Familial thrombotic microangiopathy in a child with coenzyme Q10 deficiency-associated glomerulopathy.

We report a child with biallelic COQ6 variants presenting with familial thrombotic microangiopathy (TMA). A Chinese boy presented with steroid-resistant nephrotic syndrome at 8 months old and went into kidney failure requiring peritoneal dialysis at 15 months old. He presented with hypertensive encephalopathy with the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute on chronic kidney injury at 25 months old following a viral illness. Kidney biopsy showed features of chronic TMA. He was managed with supportive therapy and plasma exchanges and maintained on eculizumab. However, he had another TMA relapse despite complement inhibition a year later. Eculizumab was withdrawn, and supportive therapies, including ubiquinol (50 mg/kg/day) and vitamins, were optimized. He remained relapse-free since then for 4 years. Of note, his elder sister succumbed to multiple organ failure with histological evidence of chronic TMA at the age of 4. Retrospective genetic analysis revealed the same compound heterozygous variants in the COQ6 gene.

Associations between Long-Term Dietary Coenzyme Q10 Intake and New-Onset Hypertension in Adults: Insights from a Nationwide Prospective Cohort Study.

Coenzyme Q10 (CoQ10) supplementation appears to be associated with a lower blood pressure. Nevertheless, it remains unclear whether food-sourced CoQ10 will affect new-onset hypertension in general adults. This study investigated the relationship between dietary CoQ10 intake and new-onset hypertension among the general population. Participants without hypertension at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort study were included (n = 11,428). Dietary CoQ10 intake was collected by validated dietary recalls and the food weighing method. Linear and non-linear relationships between dietary CoQ10 intake and new-onset hypertension were analyzed using multivariable Cox proportional hazards models and restricted cubic splines. During follow-up (median: 6 years), 4006 new-onset hypertension cases were documented. Compared with non-consumers, the hazard ratio (HR) and 95% confidence interval (CI) from quintile 2 to 4 total dietary CoQ10 were 0.83 (0.76, 0.91), 0.86 (0.78, 0.94) and 1.01 (0.92, 1.11); total plant-derived CoQ10 were 0.80 (0.73, 0.88), 1.00 (0.91, 1.09) and 1.10 (1.00, 1.20); and animal-derived CoQ10 were 0.65 (0.59, 0.71), 0.58 (0.53, 0.64) and 0.68 (0.62, 0.75). The lowest risk was found at moderate intake, with a non-linear relationship (P nonlinearity < 0.05). Furthermore, the overall inverse association was stronger among individuals without alcohol consumption or eating a low-fat diet. Moderate long-term dietary CoQ10 intake might be protective against new-onset hypertension. However, it follows a non-linear relationship and excessive intake may increase the risk of new-onset hypertension in the Chinese population.

Role of Dietary Antioxidant Supplements in Male Infertility: A Review.

Infertility, which affects around 70 million couples globally, is the inability to conceive after at least a year of continuous, unprotected sexual activity. Male-related elements are involving half of all infertility cases globally. Male infertility has various characteristics, including oligospermia, asthenozoospermia, and teratozoospermia. The purpose of this study was to assess the impact of antioxidant-rich food supplements on the properties of semen, like concentration of sperm, morphology, motility, fertility rate, and damage of DNA. Terms such as coenzyme Q10, antioxidants, folic acid, vitamin C, vitamin E, male infertility, selenium and others, were used to search for relevant research papers in the PubMed database. The findings of this study demonstrated beneficial improvements in semen parameters among infertile men who consumed dietary supplements, particularly combining antioxidants like coenzyme Q10, vitamin C, and vitamin E.

Gastroprotective and microbiome-modulating effects of ubiquinol in rats with radiation-induced enteropathy.

