Mitochondrial DNA Research Articles

Oxidative stress induces release of mitochondrial DNA into the extracellular space in human placental villous trophoblast BeWo cells.

Circulating cell-free mitochondrial DNA (ccf-mtDNA) is an indicator of cell death, inflammation, and oxidative stress. ccf-mtDNA differs in pregnancies with placental dysfunction from healthy pregnancies and the direction of this difference depends on gestational age and method of mtDNA quantification. Reactive oxygen species (ROS) trigger release of mtDNA from non-placental cells; yet it is unknown whether trophoblast cells release mtDNA in response to oxidative stress, a common feature of pregnancies with placental pathology. We hypothesized that oxidative stress would induce cell death and release of mtDNA from trophoblast cells. BeWo cells were treated with antimycin A (10-320 mM) or rotenone (0.2-50 mM) to induce oxidative stress. A multiplex real-time quantitative PCR (qPCR) assay was used to quantify mtDNA and nuclear DNA in membrane bound, non-membrane bound, and vesicular-bound forms in cell culture supernatants and cell lysates. Treatment with antimycin A increased ROS (p<0.0001), induced cell necrosis (p=0.0004) but not apoptosis (p=0.6471) and was positively associated with release of membrane-bound and non-membrane bound mtDNA (p<0.0001). Antimycin A increased mtDNA content in exosome-like extracellular vesicles (vesicular-bound form; p=0.0019) and reduced autophagy marker expression (LC3A/B, p=0.0002; p62, p<0.001). Rotenone treatment did not influence mtDNA release or cell death (p>0.05). Oxidative stress induces release of mtDNA into the extracellular space and causes non-apoptotic cell death and a reduction in autophagy markers in BeWo cells, an established in vitro model of human trophoblast cells. Intersection between autophagy and necrosis may mediate the release of mtDNA from the placenta in pregnancies exposed to oxidative stress.

A DNA barcode reference library of Croatian mosquitoes (Diptera: Culicidae): implications for identification and delimitation of species, with notes on the distribution of potential vector species

BackgroundMosquitoes pose a risk to human health worldwide, and correct species identification and detection of cryptic species are the most important keys for surveillance and control of mosquito vectors. In addition to traditional identification based on morphology, DNA barcoding has recently been widely used as a complementary tool for reliable identification of mosquito species. The main objective of this study was to create a reference DNA barcode library for the Croatian mosquito fauna, which should contribute to more accurate and faster identification of species, including cryptic species, and recognition of relevant vector species.MethodsSampling was carried out in three biogeographical regions of Croatia over six years (2017–2022). The mosquitoes were morphologically identified; molecular identification was based on the standard barcoding region of the mitochondrial COI gene and the nuclear ITS2 region, the latter to identify species within the Anopheles maculipennis complex. The BIN-RESL algorithm assigned the COI sequences to the corresponding BINs (Barcode Index Number clusters) in BOLD, i.e. to putative MOTUs (Molecular Operational Taxonomic Units). The bPTP and ASAP species delimitation methods were applied to the genus datasets in order to verify/confirm the assignment of specimens to specific MOTUs.ResultsA total of 405 mosquito specimens belonging to six genera and 30 morphospecies were collected and processed. Species delimitation methods assigned the samples to 31 (BIN-RESL), 30 (bPTP) and 28 (ASAP) MOTUs, with most delimited MOTUs matching the morphological identification. Some species of the genera Culex, Aedes and Anopheles were assigned to the same MOTUs, especially species that are difficult to distinguish morphologically and/or represent species complexes. In total, COI barcode sequences for 34 mosquito species and ITS2 sequences for three species of the genus Anopheles were added to the mosquito sequence database for Croatia, including one individual from the Intrudens Group, which represents a new record for the Croatian mosquito fauna.ConclusionWe present the results of the first comprehensive study combining morphological and molecular identification of most mosquito species present in Croatia, including several invasive and vector species. With the exception of some closely related species, this study confirmed that DNA barcoding based on COI provides a reliable basis for the identification of mosquito species in Croatia.Graphical

Distribution and genetic diversity of cobitid species in Iran (Teleostei: Cobitidae)

