Search Results (150)

Glutamate dehydrogenase (GDH) is ubiquitous in organisms and crucial for amino acid metabolism, energy production, and redox balance. The gdhA and gudB genes encoding GDH were identified in Bacillus altitudinis AS19 and shown to be regulated by iron. However, their functions remain unclear. In this study, gdhA and gudB were analyzed using bioinformatics tools, such as MEGA, Expasy, and SWISS-MODEL, expressed with a prokaryotic expression system, and the induction conditions were optimized to increase the yield of soluble proteins. Phylogenetic analysis revealed that GDH is evolutionarily conserved within the genus Bacillus. GdhA and GudB were identified as hydrophobic proteins, not secreted or membrane proteins. Their structures were primarily composed of irregular coils and α-helices. SWISS-MODEL predicts GdhA to be an NADP-specific GDH, whereas GudB is an NAD-specific GDH. SDS-PAGE analysis showed that GdhA was expressed as a soluble protein after induction with 0.2 mmol/L IPTG at 24 °C for 16 h. GudB was expressed as a soluble protein after induction with 0.1 mmol/L IPTG at 16 °C for 12 h. The proteins were confirmed by Western blot and mass spectrometry. The enzyme activity of recombinant GdhA was 62.7 U/mg with NADPH as the coenzyme. This study provides a foundation for uncovering the functions of two GDHs of B. altitudinis AS19. Full article

Nitrogen-containing bisphosphonates (N-BPs) are commonly used drugs in the treatment of bone diseases due to their potent inhibition of the mevalonate pathway, leading to disrupted protein prenylation and reduced osteoclast activity. Although N-BPs are effective in reducing bone resorption, increasing evidence indicates their side effects on various non-skeletal cells. The aim of this review is to synthesize the current knowledge on the cellular and molecular effects of N-BPs outside the skeletal system, with particular emphasis on their impact on mitochondrial function and energy metabolism. At the cellular level, N-BPs may reduce viability, modulate inflammatory responses, trigger apoptosis, disrupt cytoskeletal organization, and influence signaling and energy metabolism. N-BPs may also impair the prenylation of proteins essential for mitochondrial dynamics and quality control, and may disrupt Ca²⁺ homeostasis. As we have shown in endothelial cells, by inhibiting the mevalonate pathway, N-BPs may lead to a reduction in key components of the mitochondrial respiratory chain, such as coenzyme Q (CoQ) and a-heme. These effects can contribute to impaired mitochondrial respiratory function, increased oxidative stress, and mitochondria-dependent apoptosis, affecting cellular energy metabolism and viability. These findings underscore the multifaceted impact of N-BPs beyond bone, emphasizing the importance of mitochondrial health and energy metabolism in understanding their broader biological effects and potential adverse outcomes. Full article

The physiological functions of mammalian sperm, such as motility, hyperactivation, and capacitation, require substantial energy. This study investigates the effects of two classic cryopreservation extenders—TCG (tris-citrate-glucose) and LEY (lactose-egg yolk)—on the energy metabolism of frozen–thawed boar semen. By comparing the quality indicators, key metabolite levels, and the activities of critical enzymes involved in glycolysis and the tricarboxylic acid cycle, we aim to understand how these different semen extenders influence the spermatozoa vitality of frozen–thawed boar semen. Following thawing, the LEY-cryopreserved sperm demonstrated significantly elevated motility parameters (viability, VCL, VSL, and VAP) and enhanced plasma membrane and acrosomal integrity compared with the TCG group (p < 0.05), though both cryopreserved groups exhibited significantly reduced performance relative to fresh semen controls. Cryopreservation markedly reduced intracellular adenosine triphosphate (ATP), pyruvate, and acetyl coenzyme A (A-CoA) levels (fresh > LEY > TCG; p < 0.05). The LEY-preserved spermatozoa retained higher activities of glycolysis-related enzymes (phosphofructokinase, PFK; pyruvate kinase, PK) compared with the TCG group, which, in turn, showed elevated lactate dehydrogenase (LDH) activity. Critically, TCG-suppressed pyruvate dehydrogenase (PDH) activity (p < 0.05) coincided with diminished A-CoA, indicating impaired mitochondrial oxidative phosphorylation. These results demonstrate LEY’s superior preservation of motility and membrane stability but highlight cryodamage-induced energy metabolism dysregulation, particularly TCG’s disruption of the glycolysis–TCA cycle coordination essential for spermatozoa function. In conclusion, the choice of semen extender has a significant impact on the energy metabolism and overall quality of frozen–thawed semen, highlighting the importance of optimizing cryopreservation protocols for improved spermatozoa viability and functionality. Full article

