Search Results (100)

Congenital heart diseases (CHDs) are characterized by profound metabolic remodeling of mitochondrial pathways. However, data regarding mitochondrial respiration, oxidative phosphorylation (OXPHOS), and fatty acid oxidation (FAO) in patients with Ebstein anomaly (EA) are currently unavailable. This study evaluated 14 EA patients and 18 healthy volunteers. In accordance with the 2020 ESC guidelines, patients were stratified into two cohorts: EA-0 (patients currently without an indication for intervention) and EA-1 (patients meeting Class Ia or IIb indications for surgical intervention). Platelet OXPHOS and FAO parameters were determined simultaneously via high-resolution respirometry. CI-linked LEAK respiration (substrates: pyruvate and malate) and FAO-linked LEAK respiration (substrates: octanoylcarnitine and malate) were significantly elevated in EA patients. Furthemore, the EA-1 group showed significantly lower coenzyme Q₁₀ (CoQ₁₀) and γ-tocopherol levels than EA-0. Differences in the measured parameters between groups suggest a state of myocardial adaptation and transient metabolic reprogramming in EA-0 patients, whereas in EA-1 patients, a significant change in mitochondrial metabolism and bioenergetics was found. We hypothesize that increased platelet LEAK mitochondrial respiration and CoQ₁₀ deficiency could be key signals of mitochondrial reprogramming and serve as potential biomarkers for right ventricular dysfunction. The analysis of platelet mitochondrial bioenergetics represents a novel area of translational mitochondrial cardiology, contributing to personalized diagnostics, risk stratification and optimal surgical timing in EA patients. Full article

Background: The pathophysiological mechanisms of Abdominal Aortic Aneurysm (AAA) are not elucidated. Alterations in mitochondrial function, such as a reduction in oxidative phosphorylation (OXPHOS), have been observed at genome level and functionally in vascular smooth muscle cells. Metformin reduces AAA development and growth in diabetic patients, but the precise mechanisms are not known. In this paper we aim to demonstrate the feasibility of measuring mitochondrial functional capacity ex vivo in intact murine aneurysmal tissue and confirm a decrease in OXPHOS, and to determine if the protective effect of metformin on AAA is mediated by mitochondrial function. Methods: AAA was induced in ApoE KO mice by administration of angII (1000 ng/kg/min) through osmotic minipumps. Metformin was administered in drinking water at a dose of 100 mg/kg/day. The abdominal aorta was isolated in situ and mitochondrial functional capacity was analyzed ex vivo in whole permeabilized tissue by high-resolution respirometry. Results: Mitochondrial respiration was successfully measured ex vivo in whole aneurysmal tissue. Mitochondrial function was impaired in angII-treated mice, with decreased fold change in Complex I and Complex I+II oxygen consumption, relative to basal levels. Complex II oxygen consumption was also decreased in angII-treated mice. Rescue treatment of mice with metformin did not affect or restore mitochondrial function. Conclusions: Mitochondrial function can be evaluated in murine whole aneurysmal tissue, providing a method for a physiological approach to the study of mitochondrial function in AAA. Mitochondrial function is impaired in AAA. However, rescue treatment with metformin is not sufficient to recover mitochondrial function and seems not to be the mechanism behind prevention of aneurysm. Full article

