Mitochondrial Transport System Research Articles

Efficient Catalytic Conversion of Acetate to Citric Acid and Itaconic Acid by Engineered Yarrowia lipolytica

The bioconversion of agricultural and industrial wastes is considered a green and sustainable alternative method for producing high-value biochemicals. As a major catalytic product of greenhouse gases and a by-product in the fermentation and lignocellulose processing industries, acetate is a promising bioconversion raw material. In this work, endogenous and heterologous enzymes were manipulated in Yarrowia lipolytica to achieve the conversion of acetate to high-value citric acid and itaconic acid, respectively. After the combinational expression of the key enzymes in the acetate metabolic pathway, the citric acid synthesis pathway, and the mitochondrial transport system, acetate could be efficiently converted to citric acid. Coupled with the down-regulation of fatty acid synthase expression in the competitive pathway, more acetyl-CoA flowed into the synthesis of citric acid, and the titer reached 15.11 g/L with a productivity of 0.51 g/g acetate by the engineered Y. lipolytica, which is comparable to the results using glucose as the substrate. On this basis, the heterologous cis-aconitate decarboxylase from Aspergillus terreus was introduced into the engineered Y. lipolytica to achieve the catalytic synthesis of itaconic acid from acetate. Combined with investigating the effects of multiple enzymes in the synthesis pathway, the titer of itaconic acid reached 1.87 g/L with a yield of 0.43 g/g DCW by the final engineered strain, which is the highest reported titer of itaconic acid derived from acetate by engineered microbes in shake flasks. It is demonstrated that acetate has the potential to replace traditional starch-based raw materials for the synthesis of high-value organic acids and our work lays a foundation for the rational utilization of industrial wastes and the catalytic products of greenhouse gases.

Formulation Development and Evaluation of Ubidecarenone Chewable Tablet

Background: Coenzyme Q10 has a role in mitochondrial transport system and can be utilized as a supplement in migraine prevention. This study's objective is to assess Coenzyme Q10's effectiveness when used in conjunction with conventional medications to prevent migraines. Adding 300mg of coenzyme Q10 each day to prescription medications, while another group of patients continued receiving standard care. Over the course of a three-month treatment period, data on attack frequency, headache pain intensity, monthly migraine days, and associated symptoms like nausea, vomiting, phonophobia, and photophobia were analyses. Ubidecarenone, a medicinal component. The goal is to produce Ubidecarenone in a 300 mg chew-able tablet form. In vitro release studies and organoleptic properties, such as taste and flavour, will be evaluated. investigations in the early stages, tests for medicine excipient compatibility, and analyses of the water content Quality Assurance for the Process Hausner's Ratio, Bulk Density, Tapped Density, Comprehensibility Index, and Angle of Repose for calculating derived properties for medications and mixtures. ingredients that have been optimised for their concentrations, such as tastes, sweeteners, disintegrants, wetting agents, glidants, and lubricants. putting the best possible ingredients together to make a chew able pill. Evaluation of chewable tablets for post compression parameters including uniformity of weight, thickness, hardness, brittleness, friability, dissolution, assay, and in vitro drug release properties. An evaluation of the optimised batch's palatability is required. The intention is to create chewable tablets of ubidecarenone. Method: The wet granulation method is used to make chewable tablets of ubidecarenone. Mannitol is used as a diluent, crospovidone as a disintegrant agent, sodium starch as a disintegrate agent, saccharin sodium as a sucrose sweetener, orange flavour, peppermint oil as a flouring agent, and colloidal silicon dioxide as a gliding. The Ubidecarenone (300 mg) is one of the best first-line treatments for migraine prevention.

The Effect of Virgin Coconut Oil (VCO) on Malondialdehyde, Glutathione Peroxidase, and Cortisol Hormone Levels