Background and Objectives: Obesity is linked to liver cancer through metabolic mechanisms and can promote tumor growth through metabolic impairment, decreased lipid metabolism, and interference of the energy balance in the liver. NAMPT is an enzyme expressed in the liver and is involved in the progression of tumors in obesogenic environments, while iNAMPT is known to be the rate-limiting enzyme in the synthesis of NAD, an essential coenzyme involved in ATP synthesis which promotes a pro-growth environment in the context of obesity. Because iNAMPT and cellular energetics, a hallmark of cancer, play an important role in liver cancer progression, it has become a target for cancer therapies focused on inhibiting its functions. The objective of this study was to determine the contribution of NAD biosynthesis in obesity-associated liver cancer progression. Methods: Cell culture studies were conducted with serum from male mice randomized to diet-induced obesity (OB) or control (CR) ± FK866 (iNAMPT inhibitor) in SNU, HepG2 human liver cancer cells, and Hepa 1-6 liver murine cells. Protein analysis of pAkt and pErk was performed via immunoblot. Cytotoxicity, reactive oxygen species (ROS), cell viability, and invasion were also measured in the cells. For the mouse model, the C57BL/6J male mice were randomized to the DIO or CR group. At 21 weeks of age, the mice were injected subcutaneously with Hepa 1-6 liver cancer cells. At 23 weeks, the mice received an I.P. injection of FK866 (30 mg/kg) for 2 weeks. The tumor and mouse weights were measured. Results: The cells exposed to OB sera showed increased proliferation, lactate dehydrogenase (LDH) secretion, ROS, and invasion. FK866 decreased proliferation, LDH secretion, ROS, and invasion for all liver cancer cells. The cells exposed to CR sera and OB + FK866 resulted in more LDH, suggesting increased apoptosis compared with OB sera. The OB sera increased phosphorylation of Akt, which was suppressed by FK866 compared with the OB group. In liver cancer cells, physiological and cellular signaling is affected differently when inhibiting NAD biosynthesis in an in vitro model of obesity and liver cancer. In vivo, the diet-induced obese (DIO) mice weighed significantly more than the mice fed a control diet. In addition, 70% of the DIO mice developed tumors, compared with 20% of the CR mice, and had tumors with greater volumes and weights. NAD inhibition blocked obesity-induced tumor growth. Conclusions: In this study, we demonstrate that inhibition of iNAMPT resulted in suppression of tumor growth in the context of obesity. Identifying pre-clinical strategies to reverse the impact of obesity on liver cancer progression is important due to the strong increased risk of liver cancer and its poor prognosis. Future translational research studies can be built from this pre-clinical foundational research. Full article

Objectives: The aim of this study was to evaluate the impact of a novel antioxidant formulation (RE:PAIR, RP-25) containing CoQ10, alpha-lipoic acid, and Chaga extract on mitochondrial dysfunction and oxidative stress. To explore the activity of the formulation on neuronal cells, we explored cell metabolism and its activity as an antioxidant, using a combination of NMR-based metabolomics and UHPLC-HRMS analytical techniques. Methods: SH-SY5Y neuroblastoma cells were treated with RP-25, and cell viability was assessed via CCK-8 assay. Metabolomic profiles of the treated and untreated cells were analyzed by 1D-NMR, providing insights into both intracellular metabolites (endometabolome) and excreted metabolites (exometabolome). Additionally, a UHPLC-HRMS method was developed for quality control and analysis of the RP-25 formulation. Multivariate statistical approaches, including PLS-DA and volcano plot analyses, were used to identify key metabolic changes. Changes in mitochondrial membrane potential were assessed by means of TMRE assay, while radical oxygen species (ROS) were measured by means of the DCHF assay. Results: RP-25 treatment did not affect cell viability but significantly increased metabolic pathways, including amino acid biosynthesis, oxidative phosphorylation, and glycolysis. Higher levels of ATP, glutamate, tyrosine, and proline were observed in treated cells than in control cells, indicating enhanced cellular energy production, as also proved by the increased stability of the mitochondrial membrane after RP-25 treatment, an index of preserved mitochondrial functions. In support, the formulation RP-25 showed antioxidant activity when cells underwent peroxide oxygen stimulation. This effect was mainly due to the combination of Chaga, CoQ10, and ALA, main components of the RP25 formulation. Moreover, the analysis of enriched pathways highlighted that RP formulation influenced mitochondrial energy and oxidative stress response. Conclusions: RP-25 demonstrated biological activity in that it mitigated mitochondrial dysfunction and oxidative stress in neuronal cells, with potential implications in neuronal diseases associated with dysfunctional mitochondria. Full article