Several species of Cobitis have been reported within Iran, but only four are recognized as valid. The geographical distribution and genetic diversity of these species are not well-known. Two new populations of C. saniae and C. avicennae were reported herein based on their morphological and phylogenetic characters from the Mahabad River, a tributary of the Urmia Lake basin, and the Razavar River, a tributary of the Karkheh drainage, respectively. The genetic diversity and genetic structure of populations of C. saniae, C. avicennae, and C. faridpaki were analysed using the DNA sequences of the mitochondrial COI gene. COI sequences from various watersheds in Iran, Azerbaijan, and Georgia were used. A moderate to high level haplotype diversity and low nucleotide diversity were found in most of the populations of all three species. The AMOVA test and pairwise FST comparison revealed significant genetic structure and genetic distance between the Urmia Lake basin and other C. saniae populations. The results highlight the importance of conserving these species and their habitats, particularly in the Urmia Lake basin, where significant genetic differentiation was observed.

A novel pathogenic mitochondrial DNA variant m.4344T>C in tRNAGln causes developmental delay.

Mitochondrial diseases are a group of genetic diseases caused by mutations in mitochondrial DNA and nuclear DNA. However, the genetic spectrum of this disease is not yet complete. In this study, we identified a novel variant m.4344T>C in mitochondrial tRNAGln from a patient with developmental delay. The mutant loads of m.4344T>C were 95% and 89% in the patient's blood and oral epithelial cells, respectively. Multialignment analysis showed high evolutionary conservation of this nucleotide. TrRosettaRNA predicted that m.4344T>C variant would introduce an additional hydrogen bond and alter the conformation of the T-loop. The transmitochondrial cybrid-based study demonstrated that m.4344T>C variant impaired the steady-state level of mitochondrial tRNAGln and decreased the contents of mitochondrial OXPHOS complexes I, III, and IV, resulting in defective mitochondrial respiration, elevated mitochondrial ROS production, reduced mitochondrial membrane potential and decreased mitochondrial ATP levels. Altogether, this is the first report in patient carrying the m.4344T>C variant. Our data uncover the pathogenesis of the m.4344T>C variant and expand the genetic mutation spectrum of mitochondrial diseases, thus contributing to the clinical diagnosis of mitochondrial tRNAGln gene variants-associated mitochondrial diseases.

Individual identification method using samples associated with doping tests: A comparison of mitochondrial and nuclear genetic data.

Doping offenses involve the use or attempted use of any prohibited method or substance as well as substituting samples. Consequently, it has been recommended that short tandem repeat (STR) analysis be used to determine if the doping control samples are from the same athlete. However, it has been recognized that it may be difficult to obtain full STR analysis using negligible amounts of DNA samples. Mitochondrial DNA (mtDNA) is characterized by its stability and high cellular copy number. Therefore, mtDNA testing in urine is expected to be used to analyze samples that cannot be analyzed using STR analysis. The objective of this study was to compare mtDNA testing with STR analysis by conducting sensitivity, concordance (whole blood, dried blood spot, and urine), and case-type studies. In sensitivity studies, mtDNA testing exhibited greater sensitivity compared with STR analysis. Concordance studies indicated that all samples were consistent with the mtDNA sequences and STR profiles. Allelic dropout occurred in some urine samples that were examined for STR analysis. Case-type sample studies demonstrated that mtDNA testing could be used to obtain DNA profiles of all the samples tested, including blood, dried blood spots, urine, blood residues on needles, and blood stains. In conclusion, mtDNA testing is valuable for analyzing highly degraded DNA samples, such as urine samples, compared with STR analysis. Urine testing should be performed for the initial testing procedure, because mtDNA is inherited maternally. In situations where the DNA match is detrimental to the athlete, additional blood STR analysis may be required.

Mitochondrial DNA in bronchoalveolar lavage fluid is associated with the prognosis of idiopathic pulmonary fibrosis: a single cohort study

