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Coenzyme Q10 (CoQ10) is necessary for mitochondrial electron transport. Mutations in CoQ10 biosynthetic genes cause primary CoQ10 deficiency (PCoQD) and manifest as mitochondrial disorders. It is often stated that PCoQD patients can be treated by oral CoQ10 supplementation. To test this, we compiled all studies describing PCoQD patients up to May 2022. We excluded studies with no data on CoQ10 treatment, or with insufficient description of effectiveness. Out of 303 PCoQD patients identified, we retained 89 cases, of which 24 reported improvements after CoQ10 treatment (27.0%). In five cases, the patient's condition was reported to deteriorate after halting of CoQ10 treatment. 12 cases reported improvement in the severity of ataxia and 5 cases in the severity of proteinuria. Only a subjective description of improvement was reported for 4 patients described as responding. All reported responses were partial improvements of only some symptoms. For PCoQD patients, CoQ10 supplementation is replacement therapy. Yet, there is only very weak evidence for the efficacy of the treatment. Our findings, thus, suggest a need for caution when seeking to justify the widespread use of CoQ10 for the treatment of any disease or as dietary supplement.

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.

With the appearance of new viruses and infectious diseases (ID) such as COVID-19 in 2019, as well as the lack of specific pharmacological tools for the management of patients with severe complications or comorbidities, it is important to search for adjuvant treatments that help improve the prognosis of infectious disease patients. It is also important that these treatments limit the oxidative and hyperinflammatory damage caused as a response to pathogenic agents, since, in some cases, an inflammatory syndrome may develop that worsens the patient’s prognosis. The potential benefits of complementary nutrients and dietary interventions in the treatment of pathological processes in which oxidative stress and inflammation play a fundamental role have been widely evaluated. Coenzyme Q10 (CoQ10) is a supplement that has been shown to protect cells and be effective in cardiovascular diseases and obesity. Additionally, some studies have proposed it as a possible adjuvant treatment in viral infections. Preclinical and clinical studies have shown that CoQ10 has anti-inflammatory and antioxidant effects, and effects on mitochondrial dysfunction, which have been linked to the inflammatory response.

Background Primary coenzyme Q10 (CoQ10) deficiencies are clinically and genetically heterogeneous group of disorders associated with defects of genes involved in the CoQ10 biosynthesis pathway. COQ7‐associated CoQ10 deficiency is very rare and only two cases have been reported. Methods and Results We report a patient with encephalo‐myo‐nephro‐cardiopathy, persistent lactic acidosis, and basal ganglia lesions resulting in early infantile death. Using whole exome sequencing, we identified compound heterozygous variants in the COQ7 gene consisting of a deletion insertion resulting in frameshift [c.599_600delinsTAATGCATC, p.(Lys200Ilefs*56)] and a missense substitution [c.319C>T, p.(Arg107Trp), NM_016138.4]. Skin fibroblast studies showed decreased combined complex II + III activity and reduction in CoQ10 level. Conclusion This third patient presenting with lethal encephalo‐myo‐nephro‐cardiopathy represents the severe end of this ultra‐rare mitochondrial disease caused by biallelic COQ7 mutations. The response to CoQ10 supplement is poor and alternative treatment strategies should be developed for a more effective management of this disorder.

Purpose: Schwannomatosis, a subtype of neurofibromatosis, is characterized by multiple benign, nonvestibular, nonintradermal schwannomas. Although the tumor suppressor SMARCB1 gene has been frequently identified as the underlying genetic cause of half of familial and ~10% of sporadic schwannomatosis, for most other cases, further causative genes remain to be discovered. Herein, we characterize the genome of a schwannomatosis family without constitutional inactivation of the SMARCB1 gene to explore novel genomic alterations predisposing individuals to the familial disease. Methods: We performed whole-genome/exome sequencing on genomic DNA of both schwannomatosis-affected and normal members of the family. Results: We identified a novel missense mutation (p.Asp208His; c.622G>C) in the coenzyme Q10 (CoQ10) biosynthesis monooxygenase 6 gene ( COQ6 ) in schwannomatosis-affected members. The deleterious effects of the COQ6 mutations were validated by their lack of complementation in a coq6 -deficient yeast mutant. Our study further indicated that the resultant haploinsufficiency of COQ6 might lead to CoQ10 deficiency and chronic overproduction of reactive oxygen species in Schwann cells. Conclusion: Although the exact oncogenetic mechanisms in this schwannomatosis family remain to be elucidated, our data strongly indicate a probable role of COQ6 mutation and CoQ10 deficiency in the development of familial schwannomatosis. Genet Med 16 10, 787–792.

