Search Results (383)

Background/Objectives: Mitochondrial DNA (mtDNA) variations are linked to psychiatric disorders, but their association with internet gaming addiction (IGA) remains unexplored. We investigated mitochondrial D-loop D310 and D514 regions and mtDNA copy number (mtCN) in male adolescents with and without IGA, exploring their associations with leukocyte telomere length (LTL). Methods: Questionnaires assessed IGA in 206 male adolescents. Blood samples were analyzed for (C)_n repeats at D310 and (CA)_n repeats at D514. Relative mtCN and LTL were measured using quantitative PCR. Results: D310 polymorphism distribution differed significantly between the IGA and non-IGA groups (p = 0.040). Among the (C)_n repeats, (C)₈ frequency at D310 was significantly lower in the IGA group than in the non-IGA group (p = 0.017). Multivariable logistic regression initially identified the (C)₈ polymorphism as an independent predictor reducing IGA likelihood (OR = 0.474, p = 0.014), although this nominal association did not remain statistically significant after formal Bonferroni correction. mtCN differences were not significant (p = 0.247). Notably, LTL was significantly shorter in the IGA group among carriers of (C)₈ and (CA)₅ polymorphisms (both p = 0.001). Multivariable linear regression confirmed that IGA remained robustly associated with shorter LTL (B = −40.180, p < 0.001), while (C)₈ and (CA)₅ repeats were not independently associated with LTL shortening. Conclusions: While the (C)₈ polymorphism’s direct genetic contribution to IGA susceptibility remains preliminary and hypothesis-generating due to multiple testing attenuation, IGA exhibits a robust, independent association with LTL shortening. Mitochondrial genomic backgrounds may play a subtle, modulatory role in behavioral addiction pathways, warranting further longitudinal validation. Full article

Primary mitochondrial diseases (PMDs) are one of the most common genetic disorders with an estimated prevalence of 1 in 4300. This review article summarises the latest updates in the field of mitochondrial medicine over the last decade. The availability of exome and genome sequencing in clinical practice has empowered clinicians to unravel the phenotypic heterogeneity of PMD and to end the diagnostic odyssey experienced by many patients and families. In unresolved cases, the detection of variant(s) of unknown significance by next-generation sequencing creates diagnostic and clinical uncertainties, and integrating a multi-omics approach can improve diagnostic yield. Alongside breakthroughs in genomic technologies, there is growing interest in using fluid biomarkers to guide diagnosis, monitor disease progression, and potentially serve as clinical trial endpoints. However, the clinical application of these fluid biomarkers in unselected patient cohorts with different disease onset and phenotypes would require more robust evidence. Natural history studies derived from national and international collaborations have provided insights into genotype–phenotype relationships and prognostic factors across several genotypes, including m.3243A>G, MT-ATP6, POLG, and TK2. Advances in therapeutic discoveries and clinical trials are challenging the obsolete dogma that PMDs are untreatable and bringing hope to patients; four compounds have been licensed, and many trials are in progress. Many barriers and challenges to translating laboratory discoveries into clinical therapy in PMD remain, including preclinical models for efficacy and safety testing, sample size, trial design, and the selection of outcome measures and trial endpoints. Full article

Mitochondrial codon usage and selective pressures drive adaptive evolution and translation efficiency. This study provides insights into the evolutionary constraints shaping 13 core mitochondrial proteins in Corvides, based on 117 species, including 51 newly assembled genomes. We present evidence linking codon-level sequence architecture, protein structure, and selective pressures. These protein-coding genes (PCGs) are under strong purifying selection, with dN/dS ratios ranging from 0.00779 (MT-CO1) to 0.16214 (MT-ATP8). This conservation is reflected in the 3D model of MT-CO1, where conserved residues cluster within 12 transmembrane helices forming the core of its proton-pumping function. At the sequence level, we identify signatures of selection for translational efficiency, which are critical for accurate synthesis and folding. These signatures include a significant preference for “optimal” codons that perfectly match tRNA anticodons (p < 0.001). We also find lineage-specific features such as codon aversion motifs (CAMs). The MT-ATP6 gene exhibits complete aversion of the CGA codon in Oriolus chinensis and of the ACT codon in O. kundoo. These sequence-level features resolve the deep phylogenetic relationships within the group, demonstrating the effectiveness of our multi-layered analytical framework. Overall, our results link codon-level sequence architecture with protein structural constraints, functional evolutionary signals, and mitochondrial genome evolution in Corvides. Full article

