Search Results (258)

Alveolar echinococcosis (AE) is a fatal foodborne parasitic disease caused by the larvae of Echinococcus multilocularis. The disease primarily affects the liver. Previous studies have found that Kupffer cells have an immune protective effect, but in the late stages of AE, they are associated with parasite immune escape. The present study analyzed the effects of Echinococcus multilocularis protoscoleces (PSCs) infection on the mitochondrial morphology and function of macrophages, as well as their phagocytic function and apoptosis. Infection with PSCs has been shown to result in the fragmentation of the macrophage mitochondrial network, the impairment of mitochondrial membrane potential, the elevation of mitochondrial reactive oxygen species, and the reduction in mitochondrial DNA copy number. This cascade of events, consequent to the infection, has been demonstrated to promote the apoptosis of macrophages and impair their phagocytic function. Inhibiting mitochondrial fission during PSCs infection has been shown to mitigate mitochondrial dysfunction, suppress macrophage apoptosis, and enhance macrophage phagocytic function. This discovery provides insights into improving macrophage function during the progression of AE. Full article

Mitochondria play a central role in energy metabolism, redox homeostasis, and signal transduction in the thyroid cells. Increasing evidence indicates that mitochondrial DNA (mtDNA) mutations, copy number variations, and haplogroup-specific polymorphisms are closely associated with metabolic reprogramming and malignant progression of thyroid cancer. This review summarizes recent advances in the understanding of the impact of mitochondrial genome instability and metabolic plasticity on thyroid tumorigenesis. We discuss how mtDNA alterations disrupt oxidative phosphorylation (OXPHOS), trigger adaptive metabolic rewiring, and interact with key oncogenic pathways, such as HIF-1α, BRAFV600E mutations, and TSHR signaling in thyroid cancer. We also highlight the emerging diagnostic and therapeutic potential of mtDNA in thyroid cancer and outline current challenges and future research directions. Gaining deeper insights into the mitochondria–metabolism axis may provide novel biomarkers and metabolic intervention strategies for precision medicine in thyroid oncology. Full article

Background and Objectives: Acute kidney injury (AKI) is a common complication in patients with trauma and is associated with increased morbidity and mortality rates. Early identification of patients at risk of AKI may enable timely intervention and improved outcomes. Biomarkers such as urinary mitochondrial DNA copy number (mtDNAcn) may play a role in predicting AKI. However, its role as a predictor of AKI has rarely been studied in patients with trauma. Therefore, the aim of this study was to evaluate the utility of mtDNA for early detection of AKI in this patient population. Materials and Methods: This single-center prospective observational study included patients with trauma admitted to a regional trauma center between July 2022 and July 2023. Serum and urine samples were collected at baseline and at 24, 48, and 72 h to measure mtDNAcn using real-time polymerase chain reaction test. Clinical variables, including hemoglobin (Hb) levels, were also recorded. Results: Among 65 enrolled patients, 25 (38.5%) developed AKI. Patients with AKI showed significantly lower Hb levels and higher urinary mtDNAcn at admission. Multivariate logistic regression analysis identified low Hb and elevated urinary mtDNAcn as independent predictors of AKI. The optimal cutoff value was 10.95 g/dL for Hb and 738.0 copies/μL for urinary mtDNAcn. However, no significant temporal differences in serum mtDNAcn were observed between the AKI and no-AKI groups. Conclusions: Both Hb and urinary mtDNAcn may serve as independent biomarkers for early identification of AKI in patients with trauma. Future studies are warranted to determine optimal targets and validate these findings in larger multicenter cohorts. Full article

Background/Objectives: Cord blood mitochondrial DNA copy number (mtDNAcn) has been proposed as a biomarker reflecting environmental influences during fetal life, with reported associations with perinatal outcomes such as birth weight and length. Within the framework of the Developmental Origins of Health and Disease (DOHaD) theory, this study aimed to investigate whether cord blood mtDNAcn is related to postnatal physical growth in early childhood. Methods: We analyzed data from 150 newborns (68 females and 82 males) enrolled in the Tohoku Medical Megabank Birth and Three-Generation Cohort Study in Japan. Cord blood mtDNAcn was quantified using real-time PCR, and standard deviation scores for weight and height were assessed at 1, 2–3, 4–6, 18–24, and 36–48 months of age. Correlation analyses were conducted separately by sex. Results: Cord blood mtDNAcn showed no significant associations with body weight or height at any of the postnatal time points up to 48 months of age. Growth trajectories of infants with higher or lower mtDNAcn values at birth tended to converge toward the population mean during infancy and toddlerhood. Conclusions: Although no significant relationships were observed, this exploratory, hypothesis-generating study provides a foundation for future investigations. Larger cohorts with extended follow-up are needed to clarify the potential significance of cord blood mtDNAcn in early-life research on child growth and health. Full article

