Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival.

BACKGROUND: Pancreatic cancer is a leading cause of cancer-related deaths. Increased activity of the epidermal growth factor receptor (EGFR) is often observed in pancreatic cancer, and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration. Nevertheless, erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes. We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential (Δψm), facilitate tumor cell uptake of Δψm-sensitive agents, disrupt mitochondrial homeostasis, and subsequently trigger tumor cell death. Erlotinib has not been tested for this effect. AIM: To determine whether erlotinib can elevate Δψm and increase tumor cell uptake of Δψm-sensitive agents, subsequently triggering tumor cell death. METHODS: Δψm-sensitive fluorescent dye was used to determine how erlotinib affects Δψm in pancreatic adenocarcinoma (PDAC) cell lines. The viability of conventional and patient-derived primary PDAC cell lines in 2D- and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone (MitoQ), a Δψm-sensitive MitoQ. The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0. The preclinical efficacy of the two-drug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts. RESULTS: Erlotinib elevated Δψm in PDAC cells, facilitating tumor cell uptake and mitochondrial enrichment of Δψm-sensitive agents. MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses, while erlotinib pretreatment potentiated low doses of MitoQ. SynergyFinder suggested that these drugs synergistically induced tumor cell lethality. Consistent with in vitro data, erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent. CONCLUSION: Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.

Coenzyme Q10 in atherosclerosis.

Atherosclerotic disease is a chronic disease that predominantly affects the elderly and is the most common cause of cardiovascular death worldwide. Atherosclerosis is closely related to processes such as abnormal lipid transport and metabolism, impaired endothelial function, inflammation, and oxidative stress. Coenzyme Q10 (CoQ10) is a key component of complex Ⅰ in the electron transport chain and an important endogenous antioxidant that may play a role in decelerating the progression of atherosclerosis. Here, the different forms of CoQ10 presence in the electron transport chain are reviewed, as well as its physiological role in regulating processes such as oxidative stress, inflammatory response, lipid metabolism and cellular autophagy. It was also found that CoQ10 plays beneficial effects in atherosclerosis by mitigating lipid transportation, endothelial inflammation, metabolic abnormalities, and thrombotic processes from the perspectives of molecular mechanisms, animal experiments, and clinical evidence. Besides, the combined use of CoQ10 with other drugs has better synergistic therapeutic effects. It seems reasonable to suggest that CoQ10 could be used in the treatment of atherosclerotic cardiovascular diseases while more basic and clinical studies are needed.

The in vitro and in vivo depigmentation activity of coenzyme Q0, a major quinone derivative from Antrodia camphorata, through autophagy induction in human melanocytes and keratinocytes.

BACKGROUND: Coenzyme Q0 (CoQ0), a novel quinone derivative of Antrodia camphorata, has been utilized as a therapeutic agent (including antioxidant, anti-inflammatory, antiangiogenic, antiatherosclerotic, and anticancer agents); however, its depigmenting efficiency has yet to be studied. METHODS: We resolved the depigmenting efficiency of CoQ0 through autophagy induction in melanoma (B16F10) and melanin-feeding keratinocyte (HaCaT) cells and in vivo Zebrafish model. Then, MPLC/HPLC analysis, MTT assay, Western blotting, immunofluorescence staining, LC3 transfection, melanin formation, GFP-LC3 puncta, AVO formation, tyrosinase activity, and TEM were used. RESULTS: CoQ0-induced autophagy in B16F10 cells was shown by enhanced LC3-II accumulation, ATG7 expression, autophagosome GFP-LC3 puncta, and AVOs formation, and ATG4B downregulation, and Beclin-1/Bcl-2 dysregulation. In α-MSH-stimulated B16F10 cells, CoQ0 induced antimelanogenesis by suppressing CREB-MITF pathway, tyrosinase expression/activity, and melanin formation via autophagy. TEM data disclosed that CoQ0 increased melanosome-engulfing autophagosomes and autolysosomes in α-MSH-stimulated B16F10 cells. CoQ0-inhibited melanogenesis in α-MSH-stimulated B16F10 cells was reversed by pretreatment with the autophagy inhibitor 3-MA or silencing of LC3. Additionally, CoQ0-induced autophagy in HaCaT cells was revealed by enhanced LC3-II accumulation, autophagosome GFP-LC3 puncta and AVO formation, ATG4B downregulation, ATG5/ATG7 expression, and Beclin-1/Bcl-2 dysregulation. In melanin-feeding HaCaT cells, CoQ0 induced melanin degradation by suppressing melanosome gp100 and melanin formation via autophagy. TEM confirmed that CoQ0 increased melanosome-engulfing autophagosomes and autolysosomes in melanin-feeding HaCaT cells. Treatment with 3-MA reversed CoQ0-mediated melanin degradation in melanin-feeding HaCaT cells. In vivo study showed that CoQ0 suppressed endogenous body pigmentation by antimelanogenesis and melanin degradation through autophagy induction in a zebrafish model. CONCLUSIONS: Our results showed that CoQ0 exerted antimelanogenesis and melanin degradation by inducing autophagy. CoQ0 could be used in skin-whitening formulations as a topical cosmetic application.