Mitochondrial DNA (mtDNA) mutations are associated with a diverse spectrum of diseases and pose a significant threat to human health. Despite their importance as therapeutic targets, the unique structural and electrochemical properties of mitochondria—most notably the impermeable inner mitochondrial membrane and the high membrane potential—present formidable challenges for the targeted delivery of therapeutic agents. Currently, there are no approved curative treatments for patients harboring pathogenic mtDNA mutations. In this review, we discuss recent advancements in gene therapy for mitochondrial genome-related disorders, with a particular focus on allotopic expression of mtDNA-encoded genes and mitochondrial genome editing technologies. We conclude that allotopic expression currently stands as the most promising approach for near-term clinical implementation. But we also pay great attention to programmable nucleases and base editors utilizing RNA-independent DNA recognition which are evolving with remarkable speed. Full article

Mitochondrial dysfunction has been increasingly implicated in the pathobiology of neurodevelopmental conditions, particularly autism and attention-deficit/hyperactivity disorder (ADHD). Because the developing brain is critically dependent on sustained ATP production, impairments in oxidative phosphorylation, mitochondrial dynamics, and redox balance may disrupt neuronal maturation, synaptic development, and neural circuit refinement during sensitive developmental periods. This review examines evidence from postmortem neurochemistry, genomics, magnetic resonance spectroscopy, and biomarker research to characterize mitochondrial impairment across autism and ADHD. Studies in autism report an elevated burden of heteroplasmic mitochondrial DNA (mtDNA) variants, along with alterations in mtDNA copy number, respiratory chain capacity, fission–fusion dynamics, and antioxidant defenses. Postmortem data demonstrate reduced activity of electron transport chain Complexes I, III, and V in the frontal cortex, temporal lobe, and cerebellum. These bioenergetic abnormalities are accompanied by elevated oxidative stress markers alongside mitochondria-mediated immune activation. In vivo neuroimaging corroborates these findings through elevated cerebral lactate and reduced phosphocreatine-to-ATP ratios. Evidence in ADHD is limited, but similarly implicates mitochondrial dysfunction, consistent with the frequent co-occurrence of these conditions and their partially shared architecture. The available literature supports mitochondrial dysfunction as a transdiagnostic biological feature of neurodevelopmental conditions, with relevance to mechanistic biomarker identification and targeted therapeutic development. Full article

Corydalis ophiocarpa is a medicinally valuable plant, noted for its abundant alkaloid content. Despite its significance, the mitochondrial (mt) genome of this plant has not been characterized, which impedes both the phylogenetic understanding within the Corydalis genus and the comprehension of its full genetic potential. In this research, we successfully assembled the complete mitogenome of C. ophiocarpa by employing a hybrid method that integrates Oxford Nanopore long reads with Illumina short reads. The assembled genome forms a circular structure of 600,064 bp, with a GC content of 46.49%, and includes 63 genes, comprising 40 unique protein-coding genes (PCGs), 20 tRNAs, and three rRNAs. Through assembly and coverage analysis, we identified a 6383 bp forward repeat associated with a contig having approximately double the depth, indicating a repeat-mediated multipartite structure where the main circle may coexist with two smaller subgenomic forms. We discovered 775 C-to-U RNA editing sites across the 40 PCGs, with 95.4% being non-synonymous and favoring hydrophobic amino acid substitutions, particularly in Complex I subunits. Furthermore, we identified sixteen mt plastid DNA fragments constituting 2.43% of the mitogenome, a proportion more than double that found in the closely related C. saxicola. Phylogenetic analysis confirms that C. ophiocarpa is most closely related to C. saxicola, with C. pauciovulata as another close relative. This study presents the first complete mitogenome of C. ophiocarpa, providing a genomic basis for investigating the relationships between mt genome structure, post-transcriptional regulation, and specialized metabolism in the Corydalis genus. Full article