Pulmonary arterial hypertension (PAH) is characterized by progressive vascular remodeling and right ventricular (RV) dysfunction, processes that are increasingly associated with disturbances in cellular metabolism. We investigated whether transplantation of exogenous mitochondria derived from bone marrow mesenchymal stromal cells, alone or combined with sildenafil, could improve mitochondrial homeostasis and attenuate cardiopulmonary remodeling in monocrotaline-induced PAH. Male Wistar rats were assigned to control (CTRL, n = 8) or PAH (n = 32) groups. Fourteen days after induction of PAH, animals were randomized to receive saline, sildenafil (20 mg/kg/day for 14 days), intravenous mitochondrial transplantation (100 μg, days 14 and 21), or combined therapy. On day 28, echocardiography, invasive measurement of RV systolic pressure (RVSP), pulmonary vascular histology, gene expression analyses (vimentin, VE-cadherin, and mitochondrial metabolism–related genes), and high-resolution respirometry were performed. All treatments significantly reduced RVSP compared with untreated PAH. Mitochondrial therapy, alone or combined with sildenafil, decreased arteriolar α-smooth muscle actin content, whereas endothelial–mesenchymal transition was attenuated only with combined treatment. Mitochondrial transplantation and sildenafil increased Complex I–dependent respiration, whereas Complex IV activity improved exclusively with mitochondrial therapy. Combined treatment reduced plasma IL-6 and IL-1β levels compared with PAH. Thus, mitochondrial transplantation, particularly when combined with sildenafil, improved RV function, limited pulmonary vascular remodeling, reduced plasma inflammatory markers, and changed key mitochondrial pathways in experimental PAH. Full article

Due to their high content of bioactive compounds with anticancer properties, essential oils (EO) are increasingly viewed as valuable therapeutic strategies in oncology. The aim of this study was to evaluate the chemical composition and anticancer activity of Cedrus atlantica EO (CAEO) and its PEG-400 and Tween 20 formulations. The gas-chromatography (GC) analysis revealed a sesquiterpene-rich profile, with β-himachalene (39.32%) as the major constituent, followed by α-Himachalene (16.76%) and γ-Himachalene (12.92%). The cytotoxicity studies, performed using Alamar Blue assay on normal HaCaT human keratinocytes and A375 human melanoma and HT-29 colorectal carcinoma cell lines, revealed that CAEO displayed minimal toxicity on HaCaT cells, while significantly reducing A735 and HT-29 cell viability, at any of the concentrations tested. The PEG- and Tween-based formulations of CAEO exhibited the same effect on cell viability as the simple water dispersion of CAEO. The immunofluorescence-based examination of cellular morphology suggested that CAEO induces apoptosis in both cancer cell lines: A375 and HT-29; this apoptosis-related mechanism was further supported by the caspase-3/7 assay, which revealed a significant increase in caspase-3/7 activity after CAEO treatment. To further investigate the underlying mechanism, the JC-1 staining and high-resolution respirometry assays demonstrated that CAEO induces mitochondrial membrane depolarization and reduced mitochondrial active respiration (OXPHOS). Molecular docking further indicated that isoledene and β-himachalene exhibit the highest predicted affinity for PI3Kγ, suggesting a potential involvement of PI3K-related signaling in the pro-apoptotic activity of CAEO. Together, these results suggest that CAEO induces apoptosis through a mitochondria-mediated mechanism. Full article

Dihydrolipoamide dehydrogenase (DLD) deficiency (MIM #246900) is a rare autosomal recessive mitochondrial disorder caused by pathogenic variants in the DLD gene, which encodes the E3 subunit common to multiple mitochondrial enzyme complexes, including pyruvate dehydrogenase (PDHc) and α-ketoglutarate dehydrogenase (αKGDHc). Although genotype–phenotype correlations have been described, the precise bioenergetic consequences of DLD dysfunction remain poorly defined. Here, we applied high-resolution respirometry using a novel single-run protocol that allows simultaneous assessment of mitochondrial respiratory capacity and, critically, distinguishing between PDHc- and αKGDHc-linked respiration within the same assay. Fibroblasts from six genetically confirmed DLD-deficient patients with distinct pathogenic variants and clinical severities exhibited a consistent reduction in maximal and complex I-linked respiration. The most severe cases (c.1436A>T; p.D479V) showed combined PDHc and αKGDHc impairment, whereas milder genotypes displayed isolated PDHc dysfunction. This mechanistic distinction likely underlies the variable clinical response to ketogenic therapy, which depends on intact αKGDHc function. Analysis of the mitochondrial mass and mtDNA copy number revealed no global reduction, indicating intrinsic enzymatic dysfunction as the primary defect. Collectively, this study defines a reproducible bioenergetic signature of DLD deficiency and introduces an integrated one-run diagnostic strategy for delineating enzyme-specific mitochondrial defects, providing a framework for mechanistic and therapeutic investigations. Full article