Vigorous physical activity is a physical movement that produces excessive free radicals due to leakage of electrons from the mitochondrial transport system. The body's antioxidant system is reduced due to the inability of the body's defenses to reduce the production of free radicals resulting in oxidative stress, so it requires a supply of antioxidants from outside the body such as Virgin Coconut Oil (VCO). The purpose of this study is to determine the effect of VCO administration on malondialdehyde levels, glutathione peroxidase levels and cortisol hormone levels in male Wistar rats subjected to strenuous physical activity. The research method uses an experimental with posttest only control group design. The experimental subjects were 24 male Wistar rats which were randomly divided into 4 groups (K1, K2, K3, and K4). The administration of VCO at dose of 25 mL and 50 mL are based of human weight 70 kg and the conversion dose in mice (BB = 200 g) resulted in 0.45 mL/200 g BW/day and 0.9 mL/200 g BW / day which is made into a 1 mL solution and given orally for 28 days. K3 and K4 groups were given strenuous physical activity and given VCO at a dose of 0.45 and 0.9 mL/200 g BW/day. The measurement of malondialdehyde levels using the TBARS method. The glutathione peroxidase (GPx) and the cortisol hormone using ELISA method at PSPG UGM in June 2022. The lowest average levels of MDA and GPx were in the K1 group. One-Way Anova test result showed that the levels of malondialdehyde, glutathione peroxidase, and the cortisol hormone in the K3 and K4 groups had significant differences with K2 group (p < 0.05). The administration of VCO at doses of 0.45 mL/200 g BW/day and 0.9 mL/200 g BW/day could affect the levels of malondialdehyde, glutathione peroxidase, and the hormone cortisol in male Wistar rats subjected to strenuous physical activity.

TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy.

Ion fluxes across the inner mitochondrial membrane control mitochondrial volume, energy production, and apoptosis. TMBIM5, a highly conserved protein with homology to putative pH-dependent ion channels, is involved in the maintenance of mitochondrial cristae architecture, ATP production, and apoptosis. Here, we demonstrate that overexpressed TMBIM5 can mediate mitochondrial calcium uptake. Under steady-state conditions, loss of TMBIM5 results in increased potassium and reduced proton levels in the mitochondrial matrix caused by attenuated exchange of these ions. To identify the in vivo consequences of TMBIM5 dysfunction, we generated mice carrying a mutation in the channel pore. These mutant mice display increased embryonic or perinatal lethality and a skeletal myopathy which strongly correlates with tissue-specific disruption of cristae architecture, early opening of the mitochondrial permeability transition pore, reduced calcium uptake capability, and mitochondrial swelling. Our results demonstrate that TMBIM5 is an essential and important part of the mitochondrial ion transport system machinery with particular importance for embryonic development and muscle function.

Targeting mitochondrial protein transport system: a promising treatment strategy for heart failure?

Targeting mitochondrial protein transport system: a promising treatment strategy for heart failure?

Engineering Yarrowia lipolytica for the selective and high-level production of isocitric acid through manipulation of mitochondrial dicarboxylate–tricarboxylate carriers

During cultivation under nitrogen starvation, Yarrowia lipolytica produces a mixture of citric acid and isocitric acid whose ratio is mainly determined by the carbon source used. We report that mitochondrial succinate–fumarate carrier YlSfc1 controls isocitric acid efflux from mitochondria. YlSfc1 purified and reconstituted into liposomes transports succinate, fumarate, oxaloacetate, isocitrate and α-ketoglutarate. YlSFC1 overexpression determined the inversion of isocitric acid/citric acid ratio towards isocitric acid, resulting in 33.4 ± 1.9 g/L and 43.3 ± 2.8 g/L of ICA production in test-tube cultivation with glucose and glycerol, respectively. These titers represent a 4.0 and 6.3-fold increase compared to the wild type. YlSFC1 gene expression was repressed in the wild type strain grown in glucose-based medium compared to olive oil medium explaining the reason for the preferred citric acid production during Y. lipolytica growth on carbohydrates. Coexpression of YlSFC1 and adenosine monophosphate deaminase YlAMPD genes together with inactivation of citrate mitochondrial carrier YlYHM2 gene enhanced isocitric acid accumulation up to 41.4 ± 4.1 g/L with an isocitric acid/citric acid ratio of 14.3 in a small-scale cultivation with glucose as a carbon source. During large-scale cultivation with glucose pulse-feeding, the engineered strain produced 136.7 ± 2.5 g/L of ICA with a process selectivity of 88.1%, the highest reported titer and selectivity to date. These results represent the first reported isocitric acid secretion by Y. lipolytica as a main organic acid during cultivation on carbohydrate. Moreover, we demonstrate for the first time that the replacement of one mitochondrial transport system for another can be an efficient tool for switching product accumulation.

Regulation of Cell Death by Mitochondrial Transport Systems of Calcium and Bcl-2 Proteins.