The systematics of white-tailed deer (Odocoileus virginianus) has been controversial. Some mammalogists consider the white-tailed deer to be a single species, whereas others consider it to consist of multiple species. To help resolve the controversy, we sequenced mitochondrial cytochrome B (mtCyt-b) in samples collected from 83 Neotropical white-tailed deer. Furthermore, we analyzed mitogenomes of samples collected from 19 white-tailed deer. There were five main results, as follows: (1) Phylogenetic analyses with the mtCyt-b dataset showed the existence of eight groups of O. virginianus, three in North and Central America and five in South America. It was hypothesized from different analyses that a Central American O. virginianus population generated the white-tailed deer populations in South America. (2) The haplotype temporal diversification within O. virginianus occurred during the Pleistocene. With the mitogenome dataset, it was dated to have occurred approximately 2.2 mya, using both Bayesian inference and haplotype networks. (3) All of these O. virginianus groups showed elevated levels of mitochondrial genetic diversity for the mtCyt-b dataset, with the exception of the Ecuadorian population (4) Some groups of O. virginianus yielded significant evidence of female population expansions with the mtCyt-b dataset. (5) Although the genetic heterogeneity among these O. virginianus groups was significant, the genetic distances were relatively small. Provisionally, the karyotypic differences between North American and Colombian specimens were very small; therefore, until further karyotypic studies demonstrate otherwise, we consider the existence of a single species of O. virginianus. Because mtDNA genomes have only one quarter of the effective number of autosomal nuclear genes, this generates relatively rapid coalescence times, which can inflate estimates of divergence among populations. Therefore, it is very important to soon sequence the nuclear genes for the different geographic assemblages of O. virginianus found. Full article

Background: The transfer of a nucleus from one oocyte to another offers patients harbouring high levels of mitochondrial DNA mutation and sufferers of frequent fertilisation failure or early embryonic arrest the potential to have healthy children. However, a small amount of mtDNA is carried over with the nucleus as the transfer takes place. Consequently, we still need to distinguish between the effects of the carryover and the transfer of a nucleus itself from a mature oocyte. Methods: To overcome this, we analysed a series of hatching stage blastocysts generated using metaphase II spindle transfer and mitochondrial supplementation. The latter approach also introduces a small amount of mtDNA into the oocyte as fertilisation takes place. For both manipulations, an autologous approach was used to overcome the effects of third-party transfer. Results: We then compared the changes in global gene expression between the two groups. We found that the nuclear transfer process affected a number of gene networks and pathways. These included metabolic, cell cycle, inflammatory and immune, and epigenetic responses. A comparison with earlier stage blastocysts did not suggest that the cause was due to developmental delay. Conclusions: Critically, these changes could affect offspring health and well-being as is the case following somatic cell nuclear transfer. Full article

The field of mitoepigenetics involves the investigation of modifications in mitochondrial DNA (mtDNA), genomic DNA that encodes mitochondrial proteins, and the expression of RNAs that regulate mitochondrial gene expression but do not alter the DNA sequence. This area of research is growing rapidly and has substantial relevance to male mammalian fertility. Among the known mitoepigenetic mechanisms, mitochondrial microRNAs (mitomiRs) have attracted substantial attention due to their potential roles in modulating mitochondrial gene expression in response to environmental stressors. Since many problems with male fertility are known to result from environmental factors, there has been increasing interest in studying epigenetic mechanisms that contribute to male reproductive function. This review explores the current literature regarding different mitoepigenetic mechanisms and their implications for male mammalian fertility, focusing primarily on the known and potential involvement of mitomiRs in model species and humans. Understanding mitoepigenetics may contribute to the development of non-invasive diagnostic biomarkers and individualized therapeutic approaches to male infertility due to their stability in body fluids, tissue specificity, and sensitivity to disease states. Full article