Radiation enteritis is a frequently encountered issue for patients receiving radiotherapy and has a significant impact on cancer patients' quality of life. The gut microbiota plays a pivotal role in intestinal function, yet the impact of irradiation on gut microorganisms is not fully understood. This study explores the gastroprotective effect and gut microbiome-modulating potential of ubiquinol (Ubq), the reduced form of the powerful antioxidant CoQ-10. For this purpose, male albino rats were randomly assigned to four groups: Control, IRR (acute 7 Gy γ-radiation), Ubq_Post (Ubq for 7 days post-irradiation), and Ubq_Pre/Post (Ubq for 7 days pre and 7 days post-irradiation). The fecal microbiomes of all groups were profiled by 16S rRNA amplicon sequencing followed by bioinformatics and statistical analysis. Histopathological examination of intestinal tissue indicated severe damage in the irradiated group, which was mitigated by ubiquinol with enhanced regeneration, goblet cells, and intestinal alkaline phosphatase expression. Compared to the irradiated group, the Ubq-treated groups had a significant recovery of intestinal interleukin-1ß, caspase-3, nitric oxide metabolites, and thio-barbituric reactive substances to near-healthy levels. Ubq_Pre/Post group displayed elevated peroxisome proliferator-activated receptor (PPAR-γ) level, suggesting heightened benefits. Serum insulin reduction in irradiated rats improved post-Ubq treatment, with a possible anti-inflammatory effect on the pancreatic tissue. Fecal microbiota profiling revealed a dysbiosis state with a reduction of bacterial diversity post-irradiation, which was re-modulated in the Ubq treated groups to profiles that are indistinguishable from the control group. These findings underscore Ubq's gastroprotective effects against radiation-induced enteritis and its potential in restoring the gut microbiota's diversity and balance.

Nrf2/FSP1/CoQ10 axis-mediated ferroptosis is involved in sodium aescinate-induced nephrotoxicity.

Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events, particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability, disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the -1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.

New variants expand the neurological phenotype of COQ7 deficiency.

The protein encoded by COQ7 is required for CoQ10 synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ10) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ10 deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ10 primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients. However, the specific combination of the identified variants in each patient generated precise pathophysiological and molecular alterations in fibroblasts, which would explain the differential in vitro response to supplementation therapy. Our results suggest that COQ7 dysfunction could be caused by specific structural changes that affect the interaction with COQ9 required for the DMQ10 presentation to COQ7, the substrate access to the active site, and the maintenance of the active site structure. Remarkably, patients' fibroblasts share transcriptional remodeling, supporting a modification of energy metabolism towards glycolysis, which could be an adaptive mechanism against CoQ10 deficiency. However, transcriptional analysis of mitochondria-associated pathways showed distinct and dramatic differences between patient fibroblasts, which correlated with the extent of pathophysiological and neurological alterations observed in the probands. Overall, this study suggests that the combination of precise genetic diagnostics and the availability of new structural models of human proteins could help explain the origin of phenotypic pleiotropy observed in some genetic diseases and the different responses to available therapies.

Coenzyme Q10 and Vitamin E Regulate the Bioactivity of Human Corneal Fibroblast Cells.

Purpose: Corneal fibroblasts are involved in the wound healing of the cornea with proliferation, migration, and differentiation processes. Coenzyme Q10 (CoQ10) and vitamin E can enhance corneal wound healing when applied after a corneal lesion as an eye drop. Thus, this study was performed to determine the potential efficiency of a CoQ10 ophthalmical solution containing a CoQ10 and vitamin E D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-derived formulation in human corneal fibroblasts (HCFs) in vitro. Methods: Primary HCFs were obtained from cadaveric corneal tissue, and cell viability was determined using MTT assay at 24 and 72 h. Cell migration was evaluated using an in vitro wound healing assay, and mRNA expressions of collagen type I (COL-I), collagen type III (COL-III), lumican, hyaluronan, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, tissue inhibitors of MMP (TIMP)-1, TIMP-2, interleukin (IL)-1ß, IL-6, IL-8, and IL-10 were assessed using reverse transcription polymerase chain reaction at 24 and 72 h. Results: At various concentrations of CoQ10 ophthalmical solution (CoQ10-os), cell viability and wound healing rates of HCFs increased compared with the control group. The expressions of COL-I, COL-III, lumican, and hyaluronan were increased by CoQ10-os, whereas those of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 were not affected by CoQ10-os at 24 and 72 h. In treating HCFs with a CoQ10-os medium, IL-1ß, IL-6, and IL-8 decreased, whereas IL-10 was significantly increased in a time- and dose-dependent manner. Conclusions: The findings indicate that CoQ10 and vitamin E-TPGS are potent regulators of the bioactivity of HCFs, thus supporting their potential application as ophthalmical solutions in therapies aimed at the fast regeneration of damaged cornea tissues.

Antioxidants and Fertility in Women with Ovarian Aging: A Systematic Review and Meta-Analysis.