AarF domain-containing kinases (ADCKs) are a family of putative mitochondrial proteins that have been implicated in various aspects of mitochondrial function and cellular metabolism. Mitochondria play a crucial role in cellular bioenergetics, primarily in adenosine triphosphate (ATP) production, while also regulating metabolism, thermogenesis, apoptosis, and reactive oxygen species (ROS) generation. Evidence suggests that the ADCK family of proteins is involved in maintaining mitochondrial architecture and homeostasis. In detail, these proteins are believed to play a role in processes such as coenzyme Q biosynthesis, energy production, and cellular metabolism. There are five known isoforms of ADCK (ADCK1–ADCK5), some of which have similar activities, and each also has its own unique biological functions. Dysregulation or mutations in specific ADCK isoforms have been linked to several pathological conditions, including multiple human cancers, primary coenzyme Q10 (CoQ10) deficiency, and metabolic disorders. This review surveys the current body of peer-reviewed research on the ADCK protein family, incorporating data from the primary literature, case studies, and experimental studies conducted in both in vitro and in vivo systems. It also draws on existing review articles and known published findings to provide a comprehensive overview of the functional roles, disease associations, and molecular mechanisms of ADCK proteins. Further in-depth research on ADCK proteins has the potential to unlock critical insights into their precise mechanisms. This could pave the way for identifying new therapeutic targets for mitochondrial and metabolic-related diseases, as well as for advancing cancer treatment strategies. Full article

Heart failure represents the terminal stage in the development of many cardiovascular diseases, and its pathological mechanisms are closely related to disturbances in energy metabolism and mitochondrial dysfunction in cardiomyocytes. In recent years, nicotinamide adenine dinucleotide (NAD⁺), a core coenzyme involved in cellular energy metabolism and redox homeostasis, has been shown to potentially ameliorate heart failure through the regulation of mitochondrial function. This review systematically investigates four core mechanisms of mitochondrial dysfunction in heart failure: imbalance of mitochondrial dynamics, excessive accumulation of reactive oxygen species (ROS) leading to oxidative stress injury, dysfunction of mitochondrial autophagy, and disturbance of Ca²⁺ homeostasis. These abnormalities collectively exacerbate the progression of heart failure by disrupting ATP production and inducing apoptosis and myocardial fibrosis. NAD⁺ has been shown to regulate mitochondrial biosynthesis and antioxidant defences through the activation of the deacetylase family (e.g., silent information regulator 2 homolog 1 (SIRT1) and SIRT3) and to increase mitochondrial autophagy to remove damaged mitochondria, thus restoring energy metabolism and redox balance in cardiomyocytes. In addition, the inhibition of NAD⁺-degrading enzymes (e.g., poly ADP-ribose polymerase (PARP), cluster of differentiation 38 (CD38), and selective androgen receptor modulators (SARMs)) increases the tissue intracellular NAD⁺ content, and supplementation with NAD⁺ precursors (e.g., β-nicotinamide mononucleotide (NMN), nicotinamide riboside, etc.) also significantly elevates myocardial NAD⁺ levels to ameliorate heart failure. This study provides a theoretical basis for understanding the central role of NAD⁺ in mitochondrial homeostasis and for the development of targeted therapies for heart failure. Full article