Horizontal Gene Transfer (HGT) is a hallmark of the evolution of parasitic plants, facilitated by the haustorial connection. While mitochondrial HGT is widespread, the extent of nuclear HGT and the long-term retention of foreign genetic material in holoparasitic lineages remain poorly understood. This study explores the genomic architecture of Prosopanche americana (Hydnoraceae), a non-photosynthetic holoparasite currently specialized on Fabaceae. Through a comparative phylogenomic approach integrating draft mitochondrial genomes (mtDNA) and nuclear transcriptomes of P. americana, we identified a multi-layered landscape of foreign DNA. The mtDNA of P. americana contains 18 foreign regions (>500 bp) primarily derived from Solanales, Malvales, and Fabales. Notably, 13 of these regions are shared with P. panguanensis, indicating they were acquired in their common ancestor before speciation and ecological shift. In the nuclear genome, we identified 303 horizontally acquired transcripts (99 orthogroups) with high confidence. Functional analysis revealed an enrichment of foreign genes involved in metabolic pathways and plastid functions (e.g., photosystems and thylakoids) exclusively derived from the ancestral host order Solanales. Our results demonstrate that the genome of P. americana acts as a “molecular fossil,” preserving evidence of past ecological interactions with diverse host lineages. The disparity in HGT footprints between the current host (Fabaceae) and ancestral hosts suggests a period of high genomic plasticity followed by host specialization, providing new insights into the timing and dynamics of horizontal gene flow in holoparasitic Piperales. Full article

Ultraviolet (UV) radiation from the sun causes adverse skin changes such as premature aging. UV-induced mitochondrial DNA (mtDNA) alterations, including deletions, contribute to photoaging and cellular dysfunction. While the most frequent mtDNA rearrangement is the common deletion (CD), characterized by the loss of nearly one-third of the genome (4977 bp), detailed knowledge of mechanisms governing UV-mediated initiation of the CD and mitigation strategies are lacking. Here, we investigated how increasing UV exposure increases CD levels in human skin fibroblasts via cellular reactive oxygen species (ROS) formation and mtDNA oxidation and demonstrated that antioxidant preconditioning of cells prevents UVA-induced CD accumulation. Conversely, UVB exposure induced cyclobutane pyrimidine dimers (CPDs) without affecting ROS, suggesting an ROS-independent pathway. Using a 3D full-thickness human skin model, we confirmed UVA-dependent CD formation in both the epidermis and dermis. RNA-Seq analysis of UVA-exposed fibroblasts revealed upregulation of mitochondrial DNA replication genes and downregulation of mtDNA repair genes. These findings provide insight into how UVA and UVB differ in detrimental effects on mtDNA, with UVA impacting mtDNA maintenance and transcription via a ROS-dependent mechanism, and provide a physiologically relevant platform to evaluate potential interventions. Full article

Wildlife trafficking poses a severe threat to global biodiversity and ecosystem stability, necessitating robust forensic tools for tracing the origins of illegally traded taxa. In this study, we developed a method of single-nucleotide polymorphism (SNP)-based molecular markers to enable precise geographical traceability of four animal species native to China: the Tibetan macaque (Macaca thibetana), brown eared pheasant (Crossoptilon mantchuricum), blue eared pheasant (Crossoptilon auritum), and Chinese pangolin (Manis pentadactyla). We studied these four species because their DNA is characterized by distinct population genetic structure, they are subjected to illegal trafficking, and given their diverse evolutionary histories, this allowed us to assess the general applicability of our forensic genetic framework in reducing wildlife crime. Based on whole-genome resequencing data from 26 Tibetan macaques, 51 eared pheasants and 42 Chinese pangolins, we performed population genetic analyses to elucidate their genetic structure and identify population-specific loci. The results indicated that all samples from these four species showed clear genetic differentiation and distinct clustering, allowing us to design primers to facilitate PCR-based traceability. We also assessed the utility of mitochondrial DNA (mtDNA) for tracing Tibetan macaques and both species of eared pheasants. We found that traceability accuracy using mtDNA was lower than when using SNPs. Our research offers a SNP-based traceability framework that accurately determines the geographical origin of wildlife samples to the genetic population level, and this provides a powerful tool for combating illegal trade and aiding conservation efforts. Full article