BackgroundExtracellular mitochondrial DNA (mtDNA) is released from damaged cells and increases in the serum and bronchoalveolar lavage fluid (BALF) of idiopathic pulmonary fibrosis (IPF) patients. While increased levels of serum mtDNA have been reported to be linked to disease progression and the future development of acute exacerbation (AE) of IPF (AE-IPF), the clinical significance of mtDNA in BALF (BALF-mtDNA) remains unclear. We investigated the relationships between BALF-mtDNA levels and other clinical variables and prognosis in IPF.MethodsExtracellular mtDNA levels in BALF samples collected from IPF patients were determined using droplet-digital PCR. Levels of extracellular nucleolar DNA in BALF (BALF-nucDNA) were also determined as a marker for simple cell collapse. Patient characteristics and survival information were retrospectively reviewed.ResultsmtDNA levels in serum and BALF did not correlate with each other. In 27 patients with paired BALF samples obtained in a stable state and at the time of AE diagnosis, BALF-mtDNA levels were significantly increased at the time of AE. Elevated BALF-mtDNA levels were associated with inflammation or disordered pulmonary function in a stable state (n = 90), while being associated with age and BALF-neutrophils at the time of AE (n = 38). BALF-mtDNA ≥ 4234.3 copies/µL in a stable state (median survival time (MST): 42.4 vs. 79.6 months, p < 0.001) and ≥ 11,194.3 copies/µL at the time of AE (MST: 2.6 vs. 20.0 months, p = 0.03) were associated with shorter survival after BALF collection, even after adjusting for other known prognostic factors. On the other hand, BALF-nucDNA showed different trends in correlation with other clinical variables and did not show any significant association with survival time.ConclusionsElevated BALF-mtDNA was associated with a poor prognosis in both IPF and AE-IPF. Of note, at the time of AE, it sharply distinguished survivors from non-survivors. Given the trends shown by analyses for BALF-nucDNA, the elevation of BALF-mtDNA might not simply reflect the impact of cell collapse. Further studies are required to explore the underlying mechanisms and clinical applications of BALF-mtDNA in IPF.

Extension of the geographical range of the primary burrowing crayfish Cambarus strigosus Hobbs, 1981 (Decapoda: Astacidea: Cambaridae) in South Carolina

Abstract Knowledge of the geographical distribution for many primary burrowing crayfishes is often limited to information presented in species descriptions or field notes associated with epigean crayfish surveys. Cambarus strigosusHobbs, 1981, a rare primary burrowing crayfish, was collected as part of a survey of the Sumter National Forest, South Carolina (SC), USA. Prior to this discovery, C. strigosus appeared to be endemic to mid-reaches of the Broad River Drainage in Georgia (GA). We conducted additional field sampling in SC and GA and used mitochondrial DNA (mtDNA) to compare the relative genetic distance between individuals across all populations in an effort to determine the identity of the specimens collected. Genetic data indicated that the crayfish collected in SC was C. strigosus, with one shared haplotype between SC and GA populations. Our genetic results exhibited geographic structuring and indicated that SC populations have a specific haplotype unique to them, providing strong evidence that SC populations are not introduced. Two additional SC records of C. strigosus from 1983 housed in the US National Museum were examined and determined to be C. strigosus. With these records, we hypothesized that like in GA, the distribution of C. strigosus in SC is limited to riparian habitats associated with the Savannah River Drainage. While the range of this species has been extended, it is still limited to small portions of this drainage. Thus, further sampling to determine the true extent of C. strigosus distribution within SC along with conservation efforts are needed to protect this globally rare species.

Mitonuclear interactions impact aerobic metabolism in hybrids and may explain mitonuclear discordance in young, naturally hybridizing bird lineages.

Understanding genetic incompatibilities and genetic introgression between incipient species are major goals in evolutionary biology. Mitochondrial genes evolve rapidly and exist in dense gene networks with coevolved nuclear genes, suggesting that mitochondrial respiration may be particularly susceptible to disruption in hybrid organisms. Mitonuclear interactions have been demonstrated to contribute to hybrid dysfunction between deeply divergent taxa crossed in the laboratory, but there are few empirical examples of mitonuclear interactions between younger lineages that naturally hybridize. Here, we use controlled hybrid crosses and high-resolution respirometry to provide the first experimental evidence in a bird that inter-lineage mitonuclear interactions impact mitochondrial aerobic metabolism. Specifically, respiration capacity of the two mitodiscordant backcrosses (with mismatched mitonuclear combinations) differs from one another, although they do not differ significantly from the parental groups or mitoconcordant backcrosses as we would expect of mitonuclear disruptions. In the wild hybrid zone between these subspecies, the mitochondrial cline centre is shifted west of the nuclear cline centre, which is consistent with the direction of our experimental results. Our results therefore demonstrate asymmetric mitonuclear interactions that impact the capacity of cellular mitochondrial respiration and may help to explain the geographic discordance between mitochondrial and nuclear genomes observed in the wild.