Global kelp farming is garnering growing attention for its contributions to fishery yields, environmental remediation, and carbon neutrality efforts. Kelp farming systems face escalating pressures from compounded climatic and environmental stressors. A severe outbreak disaster caused extensive kelp mortality and significant economic losses in Rongcheng, China, one of the world’s largest kelp farming areas. This study investigated the growth and physiological responses of Saccharina japonica to combined stressors involving three levels of N:P ratios (10:1 as a control; 100:1 and 500:1 to represent phosphorus deficiency stress) and two temperature/light regimes (12 °C, 90 μmol photons m⁻² s⁻¹ as a control, and 17 °C, 340 μmol photons m⁻² s⁻¹ to represent thermal and high-light stress). The results demonstrated that phosphorus deficiency significantly inhibited the relative growth rate of kelp (24% decrease), and the strongest growth inhibition in kelp was observed at the N:P ratio of 500:1 combined with thermal and high-light stress. The algal tissue was whitened due to its progressive disintegration under escalating stress, coupled with damage to its chloroplasts and nucleus ultrastructures. Phosphorus-deficiency-induced declines in photochemistry (27–56% decrease) and chlorophyll content (63% decrease) were paradoxically and transiently reversed by thermal and high-light stress, but this “false recovery” accelerated subsequent metabolic collapse (a 60–75% decrease in the growth rate and a loss of thallus integrity). Alkaline phosphatase was preferentially activated to cope with phosphorus deficiency combined with photothermal stress, while acid phosphatase was subsequently induced to provide auxiliary support. S. japonica suppressed its metabolism but upregulated its nucleotides under phosphorus deficiency; however, the energy/amino acid/coenzyme pathways were activated and a broad spectrum of metabolites were upregulated under combined stressors, indicating that S. japonica employs a dual adaptive strategy where phosphorus scarcity triggers metabolic conservation. Thermal/light stress can override phosphorus limitations by activating specific compensatory pathways. The findings of this study provide a foundation for the sustainable development of kelp farming under climate and environmental changes. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder. Camellia seed cake, a byproduct of oil extraction, contains a variety of bioactive compounds. This study investigated the regulatory effects and underlying mechanisms of camellia seed cake extract (CSCE) using a high-fat diet (HFD)-induced MASLD mouse model. Methods: Mice were divided into four groups: normal control (N, standard diet), HFD model (M), HFD-fed mice treated with low-dose CSCE (L), and HFD-fed mice treated with high-dose CSCE (H). CSCE was administered via oral gavage for eight weeks. Body weight, blood lipid levels, liver weight, hepatic lipid accumulation, oxidative stress markers, ATP levels, and the NADH/NAD⁺ ratio were measured. Transcriptomic and lipidomic analyses were performed to identify potential regulatory pathways, and qPCR analysis was conducted to confirm the expression levels of essential genes. Results: CSCE significantly reduced HFD-induced increases in body and liver weights, improved blood lipid profiles and hepatic lipid accumulation, alleviated oxidative stress, increased ATP levels, and reduced the NADH/NAD⁺ ratio. Transcriptomic analysis demonstrated notable enrichment of genes associated with oxidative phosphorylation, mitochondrial function, and lipid metabolism after treatment. The lipidomic analysis demonstrated that the hepatic lipid profile of the H group approached that of the N group, with Coenzyme Q9 (CoQ9) and Coenzyme Q10 (CoQ10) levels significantly increased by 173.32% and 202.73%, respectively, compared to the M group. qPCR validation confirmed that CoQ synthesis-related genes (Coq2–10, Pdss1, Pdss2, and Hmgcr) were significantly upregulated in the treatment groups. Conclusions: CSCE enhances mitochondrial function by promoting CoQ synthesis, alleviates metabolic dysfunction, and could represent a potential natural intervention for MASLD. Full article

Migraine, with a prevalence of 14–15% in the world population, is one of the diseases that markedly reduce patients’ quality of life. Despite extensive therapeutic tools, the search for substances that may have potential therapeutic properties in migraine patients is still ongoing. Coenzyme Q10 (CoQ10), as a natural and potent antioxidant, appears to be a valuable adjunct in treating and preventing many conditions, such as cardiovascular, metabolic, autoimmune, or neurodegenerative diseases. This review aims to evaluate if CoQ10 can be a potential therapeutic agent in the treatment of migraine. Based on the studies discussed, CoQ10 may have applications in migraine therapy due to its potent anti-inflammatory and oxidative stress-reducing properties. Furthermore, by improving mitochondrial function, CoQ10 can contribute to the energy supply to brain cells, which is particularly important in migraine. Supplementation with CoQ10 in a wide range of doses has resulted in many therapeutic benefits in subjects, including a decrease in the frequency and duration of migraine attacks, a reduction in nausea, a lower maximum pain during an attack, and fewer days with migraine. Therefore, it seems that CoQ10 may be a relevant therapeutic supplement for the treatment and prevention of migraine. Full article