During eukaryotes evolution, mitochondrial DNA (mtDNA) fragments integrate into nuclear genomes, forming nuclear mitochondrial DNA sequences (Numts). Tortricidae (Lepidoptera), a species-rich and economically critical family, lacks systematic characterization of Numts, which hinders reliable molecular research. Here, we systematically characterized Numts in 27 Tortricidae species spanning two subfamilies via genome download, mitochondrial genome annotation, and Numt identification and characterization. With each species’ mtDNA as query, Numt identification was performed with an E-value threshold of 10⁻⁴ and a sequence similarity cut-off of >60%, with a minimum length of 50 bp to exclude spurious hits. Results showed that all species contained Numts, with copy numbers varying drastically (9–208). Numt numbers positively correlated with nuclear genome length, but not mitochondrial genome length. Numts insertion flanking regions had significantly higher AT content than nuclear genome, indicating the insertion preference for AT-rich regions. Numts were predominantly derived from the mitochondrial cox1 gene, highlighting the risk of co-amplification when cox1 is used as a DNA barcode for species identification or phylogenetic studies. This study represents a systematic charaterizition of copy number, length distribution, insertion sequence preferences, and mitochondrial gene origins of Numts in Tortricidae, offering valuable references for refining molecular systematics, comparative genomics, and pest management in Tortricidae and related lepidopteran groups. Full article

Background/Objectives: Mitochondrial DNA (mtDNA) is an important resource for understanding human ancestry, population diversity, and the molecular mechanisms of mitochondrial diseases. However, analyzing mtDNA thoroughly often requires advanced bioinformatics skills and command-line knowledge. To address this challenge, we created Mitochondrial Genome Explorer (MitoGEx), a user-friendly computational pipeline optimized for human mtDNA analysis that combines multiple mtDNA analysis modules within a single graphical user interface. Methods: The platform simplifies key analytical steps, such as quality control, sequence alignment, alignment quality assessment, variant detection, haplogroup classification, and phylogenetic reconstruction. Users can choose between Quick and Advanced modes, which offer default settings or customizable options based on their analysis needs. To demonstrate its effectiveness, we analyzed 15 whole-exome sequencing (WES) samples from Songklanagarind Hospital using MitoGEx. Results: The sequencing data were of high quality, with over 92 percent of bases scoring above a Phred score and consistent GC content across all samples. Variant detection using the GATK mitochondrial pipeline and annotation with ANNOVAR and the MitImpact database revealed multiple high-confidence variants. Haplogroup classification with Haplogrep 3 and phylogenetic analysis with IQ-TREE 2 confirmed diverse maternal lineages within the cohort. Conclusions: Taken together, MitoGEx facilitates mitochondrial genome analysis in a reproducible and accessible manner for both research and clinical bioinformatics applications. The analytical results produced by MitoGEx are concordant with those obtained using standalone bioinformatic tools, demonstrating analytical correctness. By integrating all analysis steps into a single automated workflow, MitoGEx reduces execution time and limits human error inherent to manual, multi-step pipelines. Full article

Background/Objectives: Mitochondrial DNA (mtDNA) analysis is an essential tool for human identification in contexts such as disaster victim identification (DVI) and missing persons cases, where the remains may be highly degraded or even skeletonised. Traditionally, capillary electrophoresis (CE)-based Sanger sequencing has been the standard method for analysing the mtDNA control region. With the development of massively parallel sequencing (MPS) technologies, mtDNA sequencing using MPS offers advantages over traditional Sanger sequencing, such as increased sensitivity, higher throughput, and less sample consumption. The Ion Chef™ and Ion S5™ XL system from Thermo Fisher Scientific represents one such MPS system. Methods: We conducted an internal validation study evaluating key parameters including (a) concordance, repeatability and reproducibility; (b) potential cross-contamination; (c) sensitivity; (d) effects of library pooling on read depth; and (e) mixture sample analysis. Additionally, to mimic samples typically encountered during forensic investigations, case type samples were also used to evaluate the performance of this workflow. While the entire mitochondrial genome was sequenced in this validation study, considering that the international guidelines for full mtDNA genome analysis and interpretation have yet to be fully updated, our analysis, interpretation and subsequent implementation are limited to the control region only. Results: The results obtained demonstrated the reliability, sensitivity and reproducibility of this MPS workflow. Conclusions: This internal validation study supports the implementation of this workflow in our laboratory for the analysis of forensic casework samples. Full article