Background and Objectives: Fireweed (Chamerion angustifolium L.) possesses antibacterial, antioxidant, anti-inflammatory, and anti-cancer properties. This study evaluated the effects of aqueous fireweed leaf extracts and their major compound, oenothein B, on the viability and mitochondrial function of Caco-2 colon cancer cells, emphasizing the impact of leaf fermentation. Materials and Methods: Cells were treated for 48 h with oenothein B and aqueous extracts from unfermented (NF) and fermented leaves (F 24 h, F 48 h). Cell viability and mitochondrial function were assessed by MTT assay and high–resolution respirometry. Results: IC₅₀ values were 0.843 mg/mL (NF), 1.548 mg/mL (F 24 h), 1.931 mg/mL (F 48 h), and 0.09 mg/mL (57 µM) (oenothein B). Mitochondrial respiration decreased in up to 67% (glutamate/malate) and 61% (succinate) in both fermented and unfermented groups, while oenothein B increased in leak respiration by 34–73% but reduced oxidative respiration by 24%. Conclusions: Aqueous extracts of fireweed from both unfermented and fermented leaves significantly reduced Caco-2 cell viability and mitochondrial function. Oenothein B on its own had a stronger effect on cell viability, but a weaker effect on mitochondrial function, compared to fireweed extracts. Full article

Skeletal muscle, constituting 40–50% of total body mass, is vital for mobility, posture, and systemic homeostasis. Muscle contraction heavily relies on ATP, primarily generated by mitochondrial oxidative phosphorylation. Mitochondria play a key role in decoding intracellular calcium signals. The endocannabinoid system (ECS), including CB₁ receptors (CB₁Rs), broadly influences physiological processes and, in muscles, regulates functions like energy metabolism, development, and repair. While plasma membrane CB₁Rs (pCB₁Rs) are well-established, a distinct mitochondrial CB₁R (mtCB₁R) population also exists in muscles, influencing mitochondrial oxidative activity and quality control. We investigated the role of mtCB₁Rs in skeletal muscle physiology using a novel systemic mitochondrial CB₁ deletion murine model. Our in vivo studies showed no changes in motor function, coordination, or grip strength in mtCB₁ knockout mice. However, in vitro force measurements revealed significantly reduced specific force in both fast-twitch (EDL) and slow-twitch (SOL) muscles following mtCB₁R ablation. Interestingly, knockout EDL muscles exhibited hypertrophy, suggesting a compensatory response to reduced force quality. Electron microscopy revealed significant mitochondrial morphological abnormalities, including enlargement and irregular shapes, correlating with these functional deficits. High-resolution respirometry further demonstrated impaired mitochondrial respiration, with reduced oxidative phosphorylation and electron transport system capacities in knockout mitochondria. Crucially, mitochondrial membrane potential dissipated faster in mtCB₁ knockout muscle fibers, whilst mitochondrial calcium levels were higher at rest. These findings collectively establish that mtCB₁Rs are critical for maintaining mitochondrial health and function, directly impacting muscle energy production and contractile performance. Our results provide new insights into ECS-mediated regulation of skeletal muscle function and open therapeutic opportunities for muscle disorders and aging. Full article