Ovarian aging is a major factor for female subfertility. Multiple antioxidants have been applied in different clinical scenarios, but their effects on fertility in women with ovarian aging are still unclear. To address this, a meta-analysis was performed to evaluate the effectiveness and safety of antioxidants on fertility in women with ovarian aging. A total of 20 randomized clinical trials with 2617 participants were included. The results showed that use of antioxidants not only significantly increased the number of retrieved oocytes and high-quality embryo rates but also reduced the dose of gonadotropin, contributing to higher clinical pregnancy rates. According to the subgroup analysis of different dose settings, better effects were more pronounced with lower doses; in terms of antioxidant types, coenzyme Q10 (CoQ10) tended to be more effective than melatonin, myo-inositol, and vitamins. When compared with placebo or no treatment, CoQ10 showed more advantages, whereas small improvements were observed with other drugs. In addition, based on subgroup analysis of CoQ10, the optimal treatment regimen of CoQ10 for improving pregnancy rate was 30 mg/d for 3 mo before the controlled ovarian stimulation cycle, and women with diminished ovarian reserve clearly benefited from CoQ10 treatment, especially those aged <35 y. Our study suggests that antioxidant consumption is an effective and safe complementary therapy for women with ovarian aging. Appropriate antioxidant treatment should be offered at a low dose according to the patient's age and ovarian reserve. This study was registered at PROSPERO as CRD42022359529.

Evaluating the efficacy of ubiquinol in heart failure patients: a systematic review and meta-analysis.

Aim: We aim to analyze past literature to evaluate the efficacy of coenzyme Q10 (CoQ-10) in the population with heart failure (HF). Methods: A systematic literature search was conducted through MEDLINE (via PubMed) and Cochrane Library. The outcomes analyzed were a reduction in HF-related mortality, an improvement in exercise capacity, and the left ventricular ejection fraction (LVEF). Results: Among 16 studies, CoQ-10 significantly reduced HF-related mortality by 40% and improved exercise capacity in patients with HF, but demonstrated no significant difference in LVEF however, the potential of its efficacy on LVEF could not be ruled out. Conclusion: CoQ-10 significantly enhances exercise capacity and reduces HF-related mortality; however, its impact on patients with reduced LVEF requires further investigation.

[Box: see text].

Mini-encyclopedia of mitochondria-relevant nutraceuticals protecting health in primary and secondary care-clinically relevant 3PM innovation.

Despite their subordination in humans, to a great extent, mitochondria maintain their independent status but tightly cooperate with the "host" on protecting the joint life quality and minimizing health risks. Under oxidative stress conditions, healthy mitochondria promptly increase mitophagy level to remove damaged "fellows" rejuvenating the mitochondrial population and sending fragments of mtDNA as SOS signals to all systems in the human body. As long as metabolic pathways are under systemic control and well-concerted together, adaptive mechanisms become triggered increasing systemic protection, activating antioxidant defense and repair machinery. Contextually, all attributes of mitochondrial patho-/physiology are instrumental for predictive medical approach and cost-effective treatments tailored to individualized patient profiles in primary (to protect vulnerable individuals again the health-to-disease transition) and secondary (to protect affected individuals again disease progression) care. Nutraceuticals are naturally occurring bioactive compounds demonstrating health-promoting, illness-preventing, and other health-related benefits. Keeping in mind health-promoting properties of nutraceuticals along with their great therapeutic potential and safety profile, there is a permanently growing demand on the application of mitochondria-relevant nutraceuticals. Application of nutraceuticals is beneficial only if meeting needs at individual level. Therefore, health risk assessment and creation of individualized patient profiles are of pivotal importance followed by adapted nutraceutical sets meeting individual needs. Based on the scientific evidence available for mitochondria-relevant nutraceuticals, this article presents examples of frequent medical conditions, which require protective measures targeted on mitochondria as a holistic approach following advanced concepts of predictive, preventive, and personalized medicine (PPPM/3PM) in primary and secondary care.

The effect of coenzyme Q10 intake on metabolic profiles in women candidates for in-vitro fertilization: a randomised trial.