Coenzyme Q₁₀ (CoQ₁₀) is a molecule that serves as a coenzyme for mitochondrial enzymes, playing a fundamental role in mitochondrial bioenergetics as an electron and proton carrier in the energy production process. This study aimed to examine the modulatory effects of moderate/high-intensity exercise and CoQ₁₀ supplementation on tumstatin, lipid dynamics, and body mass in rats. This study used 42 male Wistar Albino rats in six groups: a control group (C), a moderate-intensity continuous training group (MICT), a high-intensity continuous training group (HICT), a coenzyme Q₁₀ group (Q₁₀), a moderate-intensity continuous training combined with Q₁₀ group (MICTQ₁₀), and a high-intensity continuous training combined with Q₁₀ group (HICTQ₁₀) to assess the effects of exercise and 5 mg/kg/daily CoQ₁₀ supplementation. Rats underwent treadmill training, and tumstatin levels in plasma, cardiac, and skeletal muscle tissues were measured using ELISA and immunostaining techniques. In addition to the plasma, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC) levels were analyzed using enzymatic methods, with the LDL-C calculated using the Friedewald equation. The atherogenic index of plasma was determined by the TG/HDL-C ratio. As compared to group C, body mass was significantly affected by both exercise intensity and supplementation (p = 0.01, η² = 0.37), with the MICTQ₁₀ and HICTQ₁₀ groups demonstrating the greatest reductions by day 50th (p = 0.0003, d = 4.02; p = 0.0001, d = 3.99). Lipid profiles varied significantly between groups. Compared to the C group, the MICTQ₁₀ group exhibited the most substantial decreases in LDL-C (p = 0.03, d = 2.35) and TG levels (p = 0.03, d = 2.25), while the HICTQ₁₀ group showed the most pronounced reduction in TC levels (p = 0.001, d = 6.41). Regarding tumstatin levels, skeletal muscle tumstatin levels were lowest in the HICTQ₁₀ group (p = 0.01, d = 2.11). Moreover, cardiac muscle tumstatin levels were significantly lower in the MICTQ₁₀, MICT, and HICTQ₁₀ groups compared to in the C group (p = 0.004, d = 1.01). These findings suggest that both exercise intensity and CoQ₁₀ supplementation exert notable physiological effects, particularly in modulating body mass, lipid metabolism, and tumstatin levels. Full article

Post-exertional malaise (PEM) is a defining condition of myalgic encephalomyelitis (ME/CFS). The concept requires that a provocation causes disabling limitation of cognitive and functional effort (“fatigue”) that does not respond to rest. Cerebrospinal fluid was examined as a proxy for brain metabolite and lipid flux and to provide objective evidence of pathophysiological dysfunction. Two cohorts of ME/CFS and sedentary control subjects had lumbar punctures at baseline (non-exercise) or after submaximal exercise (post-exercise). Cerebrospinal fluid metabolites and lipids were quantified by targeted Biocrates mass spectrometry methods. Significant differences between ME/CFS and control, non-exercise vs. post-exercise, and by gender were examined by multivariate general linear regression and Bayesian regression methods. Differences were found at baseline between ME/CFS and control groups indicating disease-related pathologies, and between non-exercise and post-exercise groups implicating PEM-related pathologies. A new, novel finding was elevated serine and its derivatives sarcosine and phospholipids with a decrease in 5-methyltetrahydrofolate (5MTHF), which suggests general dysfunction of folate and one-carbon metabolism in ME/CFS. Exercise led to consumption of lipids in ME/CFS and controls while metabolites were consumed in ME/CFS but generated in controls. In general, the frequentist and Bayesian analyses generated complementary but not identical sets of analytes that matched the metabolic modules and pathway analysis. Cerebrospinal fluid is unique because it samples the choroid plexus, brain interstitial fluid, and cells of the brain parenchyma. The quantitative outcomes were placed into the context of the cell danger response hypothesis to explain shifts in serine and phospholipid synthesis; folate and one-carbon metabolism that affect sarcosine, creatine, purines, and thymidylate; aromatic and anaplerotic amino acids; glucose, TCA cycle, trans-aconitate, and coenzyme A in energy metabolism; and vitamin activities that may be altered by exertion. The metabolic and phospholipid profiles suggest the additional hypothesis that white matter dysfunction may contribute to the cognitive dysfunction in ME/CFS. Full article

