalanced mito/autophagy or by decrease in mitochondrial biosynthesis and turnover. Coenzyme Q is an essential component of the mitochondrial electron transport chain and a key factor in the protection of membrane and mitochondrial DNA against oxidation. Coenzyme Q levels decay during aging and this can be considered an accelerating factor in mitochondrial dysfunction and aging progression. Supplementation with coenzyme Q is successful for some tissues and organs but not for others. For this reason, the role of coenzyme Q in systemic aging is a complex picture that needs different strategies depending on the organ considered the main objective to be addressed. In this chapter we focus on the different effects of coenzyme Q and related compounds and the probable strategies to induce endogenous synthesis to maintain healthy aging.

Cardiovascular diseases are the leading cause of death globally and more than four out of five cases are due to ischemic events. Cardiac fibroblasts (CF) contribute to normal heart development and function, and produce the post‐ischemic scar. Here, we characterize the biochemical and functional aspects related to CF endurance to ischemia‐like conditions. Expression data mining showed that cultured human CF (HCF) express more BCL2 than pulmonary and dermal fibroblasts. In addition, gene set enrichment analysis showed overrepresentation of genes involved in the response to hypoxia and oxidative stress, respiration and Janus kinase (JAK)/Signal transducer and Activator of Transcription (STAT) signaling pathways in HCF. BCL2 sustained survival and proliferation of cultured rat CF, which also had higher respiration capacity and reactive oxygen species (ROS) production than pulmonary and dermal …

Coenzyme Q10 (CoQ10) is an essential factor for mitochondrial activity and antioxidant protection of cells, tissues and plasma lipoproteins. Its deficiency has been associated with aging progression in animals and humans. To determine if CoQ10 levels in plasma can be associated with frailty in elderly people (aged > 65), we studied the relationship of CoQ10 levels in blood with other parameters in plasma and with the physical activity and capacity in aged people. Our results indicate that high CoQ10 levels are directly associated with lower cardiovascular risk measured by the quotient total cholesterol/HDL cholesterol. Furthermore, high CoQ10 levels were found in people showing higher physical activity, stronger muscle capacity. CoQ10 also showed a strong inverse relationship with sedentarism and the up and go test, which is considered to be a frailty index. Interestingly, we found gender differences, indicating stronger correlations in women than in men. The importance of the maintenance of CoQ10 levels in elderly people to avoid sarcopenia and frailty in elderly people is discussed.

ObjectivesThe use of whole body-electrostimulation (WB-EMS) in combination with strength exercises has been proposed in order to improve muscle strength and rehabilitation. However, the combination of stimulation of muscle with exercise can induce muscle fibers break. This manuscript study Pilates Mat without or in combination with WB-EMS in trained individuals in order to determine the level of muscle damage.MethodsWe determined the effect of WB-EMS in combination of Pilates Mat in eighteen healthy and trained Intermediate Pilates Mat volunteers to determine the release of muscle damage biomarkers in plasma. Plasma levels of muscle damage markers (CK and transaminases) were determined by enzymatic assays.ResultsWe found that WB-EMS produced a high rise of the release of creatine kinase and transaminases in individuals whereas Pilates Mat did not produce such as effect. The levels of …

Coenzyme Q (CoQ) is a ubiquitous lipidic molecule located in all cell membranes and lipoproteins in blood plasma. Its phenolic head gives it the capacity to accept and donate electrons. For this reason, it is the main lipidic redox compound in cells. This property permits CoQ to take part in the mitochondrial electron transfer chain and in many other activities in mitochondria, and also to act as the major antioxidant in the lipid environment of the organism. During aging, the endogenous synthesis of CoQ decreases. Due to its central function, this decrease can affect many metabolic, signaling, and antioxidant activities, probably severely influencing aging progression. Further, CoQ depletion has been also associated with many aging-associated and metabolic diseases. This chapter revises the importance of this key molecule in cell physiology and aging progression.