Objective: Infertility and the pathogenesis of polycystic ovarian syndrome (PCOS) are both influenced by insulin resistance and dyslipidemia. Presumably, adding coenzyme Q10 (CoQ10) to these patients' diets will be beneficial. Therefore, this study aimed to examine the effects of CoQ10 supplementation on metabolic profiles in women candidates for in-vitro fertilization (IVF). Trial design and methods: For this randomized, double-blinded, parallel, placebo-controlled clinical experiment, 40 PCOS-positive infertile women who were IVF candidates were included. They ranged in age from 18 to 40. The 20 participants in the two intervention groups received either CoQ10 or a placebo for 8 weeks. The expression of glucose transporter 1 (GLUT-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), low-density lipoprotein receptor (LDLR), as well as metabolic profiles such as insulin metabolism and lipid profiles were evaluated. Quantitative RT-PCR determined the expression of GLUT-1, PPAR-γ, and LDLR on peripheral blood mononuclear cells. Lipid profiles and fasting glucose were assessed using enzymatic kits, and insulin was determined using Elisa kit. Results: In comparison to the placebo, CoQ10 supplementation significantly reduced blood insulin levels (-0.3±1.0 vs. 0.5±0.7, P=0.01) and insulin resistance (-0.1±0.2 vs. 0.1±0.2, P=0.01), and increased PPAR-γ expression (P=0.01). In infertile PCOS patients' candidates for IVF, CoQ10 supplementation showed no appreciable impact on other metabolic profiles. Also, CoQ10 supplementation revealed no significant impact on GLUT-1 (P=0.30), or LDLR (P=0.27) expression. Within-group changes in insulin levels (P=0.01) and insulin resistance (P=0.01) showed a significant elevation in the placebo group. When we adjusted the analysis for baseline BMI, baseline values of variables, and age, our findings were not affected. Conclusions: Eight weeks of CoQ10 supplementation demonstrated positive benefits on PPAR-γ expression, insulin resistance, and serum insulin in infertile PCOS women candidates for IVF.

Evaluation of the protective effect of coenzyme Q10 on hepatotoxicity caused by acute phosphine poisoning.

Background: Aluminum phosphide (AlP) poisoning is prevalent in numerous countries, resulting in high mortality rates. Phosphine gas, the primary agent responsible for AlP poisoning, exerts detrimental effects on various organs, notably the heart, liver and kidneys. Numerous studies have documented the advantageous impact of Coenzyme Q10 (CoQ10) in mitigating hepatic injuries. The objective of this investigation is to explore the potential protective efficacy of CoQ10 against hepatic toxicity arising from AlP poisoning. Method: The study encompassed distinct groups receiving almond oil, normal saline, exclusive CoQ10 (at a dosage of 100 mg/kg), AlP at 12 mg/kg; LD50 (lethal dose for 50%), and four groups subjected to AlP along with CoQ10 administration (post-AlP gavage). CoQ10 was administered at 10, 50, and 100 mg/kg doses via Intraparietal (ip) injections. After 24 h, liver tissue specimens were scrutinized for mitochondrial complex activities, oxidative stress parameters, and apoptosis as well as biomarkers such as aspartate transaminase (AST) and alanine transaminase (ALT). Results: AlP induced a significant decrease in the activity of mitochondrial complexes I and IV, as well as a reduction in catalase activity, Ferric Reducing Antioxidant Power (FRAP), and Thiol levels. Additionally, AlP significantly elevated oxidative stress levels, indicated by elevated reactive oxygen species (ROS) production, and resulted in the increment of hepatic biomarkers such as AST and ALT. Administration of CoQ10 led to a substantial improvement in the aforementioned biochemical markers. Furthermore, phosphine exposure resulted in a significant reduction in viable hepatocytes and an increase in apoptosis. Co-treatment with CoQ10 exhibited a dose-dependent reversal of these observed alterations. Conclusion: CoQ10 preserved mitochondrial function, consequently mitigating oxidative damage. This preventive action impeded the progression of heart cells toward apoptosis.

Efficacy and Safety of Coenzyme Q10 Supplementation in Neonates, Infants and Children: An Overview.

To date, there have been no review articles specifically relating to the general efficacy and safety of coenzyme Q10 (CoQ10) supplementation in younger subjects. In this article, we therefore reviewed the efficacy and safety of CoQ10 supplementation in neonates (less than 1 month of age), infants (up to 1 year of age) and children (up to 12 years of age). As there is no rationale for the supplementation of CoQ10 in normal younger subjects (as there is in otherwise healthy older subjects), all of the articles in the medical literature reviewed in the present article therefore refer to the supplementation of CoQ10 in younger subjects with a variety of clinical disorders; these include primary CoQ10 deficiency, acyl CoA dehydrogenase deficiency, Duchenne muscular dystrophy, migraine, Down syndrome, ADHD, idiopathic cardiomyopathy and Friedreich's ataxia.

Use of coenzyme Q-10 to improve the pregnancy rate in sheep.