Oxidative stress (OS) is a key contributing factor in 30–80% of male infertility cases. To date, several antioxidant treatments have been put forth to manage OS-induced male infertility. This study intended to elucidate the impact of coenzyme Q10 (CoQ10) and selenium on seminal fluid parameters and antioxidant status in infertile men with idiopathic oligoasthenoteratospermia (OAT). In this prospective study, 70 patients with idiopathic OAT were randomly allocated to receive CoQ10 (200 mg/day) or selenium (200 μg/day) for 3 months. Semen quality parameters (following WHO guidelines, 5th edition), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activities were compared before and after the treatment. The results of the study showed an increase in sperm concentration with CoQ10 treatment (p < 0.01) as well as increased progressive sperm motility (p < 0.01 and p < 0.05) and total sperm motility (p < 0.01 and p < 0.05) with CoQ10 and selenium treatment respectively. There was also a significant improvement in TAC (p < 0.01 and p < 0.05) and SOD (p < 0.01 and p < 0.05) following treatment with CoQ10 and selenium respectively while CAT improved only with CoQ10 therapy (p < 0.05). Sperm concentration, motility, and morphology also correlated significantly with TAC, SOD, and CAT (r = 0.37–0.76). In conclusion, treatment with CoQ10 (200 mg) or selenium (200 μg) could improve sperm concentration, motility, and antioxidant status in infertile men with idiopathic OAT with CoQ10 providing the higher improvement.

Ocular neurodegenerative diseases such as glaucoma, diabetic retinopathy, and age-related macular degeneration are common retinal diseases responsible for most of the blindness causes in the working-age and elderly populations in developed countries. Many of the current treatments used in these pathologies fail to stop or slow the progression of the disease. Therefore, other types of treatments with neuroprotective characteristics may be necessary to allow a more satisfactory management of the disease. Citicoline and coenzyme Q10 are molecules that have neuroprotective, antioxidant, and anti-inflammatory properties, and their use could have a beneficial effect in ocular neurodegenerative pathologies. This review provides a compilation, mainly from the last 10 years, of the main studies that have been published on the use of these drugs in these neurodegenerative diseases of the retina, analyzing the usefulness of these drugs in these pathologies.

In intensive duck production systems, vanadium (V) is widely used as a growth-promoting additive, but excessive supplementation poses health risks to ducks. Previous research indicated that V could cause damage to organs by disrupting the structure and function of mitochondria and the endoplasmic reticulum. However, the precise mechanism of mitochondrial-associated endoplasmic reticulum membranes (MAMs) in V-induced hepatotoxicity remains unclear. To fill this gap, this study employed network toxicology to analyze the hepatotoxicity of V, and further validated the pivotal roles of glucose homeostasis and ferroptosis in this process through targeted MAMs proteomics. The results indicated that V exposure increased liver dysfunction markers, disrupted hepatic cord structure, and widened ER-mitochondria gaps. Besides, V exposure up-regulated the levels of the IP3R-Grp75-VDAC1 complex in MAMs while promoting its dissociation. Moreover, the sequencing results of MAMs demonstrated that V primarily induced hepatotoxicity by disturbing the glycolysis/gluconeogenesis pathway. Notably, V exposure exacerbated lipid peroxides and Fe accumulation while inhibiting the NADH/FSP1/CoQ axis, down-regulating the expression levels of ferroptosis-related factors in livers. These findings demonstrated that dietary V overexposure impaired hepatic MAMs integrity, disrupted glucose homeostasis, and suppressed the NADH/FSP1/CoQ axis, which ultimately induced ferroptosis-mediated liver injury in ducks.

BackgroundMonoallelic variants in the KIF1A gene are associated with a large set of clinical phenotypes including neurodevelopmental and neurodegenerative disorders, underpinned by a broad spectrum of central and peripheral nervous system involvement.MethodsIn a multicenter study conducted in patients presenting spastic gait or complex neurodevelopmental disorders, we analyzed the clinical, genetic and neuroradiological features of 28 index cases harboring heterozygous variants in KIF1A. We conducted a literature systematic review with the aim to comparing our findings with previously reported KIF1A-related phenotypes.ResultsAmong 28 patients, we identified nine novel monoallelic variants, and one a copy number variation encompassing KIF1A. Mutations arose de novo in most patients and were prevalently located in the motor domain. Most patients presented features of a continuum ataxia-spasticity spectrum with only five cases showing a prevalently pure spastic phenotype and six presenting congenital ataxias. Seventeen mutations occurred in the motor domain of the Kinesin-1A protein, but location of mutation did not correlate with neurological and imaging presentations. When tested in 15 patients, muscle biopsy showed oxidative metabolism alterations (6 cases), impaired respiratory chain complexes II + III activity (3/6) and low CoQ10 levels (6/9). Ubiquinol supplementation (1gr/die) was used in 6 patients with subjective benefit.ConclusionsThis study broadened our clinical, genetic, and neuroimaging knowledge of KIF1A-related disorders. Although highly heterogeneous, it seems that manifestations of ataxia-spasticity spectrum disorders seem to occur in most patients. Some patients also present secondary impairment of oxidative metabolism; in this subset, ubiquinol supplementation therapy might be appropriate.