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The jaguar (Panthera onca) is the largest living cat species native to the Americas and one of few large American carnivorans to have survived into the Holocene. However, the extent to which jaguar diversity declined during the end-Pleistocene extinction event remains unclear. For example, Pleistocene jaguar fossils from North America are notably larger than the average extant jaguar, leading to hypotheses that jaguars from this continent represent a now-extinct subspecies (Panthera onca augusta) or species (Panthera augusta). Here, we used a hybridization capture approach to recover an ancient mitochondrial genome from a large, late Pleistocene jaguar from Kingston Saltpeter Cave, Georgia, United States, which we sequenced to 26-fold coverage. We then estimated the evolutionary relationship between the ancient jaguar mitogenome and those from other extinct and living large felids, including multiple jaguars sampled across the species' current range. The ancient mitogenome falls within the diversity of living jaguars. All sampled jaguar mitogenomes share a common mitochondrial ancestor ~400 thousand years ago, indicating that the lineage represented by the ancient specimen dispersed into North America from the south at least once during the late Pleistocene. While genomic data from additional and older specimens will continue to improve understanding of Pleistocene jaguar diversity in the Americas, our results suggest that this specimen falls within the variation of extant jaguars despite the relatively larger size and geographic location and does not represent a distinct taxon.

The Black-throated Gray Warbler (Setophaga nigrescens) is a migratory songbird with a widespread and continuous distribution in the North American West. Previously published morphological data support the designation of 2 putative subspecies based on subtle differences in plumage and song; however, whether these patterns are clinal or discrete has yet to be determined. Furthermore, given that patterns of morphological variation occur across multiple distinct habitats and geographical boundaries, underlying population genetic structure may be present. To investigate this question and explore the evolutionary history of S. nigrescens, we conducted the first range-wide phylogeographic analysis of this species using genetic (mitochondrial DNA [mtDNA], ND2 gene sequences), morphological (body measurements), and environmental (niche modeling) data. Overall, our results identified 2 major mtDNA clades. One clade occurs east of the Cascade-Sierra ranges throughout the southwestern, Great Basin, and Rocky Mountain regions in North America (Interior clade), while a second widespread clade is comprised of birds that span the Pacific Northwest, and also across the Great Basin and southwest into the Rocky Mountains (Coastal clade). Divergence time estimates suggest a Pleistocene epoch vicariance event. Environmental niche models predict habitat modification and fragmentation from glacial-interglacial cycles, which were frequent over the Pleistocene. Range expansion northwards following the Last Glacial Maximum was identified from neutrality tests and shifts in suitable habitat from the Mid-Holocene to present-day conditions, where both clades arc likely experiencing secondary contact. We found support for nonequivalent environmental niches among both clades based on a spatial analysis of environmental variables, with the Coastal clade showing greater tolerance to both temperate and xeric climatic conditions across the North American West; however, the environmental space occupied by both clades was more similar to each other than expected by chance. High levels of geographic overlap and a lack of discrete patterns in morphology suggest few contemporary reproductive barriers to gene flow. Received 12 July 2023. Accepted 27 February 2024. Key words: gene tree, mitochondrial DNA, morphology, niche divergence, niche modeling, Pleistocene vicariance, subspecies delimitation. La reinita Setophaga nigrescens es un ave canora migratoria con una distribucion amplia y continua en el Oeste Norteamericano. Datos morfologicos previamente publicados apoyan la denominacion de 2 subespecies putativas basadas en diferencias sutiles en plumaje y canto; sin embargo, aun no se determina si esos patrones son cunales o discretos. Ademas, dado que los patrones de variacion morfologica ocurren en multiples habitats separados con limites geograficos definidos, podria estar presente una estructura poblacional genetica subyacente. Para estudiar esta pregunta y explorar la historia evolutiva de 5. nigrescens, condujimos el primer analisis filogenetico de todo el rango de distribucion de esta especie usando datos geneticos (ADN mitocondrial [mtDNA], secuencias geneticas ND2), morfologicos (medidas corporales) y ambientales (modelamiento de nicho). En general, nuestros resultados identificaron 2 ciados mayores de mtDNA. Un ciado se encuentra en las cordilleras Cascade-Sierra hacia el sudoeste y las regiones de Great Bassin y Rocky Mountain en Norte America (ciado Interior), mientras que un segundo ciado se compone de aves que se enceuntran en el Pacifico noroeste, ademas de a traves del Great Bassin y el sudoeste de las Rocky Mountains (ciado Costero). Los tiempos de divergencias estimados sugieren un evento de vicarianza en la epoca del Pleistoceno. Modelos de nicho ambiental predicen una modificacion y fragmentacion del habitat durante ciclos interglaciales, que eran frecuentes en el Pleistoceno. Una expansion de rango hacia el norte a partir del Ultimo Maximo Glacial frie identificada de pruebas de neutralidad y cambios de habitat favorables de condiciones del Holoceno medio a las actuales, donde ambos ciados posiblemente experimentaron contacto secundario. Encontramos apoyo para nichos ambientales no equivalentes entre ambos ciados basados en el analisis especial de variables ambientales, donde el ciado Costero mostro mayor tolerancia tanto a temperatura como a condiciones climaticas xericas a traves del Oeste Norteamericano; sin embargo, el espacio ambiental ocupado por ambos ciados era mas similar entre ellos que lo esperado por el azar. Altos niveles de sobrelapamiento geografico y una falta de patrones discretos morfologicos sugieren pocas barreras reproductivas contemporaneas al flujo genico. Palabras clave: ADN mitocondrial, arbol genetico, delimitacion de subespecies, divergencia de nicho, modelamiento de nicho, morfologia, vicarianza en el Pleistoceno., Evolutionary biologists have long been interested in investigating how historical and contemporary processes have influenced patterns of biodiversity across the globe. In particular, the historical events associated with Pleistocene glaciations [...]