Reactive oxygen species-responsive supramolecular deucravacitinib self-assembly polymer micelles alleviate psoriatic skin inflammation by reducing mitochondrial oxidative stress

IntroductionThe new topical formula is urgent needed to meet clinical needs for majority mild patients with psoriasis. Deucravacitinib exerts outstanding anti-psoriatic capacity as an oral TYK2 inhibitor; however, single therapy is insufficient to target the complicated psoriatic skin, including excessive reactive oxygen species (ROS) and persistent inflammation. To address this need, engineered smart nano-therapeutics hold potential for the topical delivery of deucravacitinib.Methodshydrophobic Deucravacitinib was loaded into polyethylene glycol block-polypropylene sulphide (PEG-b-PPS) for transdermal delivery in the treatment of psoriasis. The oxidative stress model of HaCaT psoriasis was established by TNF-α and IL-17A in vitro. JC-1 assay, DCFH-DA staining and mtDNA copy number were utilized to assess mitochondrial function. 0.75% Carbopol®934 was incorporated into SPMs to produce hydrogels and Rhb was labeled to monitor penetration by Immunofluorescence. In vivo, we established IMQ-induced psoriatic model to evaluate therapeutic effect of Car@Deu@PEPS.ResultsDeu@PEPS exerted anti-psoriatic effects by restoring mitochondrial DNA copy number and mitochondrial membrane potential in HaCaT. In vivo, Car@Deu@PEPS supramolecular micelle hydrogels had longer retention time in the dermis in the IMQ-induced ROS microenvironment. Topical application of Car@Deu@PEPS significantly restored the normal epidermal architecture of psoriatic skin with abrogation of splenomegaly in the IMQ-induced psoriatic dermatitis model. Car@Deu@PEPS inhibited STAT3 signaling cascade with a corresponding decrease in the levels of the differentiation and proliferative markers Keratin 17 and Cyclin D1, respectively. Meanwhile, Car@Deu@PEPS alleviated IMQ-induced ROS generation and subsequent NLRP3 inflammasome-mediated pyroptosis.ConclusionDeu@PEPS exerts prominent anti-inflammatory and anti-oxidative effects, which may offers a more patient-acceptable therapy with fewer adverse effects compared with oral deucravacitinib.

Intraspecific and interspecific variations in the synonymous codon usage in mitochondrial genomes of 8 pleurotus strains

In this study, we investigated the codon bias of twelve mitochondrial core protein coding genes (PCGs) in eight Pleurotus strains, two of which are from the same species. The results revealed that the codons of all Pleurotus strains had a preference for ending in A/T. Furthermore, the correlation between codon base compositions and codon adaptation index (CAI), codon bias index (CBI) and frequency of optimal codons (FOP) indices was also detected, implying the influence of base composition on codon bias. The two P. ostreatus species were found to have differences in various base bias indicators. The average effective number of codons (ENC) of mitochondrial core PCGs of Pleurotus was found to be less than 35, indicating strong codon preference of mitochondrial core PCGs of Pleurotus. The neutrality plot analysis and PR2-Bias plot analysis further suggested that natural selection plays an important role in Pleurotus codon bias. Additionally, six to ten optimal codons (ΔRSCU > 0.08 and RSCU > 1) were identified in eight Pleurotus strains, with UGU and ACU being the most widely used optimal codons in Pleurotus. Finally, based on the combined mitochondrial sequence and RSCU value, the genetic relationship between different Pleurotus strains was deduced, showing large variations between them. This research has improved our understanding of synonymous codon usage characteristics and evolution of this important fungal group.

Nuclear genomes of dinoflagellates reveal evolutionarily conserved pattern of RNA editing relative to stress response

Dinoflagellates are a group of diverse protists with complex genomes whose gene expression regulation mechanisms remain little known. RNA editing is a post-transcriptional regulatory mechanism of gene expression utilized by diverse species, and has been described primarily in the plastid and mitochondrial genomes of dinoflagellates. Its role in post-transcriptional regulation in the nuclear genomes of dinoflagellates remains largely unexplored. Here, integrating genome and transcriptome data from two dinoflagellate taxa in a comparative analysis, we identified 10,486 and 69,953 putative RNA editing sites in the nuclear genomes of the coral symbiont, Durusdinium trenchii CCMP2556 and the free-living bloom-forming taxon, Prorocentrum cordatum CCMP1329. We recovered all 12 possible types of RNA edits, with more edits representing transitions than transversions. In contrast to other eukaryotes, we found a dominance of A-to-T transversion in non-coding regions, many of which were condition-specific. Overall, the RNA editing sites implicate 7.5% of D. trenchii genes and 13.2% of P. cordatum genes. Some sites (1.5% in D. trenchii and more-substantially 62.3% in P. cordatum) were edited at significantly different frequencies in distinct growth conditions. The distribution of editing types and locations exhibited conserved patterns between the two phylogenetically distant species. Interestingly, A-to-T editing within the untranslated regions appear to be associated with upregulation of the edited genes in response to heat stress. These results lend support to the hypothesis that RNA editing is a key molecular mechanism that underpins regulation of gene expression in dinoflagellates.