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.

Comparison of Protective Effect of Tri-circulator and Coenzyme Q10 on Myocardial Injury and the Mechanism Study by Zebrafish Model.

Tri-Circulator (TC) is a product comprising coenzyme Q10 (CoQ10), Salvia miltiorrhiza, and Panax notoginseng. Individually, each of these constituents has demonstrated protective effects on myocardial injury. The purpose of this study is to evaluate the protective efficacy of TC on heart function and compare the differential effects between CoQ10 and TC. Two myocardial injury models of zebrafish, the hypoxia-reoxygenation model (H/R) and the isoproterenol (ISO, a ß-receptor agonist) model, were used in this experiment. The zebrafish subjects were divided into 4 groups: control, H/R, TC, and CoQ10. Heart rate, stroke volume (SV), cardiac output (CO), ejection fraction (EF), fractional area change (FAC), and pericardial height were monitored to assess changes in heart function. The gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was studied as markers of injury/stress. TC significantly suppresses elevated heart rate induced by H/R and prevents the decrease of heart rate induced by ISO. It alleviates the pericardial infusion induced by ISO, whereas CoQ10 does not possess a similar effect. Both TC and CoQ10 significantly inhibit the decline in SV, CO, EF, and FAC induced by H/R and ISO, and suppress the expression of ANP and BNP in cardiomyocytes induced by ISO. It is noteworthy that TC demonstrates a more pronounced effect on EF, FAC, ANP, and BNP gene expression compared to CoQ10. Both TC and CoQ10 have a protective effect on myocardial injury of zebrafish. However, TC exhibits a greater efficacy compared to CoQ10 alone in mitigating myocardial injury.

Selenium reduction of ubiquinone via SQOR suppresses ferroptosis.

The canonical biological function of selenium is in the production of selenocysteine residues of selenoproteins, and this forms the basis for its role as an essential antioxidant and cytoprotective micronutrient. Here we demonstrate that, via its metabolic intermediate hydrogen selenide, selenium reduces ubiquinone in the mitochondria through catalysis by sulfide quinone oxidoreductase. Through this mechanism, selenium rapidly protects against lipid peroxidation and ferroptosis in a timescale that precedes selenoprotein production, doing so even when selenoprotein production has been eliminated. Our findings identify a regulatory mechanism against ferroptosis that implicates sulfide quinone oxidoreductase and expands our understanding of selenium in biology.

Coenzyme Q10 improves the quality and in vitro fertility of post-thawed buffalo (Bubalus bubalis) semen via its antioxidative effect.