Mitochondria represent the fundamental system for cellular energy metabolism, by not only supplying energy in the form of ATP, but also by affecting physiology and cell death via the regulation of calcium homeostasis and the activity of Bcl-2 proteins. A lot of research has recently been devoted to understanding the interplay between Bcl-2 proteins, the regulation of these interactions within the cell, and how these interactions lead to the changes in calcium homeostasis. However, the role of Bcl-2 proteins in the mediation of mitochondrial calcium homeostasis, and therefore the induction of cell death pathways, remain underestimated and are still not well understood. In this review, we first summarize our knowledge about calcium transport systems in mitochondria, which, when miss-regulated, can induce necrosis. We continue by reviewing and analyzing the functions of Bcl-2 proteins in apoptosis. Finally, we link these two regulatory mechanisms together, exploring the interactions between the mitochondrial Ca2+ transport systems and Bcl-2 proteins, both capable of inducing cell death, with the potential to determine the cell death pathway—either the apoptotic or the necrotic one.

WHY SOME YARROWIA LIPOLYTICA STRAINS SECRET CITRIC ACID TO THE MEDIUM?

Despite many studies, the “check points” of metabolic regulation of citric acid (CA) secretion by the yeasts Y.lipolytica still remain unknown. In this manuscript, some possible aspects of strain dependent secretion as well as CA metabolism regulation were discussed. Keys enzymes’ activities, substrate concentration, affinity of the uptake systems, intracellular CA concentration and strains abilities were the main points taken into consideration. The direction for the future studies emerged from this review, mainly connected to cellular and mitochondrial citrate transport systems and cellular substrates transporters (glucose, fructose, glycerol, ethanol and acetate), give promising starting point for future efficient strain development.

Diabetes Mellitus, Mitochondrial Dysfunction and Ca2+-Dependent Permeability Transition Pore

Diabetes mellitus is one of the most common metabolic diseases in the developed world, and is associated either with the impaired secretion of insulin or with the resistance of cells to the actions of this hormone (type I and type II diabetes, respectively). In both cases, a common pathological change is an increase in blood glucose—hyperglycemia, which eventually can lead to serious damage to the organs and tissues of the organism. Mitochondria are one of the main targets of diabetes at the intracellular level. This review is dedicated to the analysis of recent data regarding the role of mitochondrial dysfunction in the development of diabetes mellitus. Specific areas of focus include the involvement of mitochondrial calcium transport systems and a pathophysiological phenomenon called the permeability transition pore in the pathogenesis of diabetes mellitus. The important contribution of these systems and their potential relevance as therapeutic targets in the pathology are discussed.

Mitochondrial Citrate Transport System in the Fungus Mucor circinelloides: Identification, Phylogenetic Analysis, and Expression Profiling During Growth and Lipid Accumulation.

The mitochondrial citrate transport system, composed of citrate and malate transporters (MTs), can regulate the citrate efflux from mitochondria to cytosol, and then citrate is cleaved into OAA and acetyl-CoA which can be used for fatty acid (FA) biosynthesis. However, in the fungus Mucor circinelloides the molecular mechanism of citrate efflux from the mitochondria by this system and its role in FA synthesis is unclear. In the present study, we have analyzed the genome of high lipid-producing strain WJ11 and the low lipid-producing strain CBS 277.49 to find the potential genes involving in this system. Five potential genes are present in the genome of WJ11. These genes encode one citrate transport protein (CT), one tricarboxylate carrier (TCT), one MT, and two 2-oxoglutarate:malate antiporters (SoDIT-a and SoDIT-b). However, the genome of CBS 277.49 contains the same set of genes, except for the presence of just one SoDIT. The proteins from WJ11 had similar properties as their counterparts in CBS 277.49. Moreover, phylogenetic analyses revealed the evolutionary relationship of these proteins and illuminated their typical motifs related to potential functions. Additionally, the expression of these genes was analyzed to predict the possible functions in lipid metabolism in M. circinelloides. This is the first study to report the in silico analysis of structures and functions of the mitochondrial citrate transport system in M. circinelloides. This work showed a new strategy for research for the selection of candidate genes for further detailed functional investigation of the mitochondrial citrate transport system in lipid accumulation.