Background/Objectives: Gut-derived tryptophan (Trp) metabolites play important roles in metabolic and cardiovascular regulation. Although animal studies suggest their protective effects against metabolic dysfunction, data in adolescents, particularly those with obesity, remain limited. The objective of this study was to evaluate associations between circulating gut-derived Trp metabolites and markers of cardiometabolic, vascular, and platelet health in adolescents with obesity. Methods: Data were analyzed from 28 adolescents (ages 13–18; mean BMI = 36 ± 6.4 kg/m²). Fasting blood was collected to assess lipid profiles using a clinical analyzer and insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR). Gut-derived Trp metabolites were measured by UPLC–mass spectrometry, peak oxygen uptake (VO_{2 peak}) by gas exchange during an incremental cycle ergometer test, and body composition by dual-energy X-ray absorptiometry. Platelet spare respiratory capacity (SRC), endothelial function, and liver fat were measured using high-resolution respirometry, flow-mediated dilation (FMD) of the brachial artery, and magnetic resonance imaging respectively. Results: Indole-3-propionic acid was inversely associated with diastolic blood pressure (rho = −0.39, p = 0.047), total cholesterol (rho = −0.55, p = 0.002), and LDL-C (rho = −0.57, p = 0.0014), independent of sex and obesity severity. Indoxyl sulfate was positively correlated with fasting glucose (rho = 0.47, p = 0.012), and adolescents with impaired fasting glucose had 1.6-fold higher IS levels. Indole-3-acetaldehyde declined with age (rho = −0.50, p = 0.007), and Indole-3-acetic acid and indole were higher in Hispanics vs. non-Hispanics. No significant associations were observed between Trp metabolites and FMD, VO₂ peak, or SRC. Conclusions: Gut-derived Trp metabolites, particularly indole-3-propionic and indoxyl sulfate, are associated with markers of cardiometabolic risk in adolescents with obesity. These findings support their potential relevance in early-onset cardiovascular disease risk. Full article

Microglia, the resident immune cells of the central nervous system (CNS), play essential roles in maintaining brain homeostasis. While transient activation is protective, chronic microglial reactivity contributes to neuroinflammatory damage and neurodegeneration. The mitochondrial mechanisms underlying this shift remain poorly understood. Here, we investigated whether lipopolysaccharide (LPS) induces coordinated mitochondrial and metabolic alterations in BV-2 microglial cells. LPS stimulation (100 ng/mL, 24 h) induced a reactive phenotype, with increased Iba1 (+82%), F4/80 (+132%), and Cd68 (+44%), alongside elevated hydrogen peroxide (~6-fold) and nitrite (~45-fold). Cytotoxicity increased by 40% (LDH assay), and cell viability dropped to ~80% of the control (MTT). Extracellular lactate increased, indicating glycolytic reprogramming. However, LPS-primed cells showed greater ATP depletion under antimycin A challenge, reflecting impaired metabolic flexibility. Hoechst staining revealed a ~4-fold increase in pyknotic nuclei, indicating apoptosis. Mitochondrial dysfunction was confirmed by a 30–40% reduction in membrane potential (TMRE, JC-1), a ~30% loss of Tomm20, and changes in dynamics: phospho-Drp1 increased (+23%), while Mfn1/2 decreased (33%). Despite a ~70% rise in Lamp2 signal, Tomm20–Lamp2 colocalization decreased, suggesting impaired mitophagy. High-resolution respirometry revealed decreased basal (−22%), ATP-linked (24%), and spare respiratory capacity (41%), with increased non-mitochondrial oxygen consumption. These findings demonstrate that LPS induces mitochondrial dysfunction, loss of metabolic adaptability, and increased apoptotic susceptibility in microglia. Mitochondrial quality control and energy flexibility emerge as relevant targets to better understand and potentially modulate microglial responses in neuroinflammatory and neurodegenerative conditions. Full article

Antibiotics are indispensable in medical patient care, yet they may elicit off-target effects, particularly by affecting mitochondrial function. This study investigates three commonly used antibiotics, gentamicin, ciprofloxacin, and amoxicillin, for their direct effects on mitochondrial respiration and membrane potential. Using high-resolution respirometry, we show that gentamicin and ciprofloxacin markedly increase mitochondrial leak respiration in permeabilized human embryonic kidney cells, suggesting alterations in the mitochondrial inner membrane. This is supported by a gentamicin-induced decrease in mitochondrial membrane potential. Especially gentamicin, but also ciprofloxacin, dose- and time-dependently inhibit oxidative phosphorylation and the mitochondrial electron transfer capacity, pronouncedly in the NADH-linked but also in the succinate-linked pathway. Furthermore, gentamicin decreases Complex IV (CIV) activity in a time-dependent fashion. In contrast, amoxicillin has no significant effect on mitochondrial respiration. These findings emphasize the importance of evaluating the potential direct toxicity of antibiotics on mitochondria, as they are most critical off-target sites. High-resolution respirometry provides a powerful approach to characterize such effects early in the drug development process. Full article