This study aimed to determine the effects of Coenzyme Q10 (CoQ10) in the freezing medium on functional and oxidative stress parameters and in vitro fertilization (IVF) rate of buffalo sperm. Collected samples were relocated to the laboratory for initial evaluation, gentle dilution in extenders, cooling (4°C, 2 h), equilibration (4°C, 4 h), packaging (straws, 0.5 mL), programmable freezing, and thawing (37°C, 30 s). Statistical analysis depicted that adding CoQ10 (100 µM) in a freezing medium caused a significant augmentation in total motility (%), average path, and straight-line velocities (µm/sec) of buffalo sperm than control. Adding CoQ10 (100 µM) improved sperm progressive motility, rapid velocity, and functional parameters (%) compared to the control and 10 µM of CoQ10. Moreover, CoQ10 in a freezing medium caused a significant augmentation in seminal plasma catalase (U/mL) and glutathione reductase (GSH; nmol/109 ) at 100 µM than control and other treatments. CoQ10 inclusion (100 µM) ameliorates seminal plasma superoxide dismutase (U/mL), glutathione-S-transferase (GST; nmol/mL/min) fructose (µg/mL), and ATP (nmol/million) than control. Furthermore, CoQ10 at 100 µM improved seminal plasma glutathione peroxidase (µM) levels than control, 10 µM, and 20 µM. Lastly, hydrogen peroxide (H2 O2; nM) production was significantly lower at 100 µM than at control and 10 µM. CoQ10 (100 µM) caused a significant augmentation in the un-capacitated pattern followed by a reduction in the capacitated pattern, and apoptosis-like changes (%) than control, and other treatments, whereas viability was increased than control and other treatments. CoQ10 (100 µM) significantly improved the IVF rate in comparison with control, CoQ10 at 10 µM, and 20 µM groups. In conclusion, the addition of CoQ10 (100 µM) in the freezing medium can improve the quality and in vitro fertility of post-thawed buffalo semen via its antioxidative effect. Further studies are needed to evaluate the effect of CoQ10 on the in vivo fertility of buffalo bull semen.

Brown adipose tissue CoQ deficiency activates the integrated stress response and FGF21-dependent mitohormesis.

Coenzyme Q (CoQ) is essential for mitochondrial respiration and required for thermogenic activity in brown adipose tissues (BAT). CoQ deficiency leads to a wide range of pathological manifestations, but mechanistic consequences of CoQ deficiency in specific tissues, such as BAT, remain poorly understood. Here, we show that pharmacological or genetic CoQ deficiency in BAT leads to stress signals causing accumulation of cytosolic mitochondrial RNAs and activation of the eIF2α kinase PKR, resulting in activation of the integrated stress response (ISR) with suppression of UCP1 but induction of FGF21 expression. Strikingly, despite diminished UCP1 levels, BAT CoQ deficiency displays increased whole-body metabolic rates at room temperature and thermoneutrality resulting in decreased weight gain on high-fat diets (HFD). In line with enhanced metabolic rates, BAT and inguinal white adipose tissue (iWAT) interorgan crosstalk caused increased browning of iWAT in BAT-specific CoQ deficient animals. This mitohormesis-like effect depends on the ATF4-FGF21 axis and BAT-secreted FGF21, revealing an unexpected role for CoQ in the modulation of whole-body energy expenditure with wide-ranging implications for primary and secondary CoQ deficiencies.

Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy.

Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% of patients, but we can neither predict nor understand the non-responders. Idebenone is reduced by the cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons to respiratory complex III, bypassing complex I affected in LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous. This hampers idebenone reduction. In its oxidized form, idebenone inhibits complex I, decreasing respiratory function in cells. By retrospectively analyzing a large cohort of idebenone-treated LHON patients, classified by their response to therapy, we show that patients with homozygous or compound heterozygous NQO1 variants have the poorest therapy response, particularly if carrying the m.3460G>A/MT-ND1 LHON mutation. These results suggest consideration of patient NQO1 genotype and mitochondrial DNA mutation in the context of idebenone therapy.

Ameliorating impact of coenzyme Q10 on the profile of adipokines, cardiomyopathy, and hematological markers correlated with the glucotoxicity sequelae in diabetic rats.

BACKGROUND: In diabetes, high blood glucose induces glucotoxicity, resulting in the further damage of pancreatic beta-cells and then precipitating diabetic complications. This study was aimed to investigate the relationship between glucotoxicity with the level of adipokines, diabetic cardiomyopathy, and hematological markers. Moreover, the study examined the potential modulatory effect of coenzyme Q10 (CoQ10) on the aforementioned markers associated with the sequelae of diabetes mellitus. MATERIAL AND METHODS: Twenty-four male rats were randomly assigned to receive an injection of STZ to induce diabetes (n = 16) or to remain uninduced (n = 8). The hyperglycemic status was induced in fasting rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer (pH 4.5). Three days after STZ injection, rats were divided into three groups; Normal control group (A), Diabetic control group (B), and CoQ10- treated diabetic group (C). The group (C) was fed with the basal diet supplemented with 5 g of CoQ10 per kilogram of diet for three weeks after the diabetes induction. After 21 days, the blood and serum samples were taken to conduct biochemical analyses. Blood glucose was determined by Blood Glucose Monitoring System. Adipokines or cytokines were evaluated by ELISA from a serum sample. Cardiac myopathy biomarkers were estimated by UP-Converting Phosphor Immunoassay Analyzer, and hematological parameters were measured by automatic hematology analyzer. RESULTS: In hyperglycemic rats, the level of fasting blood glucose, and serum level of resistin, omentin, TNF-α, and cardiomyopathy biomarkers significantly increased (P < 0.05). The treatment with CoQ10 significantly decreased the profile of adipokines and cardiomyopathy markers (cardiac enzymes and LPPLA2) in diabetic rats and also reduced glucose levels (P < 0.05). Lymphocyte percentages significantly decreased while significant increases were observed in granulocytes and MID percentages in hyperglycemic rats. CONCLUSION: Diabetic rats had higher serum levels of adipokines and cardiomyopathy markers. Among the hematological markers, GRA% and MID% increased while LYM% decreased. The profile of adipokines and cardiomyopathy markers improved when CoQ10 was supplemented. The study suggests that CoQ10 may have a beneficial effect on improving diabetic complications.