Targeting SLC25A10 alleviates improved antioxidant capacity and associated radioresistance of cancer cells induced by chronic-cycling hypoxia

High tumor heterogeneity and increased therapy resistance acquired in a hypoxic tumor microenvironment remain major obstacles to successful radiotherapy. Others and we have shown that adaptation of cancer cells to cycling severe hypoxia and intermittent reoxygenation stress (chronic-cycling hypoxia) increases cellular antioxidant capacity thereby supporting resistance to chemotherapy and radiotherapy. Here we explored the involvement of antioxidant-associated mitochondrial transport-systems for maintenance of redox-homeostasis in adaptation to chronic-cycling hypoxia and associated radioresistance.Genetic or pharmacological inhibition of the mitochondrial dicarboxylate carrier (SLC25A10) or the oxoglutarate-carrier (SLC25A11) increased the cytotoxic effects of ionizing radiation (IR). But only targeting of SLC25A10 was effective in overcoming chronic-cycling hypoxia-induced enhanced death resistance in vitro and in vivo by disturbing increased antioxidant capacity. Furthermore, in silico analysis revealed that overexpression of SLC25A10 but not SLC25A11 is associated with reduced overall survival in lung- and breast-cancer patients.Our study reveals a role of SLC25A10 in supporting both, redox- and energy-homeostasis, ensuring radioresistance of cancer cells with tolerance to chronic-cycling hypoxia thereby proposing a novel strategy to overcome a mechanism of hypoxia-induced therapy resistance with potential clinical relevance regarding decreased patient survival.

Mitochondrial Fatty Acid Transport System and its Relevance to Ovarian Function

Mitochondrial fatty acid oxidation is integral to folliculogenesis and oocyte maturation. Mitochondrial fatty acid transport system includes molecules such as 3-hydroxy-4-trimethylamino butyrate or carnitine, organic cation transporter novel 2 (OCTN2), carnitine palmitoyl transferase (CPT1), CPT2, and carnitine-acylcarnitine translocase (CACT). These are essential molecules that play an important role in the transport of activated long chain fatty acids from cytosol to the mitochondrial matrix where these subsequently undergo beta-oxidation. It has been well established that fatty acid metabolism is vital for follicles and oocyte growth. This review highlights the possible role of mitochondrial fatty transport acid system in ovarian function.

Mitochondrial network responses in oxidative physiology and disease.

Mitochondrial activities are linked directly or indirectly to all cellular functions in aerobic eukaryotes. Omics methods enable new approaches to study functional organization of mitochondria and their adaptive and maladaptive network responses to bioenergetic fuels, physiologic demands, environmental challenges and aging. In this review, we consider mitochondria collectively within a multicellular organism as a macroscale “mitochondriome”, functioning to organize bioenergetics and metabolism as an organism utilizes environmental resources and protects against environmental threats. We address complexities of knowledgebase-driven functional mapping of mitochondrial systems and then consider data-driven network mapping using omics methods. Transcriptome-metabolome-wide association study (TMWAS) shows connectivity and organization of nuclear transcription with mitochondrial transport systems in cellular responses to mitochondria-mediated toxicity. Integration of redox and respiratory measures with TMWAS shows central redox hubs separating systems linked to oxygen consumption rate and H2O2 production. Combined redox proteomics, metabolomics and transcriptomics further shows that physiologic network structures can be visualized separately from toxicologic networks. These data-driven integrated omics methods create new opportunities for mitochondrial systems biology.

Mitochondrial Translocase of the Outer Membrane Alterations May Underlie Dysfunctional Oxidative Phosphorylation in Alzheimer's Disease.

The translocase of the outer membrane (TOM) is a vital mitochondrial transport system facilitating the importation of nuclear encoded proteins into the organelle. While mitochondrial dysfunction, including perturbation of oxidative phosphorylation (OXPHOS) complex, is evident in Alzheimer's disease (AD), it remains unclear whether the observed OXPHOS deficits may be associated with TOM alterations. To correlate TOM subunits with OXPHOS complex proteins in AD. Postmortem neocortex (BA40) from AD and age-matched controls were processed to obtain mitochondrial enriched homogenates for the measurement of Tom20, Tom22, Tom40, and Tom70 as well as components of OXPHOS complex I-V by immunoblotting. Tom20 and Tom70 immunoreactivities were significantly reduced in AD, as were components of OXPHOS complex I and III. Both Tom20 and Tom70 positively correlated with complex III and V, while Tom20 also correlated withcomplex IV. Reductions in certain TOM subunits and their correlations with specific OXPHOS complex proteins suggest that an impaired mitochondrial transportation system may contribute to previously observed oxidative phosphorylation deficits in AD. Follow-up studies are needed to corroborate the present correlative study.

