Mitochondrial DNA Research Articles

A consequential one-night stand: Episodic historical hybridization leads to mitochondrial takeover in sympatric desert ant-eating spiders

Disentangling the genomic intricacies underlying speciation and the causes of discordance between sources of evidence can offer remarkable insights into evolutionary dynamics. The ant-eating spider Zodarion nitidum, found across the Middle East and Egypt, displays yellowish and blackish morphs that co-occur sympatrically. These morphs additionally differ in behavioral and physiological features and show complete pre-mating reproductive isolation. In contrast, they possess similar sexual features and lack distinct differences in their mitochondrial DNA. We analyzed both Z. nitidum morphs and outgroups using genome-wide and additional mitochondrial DNA data. The genomic evidence indicated that Yellow and Black are reciprocally independent lineages without signs of recent admixture. Interestingly, the sister group of Yellow is not Black but Z. luctuosum, a morphologically distinct species. Genomic gene flow analyses pinpointed an asymmetric nuclear introgression event, with Yellow contributing nearly 5 % of its genome to Black roughly 320,000 years ago, intriguingly aligning with the independently estimated origin of the mitochondrial DNA of Black. We conclude that the blackish and yellowish morphs of Z. nitidum are long-diverged distinct species, and that the ancient and modest genomic introgression event registered resulted in a complete mitochondrial takeover of Black by Yellow. This investigation underscores the profound long-term effects that even modest hybridization events can have on the genome of organisms. It also exemplifies the utility of phylogenetic networks for estimating historical events and how integrating independent lines of evidence can increase the reliability of such estimations.

Human sperm mitochondrial DNA copy numbers and deletion rates: comparing persons living in two urban industrial agglomerations differing in sources of air pollution

Persons living in industrial environments are exposed to levels of air pollution that can affect their health and fertility. The Czech capital city, Prague, and the Ostrava industrial agglomeration differ in their major sources of air pollution. In Prague, heavy traffic produces high levels of nitrogen oxides throughout the year. In the Ostrava region, an iron industry and local heating are sources of particulate matter (PM) and benzo[a]pyrene (B[a]P), especially in the winter. We evaluated the effects of air pollution on human sperm mitochondrial DNA (mtDNA). Using real-time PCR, we analysed sperm mtDNA copy number and deletion rate in Prague city policemen in two seasons (spring and autumn) and compared the results with those from Ostrava. In Prague, the sperm mtDNA deletion rate was significantly higher in autumn than in spring, which is the opposite of the results from Ostrava. The sperm mtDNA copy number did not show any seasonal differences in either of the cities; it was correlated negatively with sperm concentration, motility, and viability, and with sperm chromatin integrity (assessed with the Sperm Chromatin Structure Assay). The comparison between the two cities showed that the sperm mtDNA deletion rate in spring and the sperm mtDNA copy number in autumn were significantly lower in Prague vs. Ostrava. Our study supports the hypothesis that sperm mtDNA deletion rate is affected by the composition of air pollution. Sperm mtDNA abundance is closely associated with chromatin damage and standard semen characteristics.

Mitochondrial genetic variations in leukemia: a comprehensive overview.

Leukemias are a group of heterogeneous hematological malignancies driven by diverse genetic variations, and the advent of genomic sequencing technologies facilitates the investigation of genetic abnormalities in leukemia. However, these sequencing-based studies mainly focus on nuclear DNAs. Increasing evidence indicates that mitochondrial dysfunction is an important mechanism of leukemia pathogenesis, which is closely related to the mitochondrial genome variations. Here, we provide an overview of current research progress concerning mitochondrial genetic variations in leukemia, encompassing gene mutations and copy number variations. We also summarize currently accessible mitochondrial DNA (mtDNA) sequencing methods. Notably, somatic mtDNA mutations may serve as natural genetic barcodes for lineage tracing and longitudinal assessment of clonal dynamics. Collectively, these findings enhance our understanding of leukemia pathogenesis and foster the identification of novel therapeutic targets and interventions.

Aldosterone, mitochondria and regulation of cardiovascular metabolic disease.