Coenzyme Q10 attenuates neurodegeneration in the cerebellum induced by chronic exposure to tramadol.

BACKGROUND: Chronic use of tramadol can cause neurotoxic effects and subsequently cause neurodegeneration in the cerebellum. The main damage mechanisms identified are oxidative stress and inflammation. Currently, we investigated the effects of coenzyme Q10 (CoQ10) in attenuates of neurodegeneration in the cerebellum induced by chronic exposure to tramadol. MATERIAL AND METHODS: Seventy-two male mature albino rats were allocated into four equal groups, including; non-treated group, CoQ10 group (which received CoQ10 at 200 mg/kg/day orally for three weeks), tramadol group (which received tramadol hydrochloride at 50 mg/kg/day orally for three weeks), and tramadol+CoQ10 group (which received tramadol and CoQ10 at the same doses as the previous groups). Tissue samples were obtained for stereological, immunohistochemical, biochemical, and molecular evaluations. Also, functional tests were performed to evaluate behavioral properties. RESULTS: We found a significant increase in stereological parameters, antioxidant factors (catalase, glutathione, and superoxide dismutase), and behavioral function scores in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). In addition, malondialdehyde levels, the density of apoptotic cells, as well as the expression of pro-inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6) and autophagy (lysosome-associated membrane protein 2, autophagy-related 5, beclin 1, and autophagy-related 12) genes were considerably reduced in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). CONCLUSION: We conclude that the administration of CoQ10 has neuroprotective effects in the cerebellum of rats that have chronic exposure to tramadol.

Trolox aids coenzyme Q10 in neuroprotection against NMDA induced damage via upregulation of VEGF in rat model of glutamate excitotoxicity.

Glutamate induced damage to retinal ganglion cells (RGCs) requires tight physiological regulation of the N-methyl-D-aspartate (NMDA) receptors. Previously, studies have demonstrated the neuroprotective abilities of antioxidants like coenzyme Q10 (CoQ10) and vitamin E analogs like α-tocopherol against neuropathies resulting from NMDA insult, but have failed to shed light on the effect of CoQ10 and trolox, a hydrophilic analog of vitamin E, on glaucomatous neurodegeneration. In the current study, we wanted to investigate whether the combined effect of trolox with CoQ10 could alleviate NMDA-induced death of retinal cells while also trying to elucidate the underlying mechanism in relation to the yet unexplained role of vascular endothelial growth factor (VEGF) in NMDA-mediated excitotoxicity. After successful NMDA-induced degeneration, we followed it up with the treatment of combination of Trolox and CoQ10. The structural damage by NMDA was repaired significantly and retina retained structural integrity comparable to levels of control in the treatment group of Trolox and CoQ10. Detection of ROS generation after NMDA insult showed that together, Trolox and CoQ10 could significantly bring down the high levels of free radicals while also rescuing mitochondrial membrane potential (MMP). A significant increase in NMDA receptor Grin2A by CoQ10 alone as well as by CoQ10 and trolox was accompanied by a lowered Grin2B receptor expression, suggesting neuroprotective action of Trolox and CoQ10. Subsequently, lowered VEGFR1 and VEGFR2 receptor expression by NMDA treatment also recovered when subjected to combined treatment of Trolox and CoQ10. Western blot analyses also indicated the same whereby Trolox and CoQ10 could increase the diminished levels of phosphorylated VEGFR2. Immunofluorescence studies also indicated a positive correlation between recovered VEGFR2 and NMDAR2A levels and diminished levels of NMDAR2D, confirming the results obtained by RT-PCR analysis. This is the first report in our knowledge that demonstrates the efficacy of trolox in combination with CoQ10 highlighting the importance of maintaining VEGF levels that are lowered in ocular diseases due to NMDA-related toxicities.