This study investigated the effects of high (atmospheric) and low (5% O₂) oxygen tension, as well as a combination of the two, on oocyte metabolism and quality during maturation. Cumulus cell–oocyte complexes collected from gilt ovaries were used for in vitro maturation. In addition, RNA-seq was conducted on the cumulus cells. Low oxygen tension throughout oocyte maturation did not alter the developmental rate to the blastocyst stage; however, it increased oocyte ATP and lipid content while reducing mitochondrial reactive oxygen species and mitochondrial membrane potential. Low-oxygen conditions increased glucose consumption but reduced mitochondrial DNA copy number and mitochondrial protein in cumulus cells. RNA-seq of cumulus cells revealed that low oxygen tension reduced mitochondrial activity and increased glycolysis, with the upregulation of glycolytic genes and downregulation of oxidative phosphorylation and steroidogenesis-related genes. In addition, a two-step oxygen protocol with low (5%) for the first period (0–21 h) and high (20%) for the last half period (21–44 h) increased the ATP and lipid content in oocytes and improved the embryonic developmental ability of the oocytes compared to the high-oxygen group. In conclusion, low oxygen tension during the first part of the maturation period is beneficial for oocyte quality, considering the observed metabolic changes. Full article

Gemykibivirus, an emerging single-stranded DNA (ssDNA) virus of the recently established genus in the family of Genomoviridae, had been discovered in human blood and cerebrospinal fluid and a variety of other body fluids. However, the molecular mechanisms of gemykibivirus entrance into the host cells and its pathogenicity remain poorly understood. To investigate the host response of gemykibivirus, we used an infectious clone of gemykibivirus previously established through molecular biology techniques to rescue virus in HEK293T cells and analyzed the changes in the host transcriptome during the infection period by RNA-Seq. Our findings indicate that gemykibivirus can both express viral proteins and accomplish replication, and high-throughput transcriptome analysis identified a total 1732 significantly different genes. Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for differentially expressed genes (DEGs) showed gemykibivirus involving several important pathways, including MAPK signaling pathway, Chemical carcinogenesis-reactive oxygen species and Oxidative phosphorylation. Interestingly, mitochondrial DNA-encoded mRNAs exhibited varying levels of upregulation, suggesting that gemykibivirus may be involved in mitochondrial fission and the regulation of mitochondrial function. Subsequently, a series of experiments proved that gemykibivirus can lead an increase in mitochondrial DNA copy number, promote the release of mtDNA into the cytoplasm, enhance reactive oxygen species production and trigger other cellular antiviral responses. Overall, we lay a foundation for revealing the relationship between Gemykibivirus and human diseases through mitochondrial functional alterations. Full article

Cardiovascular diseases hinge on a vicious, self-amplifying cycle in which mitochondrial deoxyribonucleic acid (mtDNA) dysfunction undermines cardiac bioenergetics and unleashes sterile inflammation. The heart’s reliance on oxidative phosphorylation (OXPHOS) makes it exquisitely sensitive to mtDNA insults—mutations, oxidative lesions, copy-number shifts, or aberrant methylation—that impair ATP production, elevate reactive oxygen species (ROS), and further damage the mitochondrial genome. Damaged mtDNA fragments then escape into the cytosol, where they aberrantly engage cGAS–STING, TLR9, and NLRP3 pathways, driving cytokine storms, pyroptosis, and tissue injury. We propose that this cycle represents an almost unifying pathogenic mechanism in a spectrum of mtDNA-driven cardiovascular disorders. In this review, we aim to synthesize the pathophysiological roles of mtDNA in this cycle and its implications for cardiovascular diseases. Furthermore, we seek to evaluate preclinical and clinical strategies aimed at interrupting this cycle—bolstering mtDNA repair and copy-number maintenance, reversing pathogenic methylation, and blocking mtDNA-triggered innate immune activation—and discuss critical gaps that must be bridged to translate these approaches into precision mitochondrial genome medicine for cardiovascular disease. Full article