Aldosterone is a mineralocorticoid hormone involved in controlling electrolyte balance, blood pressure, and cellular signaling. It plays a pivotal role in cardiovascular and metabolic physiology. Excess aldosterone activates mineralocorticoid receptors, leading to subsequent inflammatory responses, increased oxidative stress, and tissue remodeling. Various mechanisms have been reported to link aldosterone with cardiovascular and metabolic diseases. However, mitochondria, responsible for energy generation through oxidative phosphorylation, have received less attention regarding their potential role in aldosterone-related pathogenesis. Excess aldosterone leads to mitochondrial dysfunction, and this may play a role in the development of cardiovascular and metabolic diseases. Aldosterone has the potential to affect mitochondrial structure, function, and dynamic processes, such as mitochondrial fusion and fission. In addition, aldosterone has been associated with the suppression of mitochondrial DNA, mitochondria-specific proteins, and ATP production in the myocardium through mineralocorticoid receptor, nicotinamide adenine dinucleotide phosphate oxidase, and reactive oxygen species pathways. In this review, we explore the mechanisms underlying aldosterone-induced cardiovascular and metabolic mitochondrial dysfunction, including mineralocorticoid receptor activation and subsequent inflammatory responses, as well as increased oxidative stress. Furthermore, we review potential therapeutic targets aimed at restoring mitochondrial function in the context of aldosterone-associated pathologies. Understanding these mechanisms is vital, as it offers insights into novel therapeutic strategies to mitigate the impact of aldosterone-induced mitochondrial dysfunction, thereby potentially improving the outcomes of individuals affected by cardiovascular and metabolic disorders.

Drug Target to Alleviate Mitochondrial Dysfunctions in Alzheimer's Disease: Recent Advances and Therapeutic Implications.

Alzheimer's disease (AD) is a severe progressive neurodegenerative condition associated with neuronal damage and reduced cognitive function that primarily affects the aged worldwide. While there is increasing evidence suggesting that mitochondrial dysfunction is one of the most significant factors contributing to AD, its accurate pathobiology remains unclear. Mitochondrial bioenergetics and homeostasis are impaired and defected during AD pathogenesis. However, the potential of mutations in nuclear or mitochondrial DNA encoding mitochondrial constituents to cause mitochondrial dysfunction has been considered since it is one of the intracellular processes commonly compromised in early AD stages. Additionally, electron transport chain dysfunction and mitochondrial pathological protein interactions are related to mitochondrial dysfunction in AD. Many mitochondrial parameters decline during aging, causing an imbalance in reactive oxygen species (ROS) production, leading to oxidative stress in age-related AD. Moreover, neuroinflammation is another potential causative factor in AD-associated mitochondrial dysfunction. While several treatments targeting mitochondrial dysfunction have undergone preclinical studies, few have been successful in clinical trials. Therefore, this review discusses the molecular mechanisms and different therapeutic approaches for correcting mitochondrial dysfunction in AD, which have the potential to advance the future development of novel drug-based AD interventions.

Melita panda, a new species of Melitidae (Crustacea, Amphipoda) from Japan

A new intertidal species of the melitid amphipod, Melita panda, from the Wakayama Prefecture, Japan, is identified and described. Melita pandasp. nov. differs from the similar M. koreana and M. nagatai by its black-and-white body color, well-developed anterodistal projection of the male gnathopod 1 propodus, and telson armature. Molecular phylogenetic analyses based on the nuclear 28S rRNA and mitochondrial COI genes support that M. pandasp. nov. is closely related to M. koreana and M. nagatai.

Characterization of the complete mitochondrial genome of Loxocephala sichuanensis (Hemiptera: Eurybrachidae) with the phylogenetic analyses of Fulgoromorpha

Little is known about the mitochondrial genome of the family Eurybrachidae, with only two species sequenced. This study added one more mitogenome of Loxocephala sichuanensis in this family. The mitochondrial genome length of this species was 15,605 bp, consisting of 37 genes: 13 PCGs, 2 rRNAs, 22 tRNAs, and a control region. An unusually high A + T content, reaching 94.3% at the third codon position of 13 PCGs in Loxocephala, was found in Eurybrachidae, which was the highest among all planthoppers, especially on N-strand. Three tandem repeat regions were detected in the control region. Phylogenetic analyses based on complete mitochondrial genome sequences from 145 species (encompassing 18 planthopper families and 135 species in Fulgoromorpha as ingroup, and 6 other non-planthopper families in Auchenorrhyncha as outgroup) were conducted. Six datasets (PCG123R24, PCG123R2, PCG123, PCG12R24, PCG12R2, PCG12) were established to investigate the influence of 22 tRNAs and the third codon of the 13 PCGs of mitogenome for phylogeny analyses. Both Maximum likelihood and Bayesian trees supported the monophyly of the superfamilies Delphacoidea and Fulgoroidea. Delphacoidea, consisting of Cixiidae and Delphacidae as sister group, was in the basal position of Fulgoromorpha. In Fulgoroidea, the families Meenoplidae and Kinnaridae, Dictyopharidae and Fulgoridae, Acanaloniidae and Tropiduchidae were sister groups which were strongly supported. Caliscelidae was close to the sister group Lophopidae with Eurybrachidae. The four families Flatidae, Nogodinidae, Ricaniidae and Issidae were closely related. The position of Tettigometridae was uncertain. Derbidae and Achilidae form a sister group when 22 tRNAs were included in the phylogeny. The joining of the tRNA sequences of mitochondrial genome enhanced the stability of family-level nodes and adjusted some phylogenetic positions, highlighting the significant role of joining tRNAs in phylogenetic analyses. Including or excluding the third codon position of 13 PCGs generally did not affect the overall phylogenetic structures of Fulgoromorpha.

Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation

Heat is a cardinal feature of inflammation, yet its impacts on immune cells remain uncertain. We show that moderate-grade fever temperatures (39°C) increased murine CD4 T cell metabolism, proliferation, and inflammatory effector activity while decreasing regulatory T cell suppressive capacity. However, heat-exposed T helper 1 (T H 1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways. Although many T H 1 cells subjected to such temperatures died, surviving T H 1 cells exhibited increased mitochondrial mass and enhanced activity. Electron transport chain complex 1 (ETC1) was rapidly impaired under fever-range temperatures, a phenomenon that was specifically detrimental to T H 1 cells. T H 1 cells with elevated DNA damage and ETC1 signatures were also detected in human chronic inflammation. Thus, fever-relevant temperatures disrupt ETC1 to selectively drive apoptosis or adaptation of T H 1 cells to maintain genomic integrity and enhance effector functions.

The complete mitochondrial genome of Uroobovella oviformis (Kontschan & Stary, 2011) (Acari, Urodinychidae) and its phylogenetic position within the order Mesostigmata

ABSTRACT Mitochondrial genomes are highly conserved in genetic processes and serve as a useful molecular marker for phylogenetic and evolutionary analysis. In this study, the complete mitochondrial genome of Uroobovella oviformis was sequenced and annotated. The mitochondrial genome is a closed, double-stranded circular molecule of 14,306 bp length and contains the typical 37 genes. All of the protein-coding genes started with ATN and terminated with TAA except COX2, COX3, and CYTB, which stopped with single T. The whole mitochondrial genome of U. oviformis showed a heavy AT nucleotide bias (77.69%), a positive AT-Skew (0.035), and a negative GC-Skew (−0.320), as well as translocation of seven genes including CYTB and ND6. The phylogenetic tree was constructed by Bayesian inference and maximum likelihood methods using three different datasets (PCG, PCG12, and AA), which were constructed to discuss the phylogenetic status of Mesostigmata. The analysis showed that the branching relationships among the six trees were consistent and all families except the Laelapidae were recovered as monophyletic. Furthermore, U. oviformis forms a separate clade and is located at the base of Mesostigmata and has a closer relationship with Antennophorina.

Oxazolidinone antibiotics impair ex vivo megakaryocyte differentiation from hematopoietic progenitor cells and their maturation into platelets

ABSTRACT Oxazolidinones (linezolid and tedizolid) adverse reactions include thrombocytopenia, the mechanism of which is still largely unknown. In cultured cells, oxazolidinones impair mitochondrial protein synthesis and oxidative metabolism. As mitochondrial activity is essential for megakaryocyte differentiation and maturation into platelets, we examined whether oxazolidinones impair these processes ex vivo and alter, in parallel, the activity of mitochondrial cytochrome c -oxidase (CYTOX; enzyme partly encoded by the mitochondrial genome) and cell morphology. Human CD34+ cells were isolated, incubated with cytokines (up to 14 days) and clinically relevant oxazolidinone concentrations or in control conditions, and used for (i) clonogenic assays [counting of megakaryocyte (CFU-Mk), granulocyte-monocyte (CFU-GM), burst-forming unit-erythroid (BFU-E) colonies]; (ii) the measure of the expression of megakaryocyte surface antigens (CD34 to CD41 and CD42); (iii) counting of proplatelets; (iv) the measurement of CYTOX activity; and (v) cell morphology (optic and electron microscopy). Oxazolidinones caused a significant decrease in BFU-E but not CFU-Mk or CFU-GM colonies. Yet, the megakaryocytic lineage was markedly affected, with a decreased differentiation of CD34+ into CD41+/CD42+ cells, an abolition of proplatelet formation and striking decrease in the numbers of large polylobulated nucleus megakaryocytes, with a complete loss of intracellular demarcation membrane system, disappearance of mitochondria, and suppression of CYTOX activity. These alterations were more marked in cells incubated with tedizolid than linezolid. These data suggest that oxazolidinones may induce thrombocytopenia by impairing megakaryocytic differentiation through mitochondrial dysfunction. Pharmacological interventions to prevent this toxicity might therefore be difficult as mitochondrial toxicity is most probably inherently linked to their antibacterial activity.