European Association of Spa Rehabilitation recommend spa rehabilitation for patients with post COVID-19 syndrome (post C-19). We studied effects of special mountain spa rehabilitation program and its combination with ubiquinol (reduced form of coenzyme Q10 – CoQ10) supplementation on pulmonary function, clinical symptoms, endogenous CoQ10 levels, and platelet mitochondrial bioenergetics of patients with post C-19. 36 patients with post C-19 enrolled for rehabilitation in mountain spa resort and 15 healthy volunteers representing the control group were included in this study. 14 patients with post C-19 (MR group) were on mountain spa rehabilitation lasting 16 – 18 days, 22 patients (MRQ group) were supplemented with ubiquinol (2x100 mg/day) during the rehabilitation and additional 12–14 days at home. Clinical symptoms and functional capacity of the lungs were determined in patients before and after the spa rehabilitation program. Platelet bioenergetics by high-resolution respirometry, plasma TBARS concentration, and CoQ10 concentration in blood, plasma and platelets were evaluated before and after the spa rehabilitation program, and in 8 patients of MRQ group also after additional 12–14 days of CoQ10 supplementation. Pulmonary function and clinical symptoms improved after the rehabilitation program in both groups, 48.2 % of symptoms disappeared in the MR group and 62.8 % in the MRQ group. Platelet mitochondrial Complex I (CI)-linked oxidative phosphorylation (OXPHOS) and electron transfer (ET) capacity were markedly reduced in both groups of patients. After the rehabilitation program the improvement of these …

ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle …

ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle …

Coenzyme Q (CoQ) is a key component for many essential metabolic and antioxidant activities in cells in mitochondria and cell membranes. Mitochondrial dysfunction is one of the hallmarks of aging and age-related diseases. Deprivation of CoQ during aging can be the cause or the consequence of this mitochondrial dysfunction. In any case, it seems clear that aging-associated CoQ deprivation accelerates mitochondrial dysfunction in these diseases. Non-genetic prolongevity interventions, including CoQ dietary supplementation, can increase CoQ levels in mitochondria and cell membranes improving mitochondrial activity and delaying cell and tissue deterioration by oxidative damage. In this review, we discuss the importance of CoQ deprivation in aging and age-related diseases and the effect of prolongevity interventions on CoQ levels and synthesis and CoQ-dependent antioxidant activities.

Primary coenzyme Q10 (CoQ) deficiency includes a heterogeneous group of mitochondrial diseases characterized by low mitochondrial levels of CoQ due to decreased endogenous biosynthesis rate. These diseases respond to CoQ treatment mainly at the early stages of the disease. The advances in the next generation sequencing (NGS) as whole-exome sequencing (WES) and whole-genome sequencing (WGS) have increased the discoveries of mutations in either gene already described to participate in CoQ biosynthesis or new genes also involved in this pathway. However, these technologies usually provide many mutations in genes whose pathogenic effect must be validated. To functionally validate the impact of gene variations in the disease’s onset and progression, different cell models are commonly used. We review here the use of yeast strains for functional complementation of human genes, dermal skin fibroblasts from patients as an excellent tool to demonstrate the biochemical and genetic mechanisms of these diseases and the development of human-induced pluripotent stem cells (hiPSCs) and iPSC-derived organoids for the study of the pathogenesis and treatment approaches.

Coenzyme Q is a unique lipidic molecule highly conserved in evolution and essential to maintaining aerobic metabolism. It is endogenously synthesized in all cells by a very complex pathway involving a group of nuclear genes that share high homology among species. This pathway is tightly regulated at transcription and translation, but also by environment and energy requirements. Here, we review how coenzyme Q reacts within mitochondria to promote ATP synthesis and also integrates a plethora of metabolic pathways and regulates mitochondrial oxidative stress. Coenzyme Q is also located in all cellular membranes and plasma lipoproteins in which it exerts antioxidant function, and its reaction with different extramitochondrial oxidoreductases contributes to regulate the cellular redox homeostasis and cytosolic oxidative stress, providing a key factor in controlling various apoptosis mechanisms. Coenzyme Q levels can be decreased in humans by defects in the biosynthesis pathway or by mitochondrial or cytosolic dysfunctions, leading to a highly heterogeneous group of mitochondrial diseases included in the coenzyme Q deficiency syndrome. We also review the importance of coenzyme Q levels and its reactions involved in aging and age-associated metabolic disorders, and how the strategy of its supplementation has had benefits for combating these diseases and for physical performance in aging.

Coenzyme Q10 (CoQ10) deficiency is a rare disease characterized by a decreased accumulation of CoQ10 in cell membranes. Considering that CoQ10 synthesis and most of its functions are carried out in mitochondria, CoQ10 deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ10 deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ10 supplementation. Defects in components of the synthesis machinery caused by mutations in COQ genes generate the primary deficiency of CoQ10. Mutations in genes that are not directly related to the synthesis machinery cause secondary deficiency. Cases of CoQ10 deficiency without genetic origin are also considered a secondary deficiency. Both types of deficiency can lead to similar clinical manifestations, but the knowledge about primary deficiency is deeper than secondary. However …