Origin and Evolutionary Alteration of the Mitochondrial Import System in Eukaryotic Lineages.

Protein transport systems are fundamentally important for maintaining mitochondrial function. Nevertheless, mitochondrial protein translocases such as the kinetoplastid ATOM complex have recently been shown to vary in eukaryotic lineages. Various evolutionary hypotheses have been formulated to explain this diversity. To resolve any contradiction, estimating the primitive state and clarifying changes from that state are necessary. Here, we present more likely primitive models of mitochondrial translocases, specifically the translocase of the outer membrane (TOM) and translocase of the inner membrane (TIM) complexes, using scrutinized phylogenetic profiles. We then analyzed the translocases’ evolution in eukaryotic lineages. Based on those results, we propose a novel evolutionary scenario for diversification of the mitochondrial transport system. Our results indicate that presequence transport machinery was mostly established in the last eukaryotic common ancestor, and that primitive translocases already had a pathway for transporting presequence-containing proteins. Moreover, secondary changes including convergent and migrational gains of a presequence receptor in TOM and TIM complexes, respectively, likely resulted from constrained evolution. The nature of a targeting signal can constrain alteration to the protein transport complex.

IFPA meeting 2015 workshop report I: placental mitochondrial function, transport systems and epigenetics

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops covered areas of placental regulation and nutrient handling: 1) placental epigenetics; 2) placental mitochondrial function; 3) placental transport systems.

Impaired transport of mitochondrial transcription factor A (TFAM) and the metabolic memory phenomenon associated with the progression of diabetic retinopathy

Diabetes damages retinal mitochondrial DNA (mtDNA) and compromises the mtDNA transcription. In the transcription and replication of mtDNA, nuclear-encoded mitochondrial transcription factor A (TFAM) is considered a key activator. We have shown that in diabetes, although retinal TFAM gene expression is increased, its mitochondrial levels are decreased. This study investigates the role of mitochondrial outer and inner membrane transport systems in the transfer of TFAM into the mitochondria in diabetes and how reversal of hyperglycaemia affects the ability of TFAM to reach the mitochondria. Components of the membrane transport system, Tom70, Tom40, Tim23, and Tim44, were analysed in the retina from streptozotocin-induced diabetic rats maintained in poor control or in good control for 8 months, or in poor control for 4 months followed by in good control for 4 months. The binding of TFAM with Tom70 and Tim44 was determined by co-immunoprecipitation and that with mtDNA by chromatin immunoprecipitation. Retinal expressions of Tom70, Tom40, and Tim44 were significantly decreased in diabetes, and the binding of TFAM with Tom70, Tim44, and mtDNA was impaired. Reversal of hyperglycaemia had no beneficial effect on the decreased binding of TFAM to Tom proteins and mtDNA. Thus, subnormal membrane transport to systems in diabetes impair the transfer of TFAM into the mitochondria, and decreased TFAM-mtDNA binding that results in subnormal mitochondria transcription. These processes continue to be dysfunctional even after the hyperglycaemic insult is terminated. Strategies targeting mitochondrial membrane transport proteins could have the potential of improving mitochondrial biogenesis and slowing or halting the progression of diabetic retinopathy.

Impact of phosphine exposure on development in Caenorhabditis elegans: Involvement of oxidative stress and the role of glutathione

Phosphine (PH3) is a widely used and ideal fumigant employed to control insect pests in stored grains and other commodities. Chemically, PH3 is a strong reducing agent and mainly affects the mitochondrial transport system in insects. PH3 toxicity to insects is also associated with oxidative imbalances. Besides inducing mortality, PH3 is shown to delay hatching and adversely affect fecundity/fertility of several stored product insect pests. Recent studies have demonstrated the utility of Caenorhabditis elegans as a model organism to obtain basic insights on the toxic implications of PH3. In the present study, we have examined the impact of PH3 on the development of C. elegans and the involvement of glutathione (GSH) in its developmental toxicity. We exposed eggs of C. elegans to two concentrations of PH3 (0.04 and 0.06mg/L) either in the presence or absence of a GSH depleting agent, diethyl maleate (DEM, 5mM) for 72h. PH3 exposure caused significant delay in the post embryonic development among worms as characterized by the inability of hatched worms to attain gravid adult stage by the end of 72h. Interestingly, among worms co-exposed to DEM+PH3, the decrease in GSH levels was associated with more pronounced developmental delay compared to that of worms exposed to PH3per se. Concomitantly, PH3-induced depletion of glutathione was associated with significant alterations in activities of key antioxidant enzymes. Our data demonstrate the vital role of GSH and antioxidant defenses among worms developing under PH3 exposure. Interestingly, this finding also unfolds newer possibilities for developing strategies to disrupt antioxidant defenses in insect pests to enhance the efficacy of PH3 treatment for the control of stored product insects.