Oregano essential oil (OEO) has gained attention for its broad pharmacological activities, such as anti-inflammatory, antimicrobial, and anticancer properties. This study aimed to analyze the phytochemical composition and biological activity of OEO obtained from wild-growing Origanum vulgare L. in Romania. Gas chromatography–mass spectrometry (GC–MS) analysis identified p-cymene (43.98%), γ-terpinene (22.16%), and thymol (11.46%) as major constituents, with notable differences from previously reported chemotypes. Antioxidant activity was assessed using the DPPH, ABTS radical scavenging assay, and TPC. OEO has a moderate antioxidant activity, with IC₅₀ values of 134.67 ± 1.32 µg/mL (DPPH) and 88.15 ± 0.045 Inh% (ABTS) and a TPC of 159.63 mg GAE/g extract. The cytotoxicity of the simple water dispersion of OEO, OEO solubilized with polyethylene glycol 400 (OEO-PEG), and that solubilized with Tween 20 (OEO-Tw) was evaluated on human melanoma (A375) and human colorectal adenocarcinoma (HT-29) cancer cell lines, as well as on the normal human immortalized keratinocytes (HaCaT) cell line. The results demonstrated a significant inhibition of cancer cell viability with no recorded cytotoxic effect on normal cells. The highest inhibition of cell viability was recorded for OEO-PEG 200 µg/mL (7.22% ± 6.51 in A375 cell line and 22.25% ± 10.08 in HT-29 cell line). In cancer cells, OEO and its formulations significantly reduced malondialdehyde (MDA) levels (up to 41.24% in A375 cells and up to 48.58% in HT-29 cells), suggesting potent antioxidant activity. Moreover, treatment with OEO increased caspase 3/7 activation two-fold in treated A375 cells, while high-resolution respirometry studies revealed that OEO induces mitochondrial dysfunction by acting as a potential uncoupling agent. Molecular docking analysis suggested that β-caryophyllene oxide (CPO), a minor constituent of OEO, may act as a potential inhibitor of 3-phosphoinositide-dependent protein kinase-1 (PDPK1), indicating a possible mechanism of anticancer activity. Our findings highlight the potential of OEO as a natural anticancer agent, emphasizing the need for further investigations to elucidate its exact molecular mechanisms and therapeutic applicability. Full article

Background: The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant MT-CYB:m.15309T>C (Ile188Thr). Methods: We provide detailed analysis of the clinical examinations of a male patient with bilateral optic neuropathy from the acute stage to 8 years of follow-up. Complete ophthalmological exam, electrophysiology and optical coherence tomography (OCT) segmentation were performed. The genotype analysis was performed with a complete screening of the mitochondrial genome. Furthermore, proteomic analysis of the protein structure and function was performed to assess the pathogenicity of a novel variant of unknown significance. Mitochondrial function analysis of the patient’s peripheral blood mononuclear cells (PBMCs) was performed with the objective of evaluating the mutation effect on mitochondrial function using flow cytometry and high-resolution respirometry. Results: The patient had a profound consecutive bilateral visual loss at 19 years of age due to optic neuropathy with characteristics of LHON; however, unlike patients with typical LHON, the patient experienced a fluctuation in visual function and significant late recovery. He had a total of three visual acuity deteriorations and improvements in the left eye, with concomitant visual loss in the right eye and a final visual acuity drop reaching nadir 9 months after onset. The visual loss was characterized by centrocecal scotoma, abnormal color vision and abnormal VEP, while deterioration of PERG N95 followed with a lag of several months. The OCT examination showed retinal nerve fiber layer thinning matching disease progression. Following a two-year period of legal blindness, the patient’s visual function started to improve, and over the course of 5 years, it reached 0.5 and 0.7 Snellen (0.3 and 0.15 LogMAR) visual acuity (VA). Mitochondrial sequencing identified a presumably pathogenic variant m.15309T>C in the MT-CYB gene at 65% heteroplasmy, belonging to haplogroup K. Mitochondrial function assessment of the patient’s PBMCs showed a lower respiration rate, an increase in reactive oxygen species production and the presence of mitochondrial depolarization, compared to an age- and sex-matched healthy control’s PBMCs. Conclusions: A novel variant in the MT-CYB:m.15309T>C (Ile188Thr) gene was identified in a patient with optic nerve damage and the LHON phenotype without any additional systemic features and atypical presentation of the disease with late onset of visual function recovery. The pathogenicity of the variant is supported by proteomic analysis and the mitochondrial dysfunction observed in the patient’s PBMCs. Full article