The northern quahog, Mercenaria mercenaria (= hard clam) is an important aquaculture species on the U.S. east coast and shares a partially sympatric distribution with a sister species Mercenaria campechiensis which is endemic to the mid-Atlantic coast from the Chesapeake Bay to Florida and the Gulf of Mexico. These two species are morphologically similar, and their identification is laborious and challenging. To support aquaculture breeding and restoration activities, it is essential to develop an accurate and easy method to identify the two Mercenaria species. In the present study, high-melting resolution analysis was applied to identify these two Mercenaria species and their hybrids using three genes of cytochrome oxidase subunit 1 (COJ), mitochondrial large ribosomal subunit (I6S r RNA), and internal transcribed spacer 1 (ITSI). The temperature melting points (TJ of COl, 16S rRNA, and ITSI were significantly different between the two Mercenaria species and could be used to distinguish M. mercenaria and M. campechiensis. By use of the melting T of COl, 16S r RNA, and ITSI, a discriminant function equation was established to effectively eliminate the impacts of intraspecific sequence variations on species identification. Compared with their true species classification, the accuracy of the predicted classification of each sample was 100% based on the discriminant function equation. Furthermore, a linear discriminant analysis model was used for cross-validation and the mean classification success was 100% with no observed erroneous classification. Moreover, the interspecific hybrids of M. mercenaria and M. campechiensis were verified by the melting curve of nuclear DNA marker ITSI, and their maternity was further clarified by mitochondrial DNA markers COl and 16S rRNA. The methodology developed in this study would be useful as a rapid and accurate tool to support Mercenaria aquaculture, breeding, and restoration. KEY WORDS: high-resolution melt analysis, Mercenaria mercenaria, Mercenaria campechiensis, species identification, hybrid, discriminant analysis, INTRODUCTION The northern quahog, Mercenaria mercenaria (also named hard clam) is an intertidal benthic infaunal species along the western Atlantic coast from the Gulf of St. Lawrence to Florida (Harte [...]

A new mitochondrial genome is the most gene-rich one found in a major division of eukaryotes — and it shares remarkable features with that of one of its most distant relatives. [ABSTRACT FROM AUTHOR]

Leber’s hereditary optic neuropathy (LHON) causes subacute visual loss, and, in the acute phase, the optic disc shows hyperemia, peripapillary telangiectasia, and swelling of the retinal nerve fiber layer (RNFL). Rarely, retinal hemorrhage may be present. In this study, we investigated LHON cases with retinal hemorrhage in the acute phase. Among 82 cases (164 eyes) of LHON who visited the Inoue Eye Hospital, retinal hemorrhage was observed in 5 cases (5 eyes). The age at onset was 36 (27–46) years, with 4 male cases. Mitochondrial DNA analysis revealed the presence of the m.11778G > A variant in four patients and the m.14484T > C variant in one patient. There was no medical history and no excessive smoking or alcohol consumption in any of the cases. In all cases, retinal hemorrhages were observed in the RNFL, accompanying the characteristic optic disc findings of LHON. Fluorescein angiography performed in three cases showed no leakage from the optic disc or blood vessels. While rare, the presence of retinal hemorrhage along the RNFL during the acute phase of LHON should be recognized, as it may warrant consideration of alternative diagnoses. [ABSTRACT FROM AUTHOR]