Recognizing Leber’s Hereditary Optic Neuropathy to avoid delayed diagnosis and misdiagnosis

Leber’s Hereditary Optic Neuropathy (LHON) is a maternally inherited optic nerve disease primarily caused by mutations in mitochondrial DNA (mtDNA). The peak of onset is typically between 15 and 30 years, but variability exists. Misdiagnosis, often as inflammatory optic neuritis, delays treatment, compounded by challenges in timely genetic diagnosis. Given the availability of a specific treatment for LHON, its early diagnosis is imperative to ensure therapeutic appropriateness. This work gives an updated guidance about LHON differential diagnosis to clinicians dealing also with multiple sclerosi and neuromyelitis optica spectrtum disorders-related optic neuritis. LHON diagnosis relies on clinical signs and paraclinical evaluations. Differential diagnosis in the acute phase primarily involves distinguishing inflammatory optic neuropathies, considering clinical clues such as ocular pain, fundus appearance and visual recovery. Imaging analysis obtained with Optical Coherence Tomography (OCT) assists clinicians in early recognition of LHON and help avoiding misdiagnosis. Genetic testing for the three most common LHON mutations is recommended initially, followed by comprehensive mtDNA sequencing if suspicion persists despite negative results. We present and discuss crucial strategies for accurate diagnosis and management of LHON cases.

Multiple distinct evolutionary mechanisms govern the dynamics of selfish mitochondrial genomes in Caenorhabditis elegans

Cells possess multiple mitochondrial DNA (mtDNA) copies, which undergo semi-autonomous replication and stochastic inheritance. This enables mutant mtDNA variants to arise and selfishly compete with cooperative (wildtype) mtDNA. Selfish mitochondrial genomes are subject to selection at different levels: they compete against wildtype mtDNA directly within hosts and indirectly through organism-level selection. However, determining the relative contributions of selection at different levels has proven challenging. We overcome this challenge by combining mathematical modeling with experiments designed to isolate the levels of selection. Applying this approach to many selfish mitochondrial genotypes in Caenorhabditis elegans reveals an unexpected diversity of evolutionary mechanisms. Some mutant genomes persist at high frequency for many generations, despite a host fitness cost, by aggressively outcompeting cooperative genomes within hosts. Conversely, some mutant genomes persist by evading inter-organismal selection. Strikingly, the mutant genomes vary dramatically in their susceptibility to genetic drift. Although different mechanisms can cause high frequency of selfish mtDNA, we show how they give rise to characteristically different distributions of mutant frequency among individuals. Given that heteroplasmic frequency represents a key determinant of phenotypic severity, this work outlines an evolutionary theoretic framework for predicting the distribution of phenotypic consequences among individuals carrying a selfish mitochondrial genome.

Licochalcone D from Glycyrrhiza uralensis Improves High-Glucose-Induced Insulin Resistance in Hepatocytes

This study investigated the therapeutic potential of licochalcone D (LicoD), which is derived from Glycyrrhiza uralensis, for improving glucose metabolism in AML12 hepatocytes with high-glucose-induced insulin resistance (IR). Ultra-high-performance liquid chromatography–mass spectrometry revealed that the LicoD content of G. uralensis was 8.61 µg/100 mg in the ethanol extract (GUE) and 0.85 µg/100 mg in the hot water extract. GUE and LicoD enhanced glucose consumption and uptake, as well as Glut2 mRNA expression, in high-glucose-induced IR AML12 cells. These effects were associated with the activation of the insulin receptor substrate/phosphatidylinositol-3 kinase signaling pathway, increased protein kinase B α phosphorylation, and suppression of gluconeogenesis-related genes, such as Pepck and G6pase. Furthermore, GUE and LicoD promoted glycogen synthesis by downregulating glycogen phosphorylase. Furthermore, LicoD and GUE mitigated the downregulated expression of mitochondrial oxidative phosphorylation proteins in IR hepatocytes by activating the PPARα/PGC1α pathway and increasing the mitochondrial DNA content. These findings demonstrate the potential of LicoD and GUE as therapeutic options for alleviating IR-induced metabolic disorders by improving glucose metabolism and mitochondrial function.