Organisms maintain a complex relationship between the production of oxidative radicals and endogenous antioxidant levels and antioxidant enzymatic activities. Apart of its bioenergetics role in mitochondria, CoQ10 is also present in the rest of cell membranes and in plasma lipoproteins. In these structures, CoQ10 plays a key antioxidant role, preventing lipidic oxidative damage and regulating enzymatic and regulatory activities. Many years ago, two essential CoQ10-dependent dehydrogenases were characterized, cytochrome b5 reductase and NQO1. These enzymes are able to maintain a redox cycle of CoQ10 in membrane, preventing oxidative damage and maintaining other antioxidant systems depending on ascorbic acid and α-tocopherol. Recently, other CoQ10-dependent enzymes such as a mitochondrial dehydrogenase (FSP1) and a dehydrogenase associated with the outer leaf of the plasma …

Ubiquinol, the reduced form of Coenzyme Q 10 (CoQ 10), is a key factor in bioenergetics and antioxidant protection. During competition, professional soccer players suffer from considerable physical stress causing high risk of muscle damage. For athletes, supplementation with several antioxidants, including CoQ 10, is widely recommended to avoid oxidative stress and muscle damage. We performed an observational study of plasma parameters associated with CoQ 10 levels in professional soccer players of the Spanish First League team Athletic Club de Bilbao over two consecutive seasons (n= 24–25) in order determine their relationship with damage, stress and performance during competition. We analyzed three different moments of the competition: preterm, initial phase and mid phase. Metabolites and factors related with stress (testosterone/cortisol) and muscle damage (creatine kinase) were determined …

The decline of the immune system associated to aging is becoming a global issue nowadays due to the increase of lifespan. Immunosenescence is the deteriorated adaptative capacity of the immune system leading to increase in morbidity and mortality in elderly population. Aging has been related to a progressive affectation of mitochondria such as increase of mtDNA mutation, deregulation of electron transport chain, increase in ROS production and reduction in ATP production. Immunosenescence has been associated with aging associated mitochondrial dysfunction linked to chronic inflammation that induce higher oxidative stress levels and mitochondrial damage deteriorating the already compromised immune system. CoQ10 administration could be considered a beneficial strategy in order to reduce the progression of age-related diseases. Highlighting the important role of CoQ10 on mitochondrial …

Resveratrol (RSV) is a bioactive natural molecule that induces antioxidant activity and increases protection against oxidative damage. RSV could be used to mitigate damages associated to metabolic diseases and aging. Particularly, RSV regulates different aspects of mitochondrial metabolism. However, no information is available about the effects of RSV on Coenzyme Q (CoQ), a central component in the mitochondrial electron transport chain. Here, we report for the first time that RSV modulates COQ genes and parameters associated to metabolic syndrome in mice. Mice fed with high fat diet (HFD) presented a higher weight gain, triglycerides (TGs) and cholesterol levels while RSV reverted TGs to control level but not weight or cholesterol. HFD induced a decrease of COQs gene mRNA level, whereas RSV reversed this decrease in most of the COQs genes. However, RSV did not show effect on CoQ9, CoQ10 and total CoQ levels, neither in CoQ-dependent antioxidant enzymes. HFD influenced mitochondrial dynamics and mitophagy markers. RSV modulated the levels of PINK1 and PARKIN and their ratio, indicating modulation of mitophagy. In summary, we report that RSV influences some of the metabolic adaptations of HFD affecting mitochondrial physiology while also regulates COQs gene expression levels in a process that can be associated with mitochondrial dynamics and turnover.

Calorie restriction is the most effective intervention with prolongevity effects in many of the organisms. Calorie restriction can be considered as the reduction of the intake of energy without reaching malnutrition. The effect of calorie restriction is not only reserved to an extended longevity but also delays the onset and reduces the progression of age-related diseases. Caloric restriction-dependent activation of metabolic sensors such as AMPK and Sirtuins, the repression of mTOR and the activation of autophagy/mitophagy plays an essential role in its effect on health and longevity. Although the reduction of protein intake and amino acid restriction has been associated with the effect of calorie restriction, many studies indicate that is the reduction of calories the main factor in its prolongevity effect. In humans, calorie restriction has demonstrated their positive effect on the progression of many metabolic diseases associated with aging such as cardiovascular disease and type II diabetes. Regulation of the metabolism and the elimination of damaged structures, such as mitochondria, are essential to maintain an extended longevity and in the maintenance of health-span by preventing the onset and progression of age-related diseases.