The contemporary approach to nutrition increasingly considers the role of non-nutritive bioactive compounds in modulating the immune system and maintaining health. This article provides up-to-date insight into the immunomodulatory effects of selected bioactive compounds, including micro- and macronutrients, vitamins, as well as other health-promoting substances, such as omega-3 fatty acids, probiotics, prebiotics, postbiotics (including butyric acid and sodium butyrate), coenzyme Q10, lipoic acid, and plant-derived components such as phenolic acids, flavonoids, coumarins, alkaloids, polyacetylenes, saponins, carotenoids, and terpenoids. Micro- and macronutrients, such as zinc, selenium, magnesium, and iron, play a pivotal role in regulating the immune response and protecting against oxidative stress. Vitamins, especially vitamins C, D, E, and B, are vital for the optimal functioning of the immune system as they facilitate the production of cytokines, the differentiation of immunological cells, and the neutralization of free radicals, among other functions. Omega-3 fatty acids exhibit strong anti-inflammatory effects and enhance immune cell function. Probiotics, prebiotics, and postbiotics modulate the intestinal microbiota, thereby promoting the integrity of the intestinal barrier and communication between the microbiota and the immune system. Coenzyme Q10, renowned for its antioxidant attributes, participates in the protection of cells from oxidative stress and promotes energy processes essential for immune function. Sodium butyrate and lipoic acid exhibit anti-inflammatory effects and facilitate the regeneration of the intestinal epithelium, which is crucial for the maintenance of immune homeostasis. This article emphasizes the necessity of an integrative approach to optimal nutrition that considers not only nutritional but also non-nutritional bioactive compounds to provide adequate support for immune function. Without them, the immune system will never function properly, because it has been adapted to this in the course of evolution. The data presented in this article may serve as a foundation for further research into the potential applications of bioactive components in the prevention and treatment of diseases associated with immune dysfunction. Full article

Climate change and the energy crisis, driven by excessive CO₂ emissions, have emerged as pressing global challenges. The conversion of CO₂ into high-value chemicals not only mitigates atmospheric CO₂ levels but also optimizes carbon resource utilization. Enzyme-catalyzed carbon technology offers a green and efficient approach to CO₂ conversion. However, free enzymes are prone to inactivation and denaturation under reaction conditions, which limit their practical applications. Metal–organic frameworks (MOFs) serve as effective carriers for enzyme immobilization, offering porous crystalline structures that enhance enzyme stability. Moreover, their high specific surface area facilitates strong gas adsorption, making enzyme@MOF composites particularly advantageous for CO₂ catalytic conversion. In this paper, we review the synthesis technologies and the application of enzyme@MOFs in CO₂ catalytic conversion. Furthermore, the strategies, including the enhancement of CO₂ utilization, coenzyme regeneration efficiency, and substrate mass transfer efficiency, are also discussed to further improve the efficiency of enzyme@MOFs in CO₂ conversion. The aim of this review is to present innovative ideas for future research and to highlight the potential applications of enzyme@MOFs in achieving efficient CO₂ conversion. Full article

Fertility disorders are a worldwide problem affecting 8–12% of the population, with the male factor substantially contributing to about 40–50% of all infertility cases. Mitochondria, crucial organelles for cellular viability, play a pivotal role in the processes of spermatogenesis and significantly affect sperm quality and their fertilizing ability. Mitochondrial oxidative phosphorylation (OXPHOS) dysfunction, reduced energy supply for sperm, reduced endogenous coenzyme Q₁₀ (CoQ₁₀) levels, and oxidative stress are among the main factors that contribute to male infertility. There is great interest in the role of mitochondrial dysfunction in male infertility, and the diagnosis and assessment of mitochondrial health in infertile men present challenges. Platelets are a source of viable mitochondria that can be obtained non-invasively. Changes in platelet mitochondrial respiration were documented in various diseases, confirming platelet mitochondrial bioenergetics as a marker of systemic mitochondrial health. The aim of our study was to determine whether (a) platelet mitochondrial bioenergetics and CoQ₁₀ levels could be used as metabolic markers of mitochondrial health in infertile men and whether (b) the parameters of mitochondrial respiration in platelets correlate with sperm parameters. The high-resolution respirometry method was used for platelet bioenergetics, and the high-performance liquid chromatography (HPLC) method was used for CoQ₁₀ level measurement. The static oxidation–reduction potential (sORP) of the ejaculate was evaluated by MiOXSYS^®System. We found a deficit in mitochondrial complex I-linked OXPHOS and electron transfer capacity and CoQ₁₀ and α-tocopherol levels in infertile men. The proportion of sperm, heads, and midpiece abnormalities correlated negatively with the complex I-linked parameters of platelet mitochondrial bioenergetics. We suppose that dysfunctional mitochondria contribute to increased oxidative stress, and these imbalances can be considered a cause of Male Oxidative Stress Infertility (MOSI). Our results suggest that platelet mitochondrial function and the endogenous levels of CoQ₁₀ in platelets could be used as metabolic markers for monitoring mitochondrial health and targeted therapy in infertile men. sORP could be a useful clinical biomarker of MOSI. Full article