One of the factors responsible for less pregnancy rates is the use of frozen semen in sheep due to the oxidative stress created by the process. The aim of this experiment was to test the effects of adding coenzyme Q-10 (CoQ10) to the seminal extender on sperm quality and the pregnancy rate of sheep. In this study, ejaculates from eight Dorper rams of reproductive age were used and tested in four treatments: Control (pure BotuBov®), C1 (175 µM of CoQ10), C3 (350 µM of CoQ10), and C7 (700 µM of CoQ10). Samples were collected in triplicate from each animal, and sperm analysis was performed by CASA after thawing at 0 h and 2 h. The samples were also analyzed by flow cytometry for plasma and acrosomal membrane integrity, stability, lipid peroxidation, mitochondrial potential, and superoxide anion production. In total, 198 ewes were inseminated by laparoscopy and divided into two groups: control (n=98) and C7 (n=100). Pregnancy diagnosis was performed at 30 days. Coenzyme Q10 proved to be safe for semen cryopreservation, not altering sperm kinetic values between the groups post-thawing. In flow cytometry, the C1 and C7 groups achieved a better index of plasma membrane integrity and membrane stability (P<0.05). A increased pregnancy rate was observed in C7 (52 %) compared to the control (38 %). In conclusion, coenzyme Q10 assists in the cryopreservation process, protecting the sperm cell and improving pregnancy rates in ewes.

Effect of Coenzyme Q10 Supplementation on Vascular Endothelial Function: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Coenzyme Q10 (CoQ10) has gained attention as a potential therapeutic agent for improving endothelial function. Several randomized clinical trials have investigated CoQ10 supplementation's effect on endothelial function. However, these studies have yielded conflicting results, therefore this systematic review and meta-analysis were conducted. AIM: This systematic review and meta-analysis were conducted to assess the effects of CoQ10 supplementation on endothelial factors. METHODS: A comprehensive search was done in numerous databases until July 19th, 2023. Quantitative data synthesis was performed using a random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis, and publication bias. RESULTS: 12 studies comprising 489 subjects were included in the meta-analysis. The results demonstrated significant increases in Flow Mediated Dilation (FMD) after CoQ10 supplementation (WMD: 1.45; 95% CI: 0.55 to 2.36; p < 0.02), but there is no increase in Vascular cell adhesion protein (VCAM), and Intercellular adhesion molecule (ICAM) following Q10 supplementation (VCAM: SMD: - 0.34; 95% CI: - 0.74 to - 0.06; p < 0.10) (ICAM: SMD: - 0.18; 95% CI: - 0.82 to 0.46; p < 0.57). The sensitivity analysis showed that the effect size was robust in FMD and VCAM. In meta-regression, changes in FMD percent were associated with the dose of supplementation (slope: 0.01; 95% CI: 0.004 to 0.03; p = 0.006). CONCLUSIONS: CoQ10 supplementation has a positive effect on FMD in a dose-dependent manner. Our findings show that CoQ10 has an effect on FMD after 8 weeks of consumption. Additional research is warranted to establish the relationship between CoQ10 supplementation and endothelial function.

Neuron-targeted liposomal coenzyme Q10 attenuates neuronal ferroptosis after subarachnoid hemorrhage by activating the ferroptosis suppressor protein 1/coenzyme Q10 system.

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.

Coenzyme Q4 is a functional substitute for coenzyme Q10 and can be targeted to the mitochondria.

Coenzyme Q10 (CoQ10) is an important cofactor and antioxidant for numerous cellular processes, and its deficiency has been linked to human disorders including mitochondrial disease, heart failure, Parkinson's disease, and hypertension. Unfortunately, treatment with exogenous CoQ10 is often ineffective, likely due to its extreme hydrophobicity and high molecular weight. Here, we show that less hydrophobic CoQ species with shorter isoprenoid tails can serve as viable substitutes for CoQ10 in human cells. We demonstrate that CoQ4 can perform multiple functions of CoQ10 in CoQ-deficient cells at markedly lower treatment concentrations, motivating further investigation of CoQ4 as a supplement for CoQ10 deficiencies. In addition, we describe the synthesis and evaluation of an initial set of compounds designed to target CoQ4 selectively to mitochondria using triphenylphosphonium. Our results indicate that select versions of these compounds can successfully be delivered to mitochondria in a cell model and be cleaved to produce CoQ4, laying the groundwork for further development.