COQ10 PROVIDES CARDIOPROTECTION AGAINST THE TOXIC EFFECTS OF TRASTUZUMAB AND DOXORUBICIN IN RAT MODEL.

The study was aimed at investigating the effect of coenzyme Q10 (CoQ10) on reducing the cardiotoxic effects of trastuzumab (TRZ) and doxorubicin (DOX) in a rat model. The experiment duration was 20 days and involved sixteen healthy albino rats, subdivided into four groups: the negative control group, in which rats received a daily dose of a placebo vehicle; the positive control group, receiving a daily placebo vehicle and a single dose of a combination of TRZ+DOX; the third group, pretreated with CoQ10 (10 mg/kg orally daily for 10 days), followed by 10 days of placebo vehicle and a single dose of a combination of TRZ+DOX at day 10; and finally, the fourth group pretreated with 10 days of placebo vehicle then followed by CoQ10 (10 mg/kg orally daily for 10 days) and a single dose of a combination of TRZ+DOX at day 10. Histological analysis of cardiac tissues was conducted, and the serum levels of cardiac troponin and redox markers were evaluated. The results showed that there were several histopathological changes like necrosis, edema, inflammation, and others in Group 2, which did not receive CoQ10, with high serum levels of cTnI. However, a high degree of improvement was achieved in Groups 3 and 4 in which rats were administered CoQ10 either before or after TRZ and DOX administration. The improvement was expressed by the disappearance of histopathological changes and a significant decrease in the serum level of cardiac troponin compared with Group 2. The findings of the study suggest that the administration of CoQ10 could be beneficial in minimizing the cardiac side effects caused by TRZ and DOX. This study provides a basis for further research and development of CoQ10 as a potential cardioprotective agent against the cardiac side effects of chemotherapy.

Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene.

Recent findings have shown that fatty acid metabolism is profoundly involved in ferroptosis. However, the role of cholesterol in this process remains incompletely understood. In this work, we show that modulating cholesterol levels changes vulnerability of cells to ferroptosis. Cholesterol alters metabolic flux of the mevalonate pathway by promoting Squalene Epoxidase (SQLE) degradation, a rate limiting step in cholesterol biosynthesis, thereby increasing both CoQ10 and squalene levels. Importantly, whereas inactivation of Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), the branch point of cholesterol biosynthesis pathway, exhibits minimal effect on ferroptosis, simultaneous inhibition of both CoQ10 and squalene biosynthesis completely abrogates the effect of cholesterol. Mouse models of ischemia-reperfusion and doxorubicin induced hepatoxicity confirm the protective role of cholesterol in ferroptosis. Our study elucidates a potential role of ferroptosis in diseases related to dysregulation of cholesterol metabolism and suggests a possible therapeutic target that involves ferroptotic cell death.

Comparison of Coenzyme Q10 (Ubiquinone) and Reduced Coenzyme Q10 (Ubiquinol) as Supplement to Prevent Cardiovascular Disease and Reduce Cardiovascular Mortality.

PURPOSE OF REVIEW: According to the World Health Organization (WHO), cardiovascular disease is the leading cause of death worldwide. Heart failure has been defined as a global pandemic leading to millions of deaths. Recent research clearly approved the beneficial effect of Coenzyme Q10 supplementation in treatment and prevention of cardiovascular disease in patients with heart failure in clinical trials but did not distinguish between the oxidised form CoQ10 and reduced form CoQH2 of Coenzyme Q10. The aim of this study is to determine differences in medical application of CoQ10 and CoQH2 supplementation and evaluate the efficacy of CoQ10 and CoQH2 supplementation to prevent cardiovascular disease in patients with heart failure. RECENT FINDINGS: A PubMed search for the terms "ubiquinone" and "ubiquinol" was conducted, and 28 clinical trials were included. Our findings go along with the biochemical description of CoQ10 and CoQH2, recording cardiovascular benefits for CoQ10 and antioxidative and anti-inflammatory properties for CoQH2. Our main outcomes are the following: (I) CoQ10 supplementation reduced cardiovascular death in patients with heart failure. This is not reported for CoQH2. (II) Test concentrations leading to cardiovascular benefits are much lower in CoQ10 studies than in CoQH2 studies. (III) Positive long-term effects reducing cardiovascular mortality are only observed in CoQ10 studies. Based on the existing literature, the authors recommend CoQ10 instead of CoQH2 to treat and prevent cardiovascular disease in patients with heart failure.