Drug-Induced Fatty Liver Disease (DIFLD): A Comprehensive Analysis of Clinical, Biochemical, and Histopathological Data for Mechanisms Identification and Consistency with Current Adverse Outcome Pathways

Drug induced fatty liver disease (DIFLD) is a form of drug-induced liver injury (DILI), which can also be included in the more general metabolic dysfunction-associated steatotic liver disease (MASLD), which specifically refers to the accumulation of fat in the liver unrelated to alcohol intake. A bi-directional relationship between DILI and MASLD is likely to exist: while certain drugs can cause MASLD by acting as pro-steatogenic factors, MASLD may make hepatocytes more vulnerable to drugs. Having a pre-existing MASLD significantly heightens the likelihood of experiencing DILI from certain medications. Thus, the prevalence of steatosis within DILI may be biased by pre-existing MASLD, and it can be concluded that the genuine true incidence of DIFLD in the general population remains unknown. In certain individuals, drug-induced steatosis is often accompanied by concomitant injury mechanisms such as oxidative stress, cell death, and inflammation, which leads to the development of drug-induced steatohepatitis (DISH). DISH is much more severe from the clinical point of view, has worse prognosis and outcome, and resembles MASH (metabolic-associated steatohepatitis), as it is associated with inflammation and sometimes with fibrosis. A literature review of clinical case reports allowed us to examine and evaluate the clinical features of DIFLD and their association with specific drugs, enabling us to propose a classification of DIFLD drugs based on clinical outcomes and pathological severity: Group 1, drugs with low intrinsic toxicity (e.g., ibuprofen, naproxen, acetaminophen, irinotecan, methotrexate, and tamoxifen), but expected to promote/aggravate steatosis in patients with pre-existing MASLD; Group 2, drugs associated with steatosis and only occasionally with steatohepatitis (e.g., amiodarone, valproic acid, and tetracycline); and Group 3, drugs with a great tendency to transit to steatohepatitis and further to fibrosis. Different mechanisms may be in play when identifying drug mode of action: (1) inhibition of mitochondrial fatty acid β-oxidation; (2) inhibition of fatty acid transport across mitochondrial membranes; (3) increased de novo lipid synthesis; (4) reduction in lipid export by the inhibition of microsomal triglyceride transfer protein; (5) induction of mitochondrial permeability transition pore opening; (6) dissipation of the mitochondrial transmembrane potential; (7) impairment of the mitochondrial respiratory chain/oxidative phosphorylation; (8) mitochondrial DNA damage, degradation and depletion; and (9) nuclear receptors (NRs)/transcriptomic alterations. Currently, the majority of, if not all, adverse outcome pathways (AOPs) for steatosis in AOP-Wiki highlight the interaction with NRs or transcription factors as the key molecular initiating event (MIE). This perspective suggests that chemical-induced steatosis typically results from the interplay between a chemical and a NR or transcription factors, implying that this interaction represents the primary and pivotal MIE. However, upon conducting this exhaustive literature review, it became evident that the current AOPs tend to overly emphasize this interaction as the sole MIE. Some studies indeed support the involvement of NRs in steatosis, but others demonstrate that such NR interactions alone do not necessarily lead to steatosis. This view, ignoring other mitochondrial-related injury mechanisms, falls short in encapsulating the intricate biological mechanisms involved in chemically induced liver steatosis, necessitating their consideration as part of the AOP’s map road as well.