Mitochondrial Dysfunction due to Novel COQ8A Variation with Poor Response to CoQ10 Treatment: A Comprehensive Study and Review of Literatures.

COQ8A plays an important role in the biosynthesis of coenzyme Q10 (CoQ10), and variations in COQ8A gene are associated with primary CoQ10 deficiency-4 (COQ10D4), also known as COQ8A-ataxia. The current understanding of the association between the specific variant type, the severity of CoQ10 deficiency, and the degree of oxidative stress in individuals with primary CoQ10 deficiencies remains uncertain. Here we provide a comprehensive analysis of the clinical and genetic characteristics of an 18-year-old patient with COQ8A-ataxia, who exhibited novel compound heterozygous variants (c.1904_1906del and c.637C > T) in the COQ8A gene. These variants reduced the expression levels of COQ8A and mitochondrial proteins in the patient's muscle and skin fibroblast samples, contributed to mitochondrial respiration deficiency, increased ROS production and altered mitochondrial membrane potential. It is worth noting that the optimal treatment for COQ8A-ataxia remains uncertain. Presently, therapy consists of CoQ10 supplementation, however, it did not yield significant improvement in our patient's symptoms. Additionally, we reviewed the response of CoQ10 supplementation and evolution of patients in previous literatures in detail. We found that only half of patients could got notable improvement in ataxia. This research aims to expand the genotype-phenotype spectrum of COQ10D4, address discrepancies in previous reviews regarding the effectiveness of CoQ10 in these disorders, and help to establish a standardized treatment protocol for COQ8A-ataxia.

The role of CoQ10 in embryonic development.

Coenzyme Q10 (CoQ10) is a natural component widely present in the inner membrane of mitochondria. CoQ10 functions as a key cofactor for adenosine triphosphate (ATP) production and exhibits antioxidant properties in vivo. Mitochondria, as the energy supply center of cells, play a crucial role in germ cell maturation and embryonic development, a complicated process of cell division and cellular differentiation that transforms from a single cell (zygote) to a multicellular organism (fetus). Here, we discuss the effects of CoQ10 on oocyte maturation and the important role of CoQ10 in the growth of various organs during different stages of fetal development. These allowed us to gain a deeper understanding of the pathophysiology of embryonic development and the potential role of CoQ10 in improving fertility quality. They also provide a reference for further developing its application in clinical treatments.

Involvement of Nrf2-PPAR-γ signaling in Coenzyme Q10 protecting effect against methotrexate-induced testicular oxidative damage.

Studies have identified Coenzyme Q10 (CoQ10) as a promising agent in improving idiopathic male infertility; however, its role in chemically or environmentally induced testicular dysfunction is not well-established. We investigated the potential of CoQ10 to attenuate methotrexate (MTX)-induced testicular damage and to identify molecular targets of CoQ10 effects. Wistar rats received a single intraperitoneal dose of 20 mg/kg MTX on the fifth day of the 10-day experimental protocol. 100 mg/kg CoQ10 was given orally daily for ten days, alone or combined with MTX. The testes of MTX-treated animals showed thickened tunica albuginea, distortion of seminiferous tubules with a marked reduction of germinal lining, a few primary spermatocytes with no spermatozoa, apoptotic cells, congested sub-capsular and interstitial blood vessels, and interstitial edema. Reduction of reproductive hormones and increased oxidative, inflammatory, and apoptotic biomarkers levels were also seen in the MTX-treated rats. CoQ10 + MTX-treated rats were protected against MTX-induced testicular histological changes and showed improvement in testosterone, luteinizing-, and follicle-stimulating hormone serum levels compared to the MTX group. The testes of the CoQ10 + MTX-treated rats showed reduced malondialdehyde, myloperoxidase, tumor necrosis factor -α, interleukin-6 and -1ß and Bax: Bcl2 ratio and enhanced glutathione, and catalase compared to MTX alone. CoQ10 enhanced MTX-induced downregulation of Nrf2 and PPAR-γ signaling and modulated its downstream targets, the inducible nitric oxide synthase, NF-κB, Bax, and Bcl2. In conclusion, CoQ10 targeted the Nrf2-PPAR-γ signaling loop and its downstream pathways, mitigating MTX-induced oxidative stress-related damages and alleviating the testicular dysfunction MTX caused. Our data suggest Nrf2-PPAR-γ signaling as a potential therapeutic target in testicular toxicity, where oxidative stress, inflammation, and apoptosis trigger damage.