Background/Objectives: Early postmortem mitochondrial function and apoptotic activation affect meat quality development. Nicotinamide riboside (NR) supplementation to pigs prior to harvest can improve pork color stability, but its mechanism remains unclear. This study aimed to evaluate the impact of NR supplementation on early postmortem mitochondrial functionality and apoptosis. Methods: Sixteen pigs (N = 16) were individually fed a control or NR-supplemented diet (30 mg·kg body weight⁻¹·d⁻¹) for 10 days prior to harvest. Longissimus dorsi muscle samples were collected at 45 min and 24 h postmortem and analyzed for mitochondrial functionality using high-resolution respirometry and apoptotic protein abundance (apoptosis regulator Bcl-2-associated X (BAX), apoptotic inducing factor (AIF), and caspase 3 (CASP3)) via immunoblotting. Results: NR-supplemented muscle exhibited lower proton leak-associated respiration at 45 min postmortem (p < 0.05), followed by a slower accumulation of mitochondrial outer membrane permeabilization (MOMP; p < 0.05) and a slower loss of mitochondrial integral function (p < 0.05) from 45 min to 24 h postmortem. NR supplementation decreased BAX abundance at 45 min postmortem but increased mature AIF abundance (62 kDa) at 24 h postmortem (p < 0.05). The abundance of CASP3 fragments (~29 kDa) decreased from 45 min to 24 h postmortem, independent of treatment (p < 0.05). Conclusions: NR supplementation demonstrated the potential to protect mitochondrial integral function and alleviate apoptotic activation in early postmortem porcine skeletal muscle, which might contribute to a higher meat color stability in NR-supplemented pork during retail display. 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

Menopause occurs due to the depletion of the ovarian reserve, leading to a progressive decline in estrogen (E2) levels. This decrease in E2 levels increases the risk of developing several diseases and can coexist with chronic kidney disease (CKD). Arterial hypertension (AH) is another condition associated with menopause and may either contribute to or result from CKD. Ovariectomy (OVX) induces hypoestrogenism, which can lead to mitochondrial bioenergetic dysfunction in the kidneys. Previous studies have suggested that exercise training has beneficial effects on adults with CKD and AH. To investigate the effects of OVX and resistance training (RT) on hemodynamic parameters and mitochondrial bioenergetic function of the kidney, female Wistar rats were divided into ovariectomized (OVX) and intact (INT) groups. These rats were either kept sedentary (SED) or subjected to RT for thirteen weeks. The RT involved climbing a vertical ladder with a workload apparatus. Hemodynamic parameters were assessed via tail plethysmography. Mitochondrial respiratory function was evaluated with high-resolution respirometry. Gene expression related to the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS) was evaluated by real-time qPCR. At week 13, key hemodynamic parameters (systolic blood pressure and mean arterial pressure) were significantly elevated in the OVX-SED group. Compared with those in the other groups, mitochondrial bioenergetics were impaired in the OVX-SED group. In contrast, the trained groups presented improved mitochondrial bioenergetic function compared with the sedentary groups. OVX led to reduced gene expression related to the mitochondrial ETC and OXPHOS, whereas RT both prevented this reduction and increased gene expression in the trained groups. Our results indicate that hypoestrogenism significantly decreases OXPHOS and ETC capacity in the kidneys of sedentary animals. However, RT effectively increased the expression of genes related to mitochondrial ETC and OXPHOS, thereby counteracting the effects of OVX. Full article