Age-related mitochondrial dysfunction is involved in the progressive loss of mass and strength of skeletal muscle with aging. The effects of a short-term calorie restriction (ST-CR) were assessed in the oxidative skeletal soleus muscle (Sol) from 27-month-old rats and compared with those of a CR in combination with resveratrol (RSV) (ST-CR + RSV). PGC-1α and PRXIII proteins showed a marked decrease in both ST-CR and ST-CR + RSV rats. The SIRT3 protein presented a very relevant increase in both ST groups. ST-CR and ST-CR + RSV elicited a marked increase in SOD2 protein amount and activity. ST-CR and ST-CR + RSV led to recovery of the SIRT3-SOD2 axis as a fast/early response. ST-CR and ST-CR + RSV did not affect the MFN2 protein, whereas both treatments induced a relevant increase in DRP1 protein. ST-CR and ST-CR + RSV induced a decrease in Parkin protein, suggestive of rescued mitophagy, leading to the elimination of dysfunctional mitochondria. Such a response likely enhanced the fission-mediated elimination of mitochondria, supported by the marked increase in DRP1. MtDNA copy number and TFAM protein were not changed by any ST treatment. The mtDNA oxidative damage level was strongly increased by both ST treatments. All the effects elicited by ST-CR and ST-CR + RSV were specific to the oxidative type fibers. Full article

Colletotrichum spp. are the causative agents of anthracnose of rubber trees, one of the most destructive diseases, resulting in substantial economic losses. To investigate the evolutionary characteristics of these pathogenic species, we first assembled the complete mitogenomes of four dominant pathogens, i.e., C. siamense, C. fructicola, C. wanningense and C. bannaense. Comparative analyses revealed that variations in their mitogenome size were primarily driven by intron expansion and expansion/contraction within the cox1, cob and nad genes. Moreover, we observed the strong conservation of gene content, mitochondrial DNA copy number, gene order and intron features within species complexes, but a clear divergence between them. Notably, further studies indicated that patterns such as genomic organization, selective pressures and codon usage were consistent across the genus, suggesting that Colletotrichum species complexes had followed distinct evolutionary trajectories, particularly in the arrangement of protein-coding genes. Therefore, this study systematically characterized the mitogenomes of the four major Colletotrichum species associated with rubber tree anthracnose and provided novel insights into the broad evolutionary mechanisms shaping Colletotrichum species complexes. Full article

Background: Mitochondria are essential for fetal development, regulating energy metabolism and metabolic programming. This study examined how maternal nutrition and one-carbon metabolite (OCM) supplementation during early gestation affect mitochondrial function in fetal liver and muscle at day 161 of gestation in beef heifers. Methods: Twenty-nine crossbred Angus heifers were assigned to one of four treatments in a 2 × 2 factorial design: control (CON; 0.45 kg/day ADG) or restricted gain (RES; −0.23 kg/day), with or without OCM supplementation. Treatments were applied from breeding to day 63 of gestation, after which all heifers received a common diet. Fetal liver and muscle tissues were collected at day 161. Mitochondrial respiration (Seahorse assay), mtDNA copy number (qPCR), and mitochondria-related gene expression (RNA-seq) were assessed. Results: In fetal liver, state 3 respiration was highest in CON + OCM, while state 4o respiration was lowest in RES + OCM (p ≤ 0.05). mtDNA copy number was greater in RES and +OCM groups. In fetal muscle, mtDNA copy number was influenced by gain, but respiration was unaffected. Transcriptomic analysis revealed more mitochondria-related differentially expressed genes (mtDEGs) in fetal muscle than liver (90% versus 10% of total mtDEG), with most genes downregulated in the RES and +OCM groups compared to the CON and −OCM groups (FDR ≤ 0.10). Conclusions: OCM supplementation enhanced mitochondrial respiration and biogenesis in fetal liver, likely via post-translational mechanisms. In contrast, fetal muscle showed downregulation of mitochondria-related genes without functional changes, indicating transcriptional reprogramming with potential effects on later metabolic function. These results underscore early gestation as a critical window for OCM-based nutritional interventions to improve metabolic outcomes in livestock. Full article