Review of archaic nymphomyiids (Diptera, Nymphomyiidae) of the Russian Far East and bordering territories, with describing of new taxa and DNA barcoding of known species

Nymphomyiidae from the Russian Far East and bordering territories are revised, including data on taxonomy, redescriptions, and results of DNA barcoding. Nymphomyia orientalis sp. nov. with two subspecies N orientalis orientalis subsp. nov. and N. orientalis makcha subsp. nov. are described and information on biology, ecology and distribution are presented. Key of Nymphomyia species for adult males and females of the world is provided. Three species delimitation approaches (ASAP, mPTP, GMYC) using the mitochondrial gene cytochrome c oxidase I (COI) confirm validity of described taxa as well as available nymphomyiids in GenBank. Morphologically indistinguishable specimens of N. orientalis sp. nov. from Makcha and Polovinka rivers belongs to separate mOTUs with the lowest distances in the genus 1.99% that is the lower interspecific threshold.

Distribution of mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes variants associated with hearing loss in Southwestern China

BackgroundMaternally inherited hearing loss has been associated with mitochondrial genes, including MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE. Among these genes, MT-RNR1 is known to be a hotspot for pathogenic variants related to aminoglycoside ototoxicity and nonsyndromic hearing loss. However, the frequency and spectrum of variants in these genes, particularly in multi-ethnic hearing loss patients from Southwestern China, are still not fully understood. MethodsIn this study, we enrolled 460 hearing loss patients from various ethnic backgrounds (Han, Yi, Dai, Hani, etc.) in Southwestern China. Next-generation sequencing was used to analyze the mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes. Subsequently, bioinformatical methods were employed to evaluate the identified variants. ResultsAmong the patients with hearing loss, we identified 70 variants in MT-RNR1 (78.6 %, 55/70), MT-TL1 (4.3 %, 3/70), MT-TS1 (4.3 %, 3/70), MT-TK (7.1 %, 5/70) and MT-TE (5.7 %, 4/70) genes. We found that 15 variants were associated with hearing loss, including m.1555 A > G and m.1095 T > C. Additionally, we discovered three reported mitochondrial variants (m.676 G > A, m.7465 insC, and m.7474 A > G) newly correlated with hearing loss. Notably, certain pathogenic variants, such as m.1555 A > G, displayed non-consistent distributions among the multi-ethnic patients with hearing loss. Furthermore, the number of variants associated with hearing loss was higher in the Sinitic group (n = 181) and Tibeto-Burman group (n = 215) compared to the Kra-Dai group (n = 38) and Hmong-Mien group (n = 26). ConclusionsThis present study revealed the distribution of mitochondrial variants linked to hearing loss across various ethnic groups in Southwestern China. These data suggest a potential correlation between the distribution of mitochondrial variants associated with hearing loss and ethnic genetic backgrounds.

Early life exposure to mercury and relationships with telomere length and mitochondrial DNA content in European children

BackgroundTelomere length (TL) and mitochondrial function expressed as mitochondrial DNA copy number (mtDNAcn) are biomarkers of aging and oxidative stress and inflammation, respectively. Methylmercury (MeHg), a common pollutant in fish, induces oxidative stress. We hypothesized that elevated oxidative stress from exposure to MeHg decreases mtDNAcn and shortens TL. MethodsStudy participants are 6–11-year-old children from the HELIX multi-center birth cohort study, comprising six European countries. Prenatal and postnatal total mercury (THg) concentrations were measured in blood samples, TL and mtDNAcn were determined in child DNA. Covariates and confounders were obtained by questionnaires. Robust regression models were run, considering sociodemographic and lifestyle covariates, as well as fish consumption. Sex, ethnicity, and fish consumption interaction models were also run. ResultsWe found longer TL with higher pre- and postnatal THg blood concentrations, even at low-level THg exposure according to the RfD proposed by the US EPA. The prenatal association showed a significant linear relationship with a 3.46 % increase in TL for each unit increased THg. The postnatal association followed an inverted U-shaped marginal non-linear relationship with 1.38 % an increase in TL for each unit increased THg until reaching a cut-point at 0.96 μg/L blood THg, from which TL attrition was observed. Higher pre- and postnatal blood THg concentrations were consistently related to longer TL among cohorts and no modification effect of fish consumption nor children's sex was observed. No association between THg exposure and mtDNAcn was found. DiscussionWe found evidence that THg is associated with TL but the associations seem to be time- and concentration-dependent. Further studies are needed to clarify the mechanism behind the telomere changes of THg and related health effects.

UV damage induces production of mitochondrial DNA fragments with specific length profiles.

UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). Photodamage and other bulky lesions occurring in nuclear genomes can be repaired through nucleotide excision repair (NER), where incisions on both sides of a damaged site precede the removal of a single-stranded oligonucleotide containing the damage. Mitochondrial genomes (mtDNAs) are also susceptible to damage from UV light, but current evidence suggests that the only way to eliminate bulky mtDNA damage is through mtDNA degradation. Damage-containing oligonucleotides excised during NER can be captured with anti-damage antibodies and sequenced (XR-seq) to produce high resolution maps of active repair locations following UV exposure. We analyzed previously published datasets from Arabidopsis thaliana, Saccharomyces cerevisiae, and Drosophila melanogaster to identify reads originating from the mtDNA (and plastid genome in A. thaliana). In A. thaliana and S. cerevisiae, the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt in S. cerevisiae and 28 nt in A. thaliana with distinct secondary peaks occurring in regular intervals. These reads also show a nonrandom distribution of di-pyrimidines (the substrate for CPD formation) with TT enrichment at positions 7-8 of the reads. Therefore, UV damage to mtDNA appears to result in production of DNA fragments of characteristic lengths and positions relative to the damaged location. The mechanisms producing these fragments are unclear, but we hypothesize that they result from a previously uncharacterized DNA degradation pathway or repair mechanism in mitochondria.

The genome sequence of a tachinid fly, Linnaemya tessellans (Robineau-Desvoidy, 1830)

We present a genome assembly from one male Linnaemya tessellans (tachinid fly; Arthropoda; Insecta; Diptera; Tachinidae). The genome sequence is 709.9 megabases in span. Most of the assembly is scaffolded into 7 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 17.24 kilobases in length.

The genome sequence of the Brown Ash Ermine moth, Zelleria hepariella Stainton, 1849

We present a genome assembly from a male Zelleria hepariella (the Brown Ash Ermine; Arthropoda; Insecta; Lepidoptera; Yponomeutidae). The genome sequence is 428.8 megabases in span. Most of the assembly is scaffolded into 19 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.31 kilobases in length. Gene annotation of this assembly on Ensembl identified 15,718 protein coding genes.

The genome sequence of the Brown Long-eared bat, Plecotus auritus (Linnaeus 1758)

We present a genome assembly from a female Plecotus auritus (Brown Long-eared bat; Chordata; Mammalia; Chiroptera; Vespertilionidae). The genome sequence is 2163.2 megabases in span. Most of the assembly is scaffolded into 16 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.91 kilobases in length.

Mitochondrial DNA Missense Mutations ChrMT: 8981A &gt; G and ChrMT: 6268C &gt; T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein–Barr Virus

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem disabling disease with unclear etiology and pathophysiology, whose typical symptoms include prolonged debilitating recovery from fatigue or postexertional malaise (PEM). Disrupted production of adenosine triphosphate (ATP), the intracellular energy that fuels cellular activity, is a cause for fatigue. Here, we present a long-term case of ME/CFS: a 75-year-old Caucasian female patient, whose symptoms of ME/CFS were clearly triggered by an acute infection of the Epstein–Barr virus 24 years ago (mononucleosis). Before then, the patient was a healthy professional woman. A recent DNA sequence analysis identified missense variants of mitochondrial respiratory chain enzymes, including ATP6 (ChrMT: 8981A &gt; G; Q152R) and Cox1 (ChrMT: 6268C &gt; T; A122V). Protein subunits ATP6 and Cox1 are encoded by mitochondrial DNA outside of the nucleus: the Cox1 gene encodes subunit 1 of complex IV (CIV: cytochrome c oxidase) and the ATP6 gene encodes subunit A of complex V (CV: ATP synthase). CIV and CV are the last two of five essential enzymes that perform the mitochondrial electron transport respiratory chain reaction to generate ATP. Further analysis of the blood sample using transmission electron microscopy demonstrated abnormal, circulating, extracellular mitochondria. These results indicate that the patient had dysfunctional mitochondria, which may contribute directly to her major symptoms, including PEM and neurological and cognitive changes. Furthermore, the identified variants of ATP6 (ChrMT: 8981A &gt; G; Q152R) and Cox1 (ChrMT: 6268C &gt; T; A122V), functioning at a later stage of mitochondrial ATP production, may play a role in the abnormality of the patient’s mitochondria and the development of her ME/CFS symptoms.