Inhibition of Cronobacter sakazakii Biofilm Formation and Expression of Virulence Factors by Coenzyme Q0.

In this study, we investigated the inhibitory effects of coenzyme Q0 (CoQ0) on biofilm formation and the expression of virulence genes by Cronobacter sakazakii. We found that the minimum inhibitory concentration of CoQ0 against C. sakazakii strains ATCC29544 and ATCC29004 was 100 µg/mL, while growth curve assays showed that subinhibitory concentrations (SICs) of CoQ0 for both strains were 6.4, 3.2, 1.6 and 0.8 µg/mL. Assays exploring the inhibition of specific biofilm formation showed that SICs of CoQ0 inhibited biofilm formation by C. sakazakii in a dose-dependent manner, which was confirmed by scanning electron microscopy and confocal laser scanning microscopy analyses. CoQ0 inhibited the swimming and swarming motility of C. sakazakii and reduced its ability to adhere to and invade HT-29 cells. In addition, CoQ0 impeded the ability of C. sakazakii to survive and replicate within RAW 264.7 cells. Finally, real-time polymerase chain reaction analysis confirmed that nine C. sakazakii genes associated with biofilm formation and virulence were downregulated in response to CoQ0 treatment. Overall, our findings suggest that CoQ0 is a promising antibiofilm agent and provide new insights for the prevention and control of infections caused by C. sakazakii.

Lipid nanoparticles containing coenzyme Q10 for topical applications: An overview of their characterization.

The coenzyme Q10 is a compound widely used in pharmaceutical and cosmetic formulations because it is a potent eliminator of free radicals, giving it antioxidant and anti-aging properties. It is naturally synthesized by the human body, but its production wanes with age, leading to the formation of wrinkles. The efficacy of topical application of the coenzyme to counteract this process is subject to several difficulties, due to its instability in the presence of light, low solubility in water and high lipophilicity. Because of these drawbacks, many studies have been conducted of release systems. Lipid nanoparticles stand out in this sense due to the advantages of skin compatibility, protection of the active ingredient against degradation in the external medium, capacity to increase penetration of that ingredient in the skin, and its controlled and prolonged release. In this context, this article presents a review of the main studies of the coenzyme Q10 encapsulated in lipid nanoparticles for topical use, focusing on the analytic methods used to characterize the systems regarding morphology, zeta potential, release profile, Q10 content, encapsulation efficiency, crystalline organization and structure of the lipid matrix, rheology, antioxidant activity, skin penetration and efficacy, among other aspects. We also describe the main results of the different studies and discuss the critical aspects - the simplest, most reproducible, best, and most relevant - that characterize lipid nanoparticles with encapsulated Q10 for topical use.

Coenzyme Q-related compounds to maintain healthy mitochondria during aging.

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.

Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by Coenzyme Q.

Pathogenic variants in SPART cause Troyer syndrome, characterized by lower extremity spasticity and weakness, short stature and cognitive impairment, and a severe mitochondrial impairment. Herein, we report the identification of a role of Spartin in nuclear-encoded mitochondrial proteins. SPART biallelic missense variants were detected in a 5-year-old boy with short stature, developmental delay and muscle weakness with impaired walking distance. Patient-derived fibroblasts showed an altered mitochondrial network, decreased mitochondrial respiration, increased mitochondrial reactive oxygen species and altered Ca2+ versus control cells. We investigated the mitochondrial import of nuclear-encoded proteins in these fibroblasts and in another cell model carrying a SPART loss-of-function mutation. In both cell models the mitochondrial import was impaired, leading to a significant decrease in different proteins, including two key enzymes involved in CoQ10 (CoQ) synthesis, COQ7 and COQ9, with a severe reduction in CoQ content, versus control cells. CoQ supplementation restored cellular ATP levels to the same extent shown by the re-expression of wild-type SPART, suggesting CoQ treatment as a promising therapeutic approach for patients carrying mutations in SPART.