Coenzyme Q10 (CoQ10) is an essential factor for aerobic bioenergetics and antioxidant protection in cell membranes and blood plasma lipoproteins. It is a component of the electron transport chain in mitochondria and the trans plasma membrane electron transport. Its deficiency in human causes CoQ10 deficiency syndrome, a heterogeneous group of mitochondrial diseases. Decrease of CoQ10 levels has been also associated with aging progression and age-related diseases. Human supplementation with CoQ10 has improved the progression of age-dependent diseases and decreased the mortality caused by these diseases. Some of them are linked to oxidative damage such as cardiovascular disease and fibrosis. However, its use as supplement depends on its bioavailability and in the capacity to reach organs and tissues. Other strategies to increase endogenous CoQ10 biosynthesis during aging would be …

SARS-CoV-2 causes a severe pneumonia (COVID-19) that affects essentially elderly people. In COVID-19, macrophage infiltration into the lung causes a rapid and intense cytokine storm leading finally to a multi-organ failure and death. Comorbidities such as metabolic syndrome, obesity, type 2 diabetes, lung and cardiovascular diseases, all of them age-associated diseases, increase the severity and lethality of COVID-19. Mitochondrial dysfunction is one of the hallmarks of aging and COVID-19 risk factors. Dysfunctional mitochondria is associated with defective immunological response to viral infections and chronic inflammation. This review discuss how mitochondrial dysfunction is associated with defective immune response in aging and different age-related diseases, and with many of the comorbidities associated with poor prognosis in the progression of COVID-19. We suggest here that chronic inflammation …

Something that we have learned from the pandemia caused by coronavirus isthat solutionsin healthrequire coordinated actions. Beside this and other (re)emerging infectious diseases, spain and europe are suffereng a plethora of disorders that are actually adquiring epidemic dimensions, including cancer, rare disesases, pain and food allergies between others. New tools for prevention, diagnosis and treatment need to be urgently designed and implemented using new holistic and multidisciplinary approaches that involve researchers, clinicials, industryand all stakeholthersof health system. CSIC is excellently positioned to lead and coordinate these challengesin Biomedicine and Health.

Non-alcoholic fatty liver disease (NAFLD) is a major health problem, and its prevalence has increased in recent years. Diet and exercise interventions are the first-line treatment options, with weight loss via a hypocaloric diet being the most important therapeutic target in NAFLD. However, most NAFLD patients are not able to achieve such weight loss. Therefore, the requisite is the investigation of other effective therapeutic approaches. This review summarizes research on understanding complex pathophysiology underlying dietary approaches and exercise interventions with the potential to prevent and treat NAFLD.

SNPs asociados con el endofenotipo nefritis lúpica pediátrica a partir del análisis de los datos completos del exoma. Un estudio piloto en pacientes colombianos | DIGITAL.CSIC Skip navigation Logo pequeño DigitalCISC Producción CSIC Áreas e Institutos Navegar ítems por: Fecha Publicación Autor Título Palabras Clave Autor con perfil Proyecto de investigación Grupo de investigación Agencia Financiadora Fecha Envío Pasarela Estadísticas Contacto Servicios Mi DIGITAL.CSIC Suscripciones Editar perfil 1.DIGITAL.CSIC 2.Biología y Biomedicina 3.Centro Andaluz de Biología del Desarrollo (CABD) 4.(CABD) Comunicaciones congresos Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/230438 COMPARTIR / EXPORTAR: logo share SHARE BASE Comparte tu historia de Acceso Abierto Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | …

Organisms maintain a complex relationship between the production of oxidative radicals and endogenous antioxidant levels and antioxidant enzymatic activities. Apart of its bioenergetics role in mitochondria, CoQ10 is also present in the rest of cell membranes and in plasma lipoproteins. In these structures, CoQ10 plays a key antioxidant role, preventing lipidic oxidative damage and regulating enzymatic and regulatory activities. Many years ago, two essential CoQ10-dependent dehydrogenases were characterized, cytochrome b5 reductase and NQO1. These enzymes are able to maintain a redox cycle of CoQ10 in membrane, preventing oxidative damage and maintaining other antioxidant systems depending on ascorbic acid and α-tocopherol. Recently, other CoQ10-dependent enzymes such as a mitochondrial dehydrogenase (FSP1) and a dehydrogenase associated with the outer leaf of the plasma membrane have increased the importance of CoQ10 in the prevention of oxidative damage and the regulation of apoptosis. The role of these enzymes in aging remains to be clearly determined but CR, a known prolongevity procedure, increases the activity of CoQ10-dependent dehydrogenases and prevents oxidative damage associated with aging. Then, maintenance of the activity of these extramitochondrial CoQ10-dependent activities seems to be important for aging and longevity.