Cytoplasmic male sterility in plants with special emphasis on sugar beet

The phenomenon of cytoplasmic male sterility (CMS) in plants is characterized by a disturbance in the development of functional pollen. The cause of this disorder is the incompatibility of the mitochondrial and nuclear genome. Determinants of CMS are found in the mitochondrial genome and are inherited maternally. Nuclear Rf genes are responsible for restoring male fertility in CMS plants most often by posttranscriptional and/or posttranslational activity on mitochondrial gene expression. Two fertility restoring genes have been identified in sugar beet plants, of which Rf1 is the best characterized. It is concluded that the translation product of this gene acts as a molecular chaperone leading to inactivation of a specific mitochondrial protein that is a marker for the CMS trait in sugar beet. The CMS phenomenon is applied in the commercial breeding of hybrid varieties of many crop species. Exploiting heterosis is easier with the knowledge of cytoplasmic (mitochondrial) determinants of sterility and corresponding restorer genes.

The genome sequence of the ruby bryozoan, Bugula neritina (Linnaeus, 1758)

We present a genome assembly from a specimen of Bugula neritina (the ruby bryozoan; Bryozoa; Gymnolaemata; Cheilostomatida; Bugulidae). The genome sequence has total length of 216.00 megabases. Most of the assembly is scaffolded into 9 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 15.25 kilobases in length. Gene annotation of this assembly on Ensembl identified 20,264 protein-coding genes.

The genome sequence of the European conger eel, Conger conger (Linnaeus, 1758)

We present a genome assembly from an individual Conger conger (the European conger eel; Chordata; Actinopteri; Anguilliformes; Congridae). The genome sequence spans 1,136.40 megabases. Most of the assembly is scaffolded into 19 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 18.86 kilobases in length.

The genome sequence of the Pale Oak Beauty, Hypomecis punctinalis (Scopoli, 1763)

We present a genome assembly from an individual male Hypomecis punctinalis (the Pale Oak Beauty; Arthropoda; Insecta; Lepidoptera; Geometridae). The genome sequence has a total length of 741.20 megabases. Most of the assembly is scaffolded into 30 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.64 kilobases in length. Gene annotation of this assembly on Ensembl identified 13,897 protein-coding genes.

The genome sequence of an Entiminae weevil, Polydrusus pterygomalis Boheman, 1840

We present a genome assembly from an individual female Entiminae weevil, Polydrusus pterygomalis (Arthropoda; Insecta; Coleoptera; Curculionidae). The genome sequence has a total length of 1,051.50 megabases. Most of the assembly is scaffolded into 11 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 20.95 kilobases in length.

Whole genome sequence analysis of population structure and insecticide resistance markers in Anopheles melas from the Bijagós Archipelago, Guinea-Bissau

BackgroundAnopheles melas is an understudied malaria vector with a potential role in malaria transmission on the Bijagós Archipelago of Guinea-Bissau. This study presents the first whole-genome sequencing and population genetic analysis for this species from the Bijagós. To our knowledge, this also represents the largest population genetic analysis using WGS data from non-pooled An. melas mosquitoes.MethodsWGS was conducted for 30 individual An. melas collected during the peak malaria transmission season in 2019 from six different islands on the Bijagós Archipelago. Bioinformatics tools were used to investigate the population structure and prevalence of insecticide resistance markers in this mosquito population.ResultsInsecticide resistance mutations associated with pyrethroid resistance in Anopheles gambiae s.s. from the Bijagós were absent in the An. melas population, and no signatures of selective sweeps were identified in insecticide resistance-associated genes. Analysis of structural variants identified a large duplication encompassing the cytochrome-P450 gene cyp9k1. Phylogenetic analysis using publicly available mitochondrial genomes indicated that An. melas from the Bijagós split into two phylogenetic groups because of differentiation on the mitochondrial genome attributed to the cytochrome C oxidase subunits COX I and COX II and the NADH dehydrogenase subunits 1, 4, 4L and 5.ConclusionsThis study identified an absence of insecticide-resistant SNPs common to An. gambiae in the An. melas population, but did identify structural variation over insecticide resistance-associated genes. Furthermore, this study presents novel insights into the population structure of this malaria vector using WGS analysis. Additional studies are required to further understand the role of this vector in malaria transmission.Graphical abstract

The genome sequence of the Bindweed Bent-wing moth, Bedellia somnulentella (Zeller, 1847)

We present a genome assembly from an individual female Bindweed Bent-wing moth, Bedellia somnulentella (Arthropoda; Insecta; Lepidoptera; Bedelliidae). The genome sequence has a length of 549.00 megabases. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the W and Z sex chromosomes. The mitochondrial genome has also been assembled and is 16.62 kilobases in length. Gene annotation of this assembly on Ensembl identified 11,959 protein-coding genes.