Male fertility has declined over the years, partly due to metabolic disorders such as obesity and Type 2 diabetes. Antidiabetic drugs, including GLP-1 receptor agonists like liraglutide, are widely used to manage these conditions and aid in weight loss. Within the male reproductive tract, Leydig cells (LCs) are essential since they produce testosterone. Notably, the influence of antidiabetics on LCs remains a subject of limited investigation. Herein, we aimed to evaluate the effect of liraglutide on the physiology of LCs. To this end, we cultured LCs (BLTK1 cell line) without (control) or in the presence of selected concentrations of liraglutide. We then assessed their metabolic viability, cell proliferation, LDH release, ROS production, mitochondrial membrane potential, and in vivo mitochondrial cell performance, as well as the number of mtDNA copies. We also measured androstenedione production. Our results showed that liraglutide at pharmacological and supra-pharmacological concentrations increased the metabolic viability of LCs and reduced ROS production at all concentrations. Furthermore, the pharmacological concentration of liraglutide increased the basal respiration, maximal respiration, proton leak, and oxygen consumption rate related to ATP-linked production. Androstenedione production remained unchanged, which may be related to the inherent limitations of the cell line in supporting steroidogenesis. Overall, our findings suggest that liraglutide exhibits a potential protective effect on LC function, particularly by enhancing metabolic viability, reducing oxidative stress, and improving mitochondrial performance, highlighting its potential beyond the established role in diabetes and weight management. Full article

Mitochondria perform critical roles in cellular functions, particularly in metabolism and cell death regulation. Mutations in nuclear and mitochondrial genes can cause mitochondrial dysfunction, leading to classical mitochondrial diseases. Emerging evidence suggests that mitochondrial adaptations in cancer support the high energy demands of proliferating cells and contribute to tumor progression through anti-apoptotic mechanisms, dysregulated mitochondrial quality control (mtQC), and altered mitochondrial DNA (mtDNA) copy numbers. Interestingly, several mitochondrial pathways involved in cancer progression resemble those implicated in mitochondrial diseases. From this perspective, although cancer is not a classical mitochondrial disease, its progression involves mitochondria-associated pathways similar to those in mitochondrial disorders, suggesting that cancer may be considered a mitochondria-related disease in a broader sense. Understanding these shared mechanisms could provide new insights into precision treatment strategies. Furthermore, mitochondrial dysfunction is increasingly recognized in precancerous conditions, suggesting its potential as a target for early intervention. Oral potentially malignant disorders (OPMDs) serve as a valuable model for studying these mitochondria-associated mechanisms, offering a promising avenue for both therapeutic advancements and preventive approaches. Full article

Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial–mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria. Full article

Insulin resistance is a fundamental pathophysiological mechanism contributing to the development of type 2 diabetes and metabolic syndrome. Recently, attention has focused on mitochondria’s role in glucose and lipid metabolism. Mitochondrial dysfunction is strongly associated with impaired energy metabolism and elevated oxidative stress. We investigated the mitochondrial DNA (mtDNA) copy number in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in insulin-sensitive (IS) and insulin-resistant (IR) individuals. Twenty-seven paired adipose tissue biopsies were obtained during elective abdominal surgery. DNA and RNA were extracted, and mtDNA copy number was quantified using Real-Time PCR. We found that mtDNA content in VAT was approximately two-fold lower than in SAT. Furthermore, in IR individuals, mtDNA copy number was significantly reduced in both SAT and VAT compared to IS subjects. A strong positive correlation was observed between mtDNA content in VAT and body mass index (BMI), and a negative correlation was found with the QUICKI index. Additionally, mtDNA copy number in VAT positively correlated with the expression of several genes involved in insulin signalling, lipid metabolism, and other metabolic pathways. These findings underscore the central role of mitochondrial function in VAT in the context of metabolic disorders and suggest that targeting mitochondrial regulation in this tissue may represent a promising therapeutic approach. Full article

In this study, we investigated the mitochondrial defects resulting from the deletion of GCN5, a lysine-acetyltransferase, in the yeast Saccharomyces cerevisiae. Gcn5 serves as the catalytic subunit of the SAGA acetylation complex and functions as an epigenetic regulator, primarily acetylating N-terminal lysine residues on histones H2B and H3 to modulate gene expression. The loss of GCN5 leads to mitochondrial abnormalities, including defects in mitochondrial morphology, a reduced mitochondrial DNA copy number, and defective mitochondrial inheritance due to the depolarization of actin filaments. These defects collectively trigger the activation of the mitophagy pathway. Interestingly, deleting CSN5, which encodes to Csn5/Rri1 (Csn5), the catalytic subunit of the COP9 signalosome complex, rescues the mitochondrial phenotypes observed in the gcn5Δ strain. Furthermore, these defects are suppressed by exogenous ergosterol supplementation, suggesting a link between the rescue effect mediated by CSN5 deletion and the regulatory role of Csn5 in the ergosterol biosynthetic pathway. Full article