Effect of methanol on mitochondrial organization in zebrafish (Danio rerio) ovarian follicles

Successful cryopreservation is usually measured in terms of cell survival. However, there may also be more subtle effects within cells that survive. Previous studies on zebrafish have produced evidence of mitochondrial DNA (mtDNA) damage in cryopreserved embryonic blastomeres and, after exposure to cryoprotectants, alterations in mtDNA replication in embryos and decreased mitochondrial membrane potential, mtDNA and ATP production in ovarian follicles. This study shows that the decreased ATP levels previously observed in stage III zebrafish ovarian follicles exposed to ≥3 M methanol persisted in those follicles that subsequently developed to stage IV. However, the decreased mtDNA levels were restored in those follicles. In order to determine whether mitochondrial distribution and/or their transport network was affected by the methanol exposure, immunocytochemistry analysis of tubulin and mitochondrial cytochrome c oxidase I (COX-I) was performed, along with phalloidin staining of polymerized actin. Neat arrangements of all proteins were observed in control follicles, with COX-I and tubulin being colocalized near granulosa cell nuclei, while actin formed hexagonal and/or polygonal structures nearer granulosa cell membranes and projected into the oocyte surface. Exposure to methanol (2 to 4 M) disrupted the COX-I and tubulin arrangements and the hexagonal and/or polygonal actin distribution and actin projections into the oocyte. These effects were still observed in those follicles that developed to stage IV, although the severity was reduced. In summary, the disruption to function and distribution of mitochondria in ovarian follicles exposed to > 2 M methanol may be mediated via disruption of the mitochondrial transport system. Some recovery of this disruption may take place after methanol removal and subsequent follicle maturation.

Is there is Need for Ubiquinone (CoQ10) Supplementation in Statin- Associated Myopathy?

Statins are currently the most effective drugs in reducing low-density lipoprotein cholesterol (LDL-C). With their mechanism of action, by inhibiting 3-hydroxy-3 methylglutharyl coenzyme A reductase, statins decrease cholesterol production. The same biosynthetic pathway is shared by ubiquinone or coenzyme Q10. Statins block production of dekaprenyl-4-benzoate, a precursor of coenzyme Q10 (CoQ10), which is an essential component in mitochondrial transport system. Ubiquinone deficiency may affect oxidative phosphorylation and adenosine triphosphate production, which can subsequently result in impairing of muscle energy metabolism and contribute to development of myopathy. Statin therapy also decreases antioxidant status in the body, resulting in to increase in free radical damage to cells in various parts of body; liver, nerves, muscles. Statins can decrease natural antioxidant protection present in our body and predispose toxicity. Statin-associated myopathy is the most common side effect of statin treatment often lead to statin dose reduction, or therapy cessation, which can negatively affect cardiovascular risk management. The spectrum of statin-related myopathy ranges from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. Observational studies suggest that myalgia can occur in up to 10% of persons prescribed statins, whereas rhabdomyolysis continues to be rare. Statins lower circulating levels of CoQ10 up to 54%, whereas several studies did not confirmed a lowering of CoQ10 levels in muscles during statin therapy and the evidence was given also on low dose of statin therapy, which did not appear to reduce intramuscular levels of CoQ10 in symptomatic patients with statin myopathy. The conflicting results have been published on the impaired mitochondrial function, which was found during the analysis of the myocyte cells in patients treated with statins. The supplementation of CoQ10 results in increasing of serum CoQ10, but it is not clear if it relieves myopatic symptoms in statin treated patients. Yet available intervention studies reported contrasting results and just two of them proved benefit of CoQ10 supplementation. Hence coenzyme Q10 supplementation is not currently recommended for routine use in the prophylaxis of statin toxicity.