Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extramitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid, pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. In view of the central role of CoQ10 in cellular metabolism, it is unsurprising that a CoQ10 deficiency is linked to the pathogenesis of a range of disorders. CoQ10 deficiency is broadly classified into primary or secondary deficiencies. Primary deficiencies result from genetic defects in the multi-step biochemical pathway of CoQ10 synthesis, whereas secondary deficiencies can occur as result of other diseases or certain pharmacotherapies. In this article we have reviewed the clinical consequences of primary and secondary CoQ10 deficiencies, as well as providing some examples of the successful use of CoQ10 supplementation in the treatment of disease.

Mitochondrial dysfunction and oxidative stress have been implicated in the pathogenesis of a number of diseases and conditions. Oxidative stress occurs once the antioxidant defenses of the body become overwhelmed and are no longer able to detoxify reactive oxygen species (ROS). The ROS can then go unchallenged and are able to cause oxidative damage to cellular lipids, DNA and proteins, which will eventually result in cellular and organ dysfunction. Although not always the primary cause of disease, mitochondrial dysfunction as a secondary consequence disease of pathophysiology can result in increased ROS generation together with an impairment in cellular energy status. Mitochondrial dysfunction may result from either free radical-induced oxidative damage or direct impairment by the toxic metabolites which accumulate in certain metabolic diseases. In view of the importance of cellular antioxidant status, a number of therapeutic strategies have been employed in disorders associated with oxidative stress with a view to neutralising the ROS and reactive nitrogen species implicated in disease pathophysiology. Although successful in some cases, these adjunct therapies have yet to be incorporated into the clinical management of patients. The purpose of this review is to highlight the emerging evidence of oxidative stress, secondary mitochondrial dysfunction and antioxidant treatment efficacy in metabolic and non-metabolic diseases in which there is a current interest in these parameters.

Coenzyme Q10 (CoQ10) has a number of important roles in the cell that are required for optimal functioning of the immune system. These include its essential role as an electron carrier in the mitochondrial respiratory chain, enabling the process of oxidative phosphorylation to occur with the concomitant production of ATP, together with its role as a potential lipid-soluble antioxidant, protecting the cell against free radical-induced oxidation. Furthermore, CoQ10 has also been reported to have an anti-inflammatory role via its ability to repress inflammatory gene expression. Recently, CoQ10 has also been reported to play an important function within the lysosome, an organelle central to the immune response. In view of the differing roles CoQ10 plays in the immune system, together with the reported ability of CoQ10 supplementation to improve the functioning of this system, the aim of this article is to review the current literature available on both the role of CoQ10 in human immune function and the effect of CoQ10 supplementation on this system.

Coenzyme Q₁₀ (CoQ₁₀) deficiency currently represents the only treatable mitochondrial disorder, however, little is known about how it may affect other organelles. The lysosome has been found to have a large concentration of CoQ₁₀ localised at its membrane; additionally, it has been suggested that it plays a role in the normal acidification of the lysosomal lumen. As a result, in this study we assessed the effect of CoQ₁₀ deficiency on lysosomal acidification. In order to investigate this, a neuronal cell model of CoQ₁₀ deficiency was established via the treatment of SH-SY5Y cells with para-aminobenzoic acid (PABA). This method works through the competitive inhibition of the CoQ₁₀ biosynthetic pathway enzyme, CoQ₂. A single 1 mM (5 days) treatment with PABA resulted in a decrease of up to 58% in cellular CoQ₁₀ (p < 0.05). It was found that this resulted in a significant decrease in fluorescence of both the LysoSensor (23%) and LysoTracker (35%) probes used to measure lysosomal pH (p < 0.05). It was found that subsequent treatment with CoQ₁₀ (5 µM, 3 days) was able to restore cellular CoQ₁₀ concentration (p < 0.005), which was associated with an increase in fluorescence from both probes to around 90% of controls (p < 0.05), suggesting a restoration of lysosomal pH. This study provides insights into the association between lysosomal pH and cellular CoQ₁₀ status and the possibility that a deficit in the status of this isoprenoid may result in an impairment of lysosomal acidification.

Methylmalonic acidemia is an inborn metabolic disease of propionate catabolism, biochemically characterized by accumulation of methylmalonic acid (MMA) to millimolar concentrations in tissues and body fluids. However, MMA’s role in the pathophysiology of the disorder and its status as a “toxic intermediate” is unclear, despite evidence for its ability to compromise antioxidant defenses and induce mitochondrial dysfunction. Coenzyme Q₁₀ (CoQ₁₀) is a prominent electron carrier in the mitochondrial respiratory chain (MRC) and a lipid-soluble antioxidant which has been reported to be deficient in patient-derived fibroblasts and renal tissue from an animal model of the disease. However, at present, it is uncertain which factors are responsible for inducing this CoQ₁₀ deficiency or the effect of this deficit in CoQ₁₀ status on mitochondrial function. Therefore, in this study, we investigated the potential of MMA, the principal metabolite that accumulates in methylmalonic acidemia, to induce a cellular CoQ₁₀ deficiency. In view of the severe neurological presentation of patients with this condition, human neuroblastoma SH-SY5Y cells were used as a neuronal cell model for this investigation. Following treatment with pathological concentrations of MMA (>0.5 mM), we found a significant (p = 0.0087) ~75% reduction in neuronal cell CoQ₁₀ status together with a significant (p = 0.0099) decrease in MRC complex II–III activity at higher concentrations (>2 mM). The deficits in neuronal CoQ₁₀ status and MRC complex II–III activity were associated with a loss of cell viability. However, no significant impairment of mitochondrial membrane potential (ΔΨm) was detectable. These findings indicate the potential of pathological concentrations of MMA to induce a neuronal cell CoQ₁₀ deficiency with an associated loss of MRC complex II–III activity. However, in the absence of an impairment of ΔΨm, the contribution this potential deficit in cellular CoQ₁₀ status makes towards the disease pathophysiology methylmalonic acidemia has yet to be fully elucidated.

Introduction: Coenzyme Q₁₀ (CoQ₁₀) is a ubiquitous organic molecule with a significant role in the mitochondrial electron transport chain (ETC). As a result of its role in such an important biological process, _CoQ10 deficiency has been implicated in the pathogenesis of numerous diseases such as Parkinson’s disease (PD) and multiple sclerosis (MS). This has led to multiple attempts to use CoQ₁₀ supplementation as a treatment or pre-treatment with varying degrees of success. Areas covered: The present review will identify evidence of mitochondrial dysfunction in MS, PD and mitochondrial ETC disorders. In addition, the inability of Co₁₀ supplementation to elicit significant clinical outcome in these disorders and possible flaws in these studies will be discussed. The databases utilized for this review were the Web of science and PubMed, with inclusive dates (1957–2021). Expert opinion: A lack of improved neurological outcome in these disorders post treatment with CoQ₁₀ may be attributable to the limited ability of CoQ₁₀ to cross the blood–brain barrier. Thus, CoQ₁₀ alternatives should also be considered. Other factors including time of disease diagnosis, dosage, administration, and duration of CoQ₁₀ therapy may have a significant influence on the efficacy of this treatment.