Historical periods of rapid climate change and associated direct and indirect impacts such as glaciation and restructuring of drainage systems are important in shaping biodiversity, lineage divergence, and contemporary genetic variation amongst many aquatic taxa. Through an understanding of the impacts of these ancient changes in land‐ and waterscapes on current diversity, practitioners can account for a species' unique evolutionary history when developing conservation strategies. We investigated intraspecific genetic diversity of the critically endangered freshwater mussel, Lampsilis rafinesqueana, endemic to the interior region of the U.S.A. Our study (1) characterises genetic variation within and amongst populations to infer biogeographic history and (2) applies genetic information to potential conservation strategies. We applied restriction‐site associated DNA sequencing and mitochondrial DNA sequencing to investigate genetic diversity within and amongst populations of L. rafinesqueana from across the species' distribution. We then considered this information in the context of historical riverscape processes and applicability to conservation. Variation within rivers was similar, but we found different genetic populations associated with two major ecoregions, the Central Interior Highlands and Osage Plains. The plains population displayed an Ne value approximately 10‐fold lower than the highlands population. Historical demographic modelling suggests the two populations diverged approximately 1.2 million years ago and then both populations underwent a substantial decrease in population size around 19,700 years ago. These two major events are each correlated with known periods of historic rapid climate change. We identified two distinct populations of a federally endangered mussel, L. rafinesqueana. Contemporary genetic diversity of this species was strongly influenced by direct and indirect impacts of rapid historic shifts in climate. The highlands population has undergone a recent expansion, typical of post‐Pleistocene climate change, while also having a much larger Ne value than the plains population. Our results suggest low levels of gene flow amongst the two distinct populations across generations. We recommend that conservation managers for this species take into account relative difference in diversity between populations when developing management strategies. In many species, assisted gene flow amongst genetically unique populations should only be considered in extreme circumstances; however, in L. rafinesqueana, low levels of assisted migration amongst populations may be a valuable tactic to maintain natural levels of genetic variation. Our study shows that biogeographical frameworks can be useful for developing conservation strategies that serve to retain important genomic variation that represents the evolutionary potential of target freshwater species. [ABSTRACT FROM AUTHOR]

Invasive species are one of the leading causes of biodiversity loss. During demographic monitoring of native turtle species in northeast Spain, we captured several alien species of semi-aquatic turtles, including Mauremys mutica. Among them, four individuals of this latter species showed external characteristics that were not fully consistent with the diagnosis of this species. These individuals showed a smaller postocular stripe and 2-3 lateral cervical lines and the typical plastral pattern observed in Mauremys leprosa. The analysis of mitochondrial DNA indicated that the maternal lineage was unequivocally M. mutica (pure or hybrid), but nuclear DNA revealed a heterozygote position at the C-mos gene, matching sequences for this gene in GenBank from both M. leprosa and M. mutica. These results highlight the negative impact of alien turtles, which can genetically contaminate vulnerable native turtle populations. [ABSTRACT FROM AUTHOR]

The European endemic barbels represent important bioindicators of river quality and are nowadays threatened by changing environmental conditions and hybridization with the invasive alien Barbus barbus. It is therefore fundamental to investigate interactions among species and adaptability to climate changes in protected areas of Northern Apennines. An investigation was carried out considering 248 barbel samples that were analysed for Cytb mitochondrial DNA and 192 at 10 microsatellite loci, to delineate the distribution and population structure of the two native species as well as the impact of invasive B. barbus inside 15 sites of the Natura 2000 network. The complex distribution of the native barbel species was highlighted, together with a significant genetic structure emerging in different populations. Only one site revealed a “pure” population of B. caninus while the other ones showed a high level of hybridization between the different barbel species. For the B. plebejus two “genetically pure” populations were found in the hill‐mountain sector, while the hybridization level resulted in increasing in the lowest altitudinal stretch of watercourses with a consistent contribution driven by B. barbus. We herein present the first evidence of B. barbus introgression along an altitudinal gradient, carried from the lowland water course to mountain stretches driven by B. plebejus migration. B. plebejus is the species that can act as vicariant organism able to transfer the B. barbus genome from the plain habitats into B. caninus genome of the higher altitude waterstreams, as a consequence of habitat shifts due to climate changes and anthropogenic acitivities. [ABSTRACT FROM AUTHOR]

An editorial is presented on mitochondrial plasticity and quality control in health and disease. Topics include the investigation of mitochondrial dysfunction in various pathological conditions, the exploration of therapeutic interventions targeting mitochondria, and the role of mitochondria in development and differentiation.

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage. [ABSTRACT FROM AUTHOR]

Protein import and genome replication are essential processes for mitochondrial biogenesis and propagation. The J-domain proteins Pam16 and Pam18 regulate the presequence translocase of the mitochondrial inner membrane. In the protozoan Trypanosoma brucei, their counterparts are TbPam16 and TbPam18, which are essential for the procyclic form (PCF) of the parasite, though not involved in mitochondrial protein import. Here, we show that during evolution, the 2 proteins have been repurposed to regulate the replication of maxicircles within the intricate kDNA network, the most complex mitochondrial genome known. TbPam18 and TbPam16 have inactive J-domains suggesting a function independent of heat shock proteins. However, their single transmembrane domain is essential for function. Pulldown of TbPam16 identifies a putative client protein, termed MaRF11, the depletion of which causes the selective loss of maxicircles, akin to the effects observed for TbPam18 and TbPam16. Moreover, depletion of the mitochondrial proteasome results in increased levels of MaRF11. Thus, we have discovered a protein complex comprising TbPam18, TbPam16, and MaRF11, that controls maxicircle replication. We propose a working model in which the matrix protein MaRF11 functions downstream of the 2 integral inner membrane proteins TbPam18 and TbPam16. Moreover, we suggest that the levels of MaRF11 are controlled by the mitochondrial proteasome. Pam16 and Pam18 are conserved co-chaperones essential for mitochondrial protein import in eukaryotes, but not in the parasite Trypanosoma brucei. This study shows that the function of TbPam16/18 has been repurposed during evolution to regulate the replication of maxicircles within the T. brucei mitochondrial genome. [ABSTRACT FROM AUTHOR]

We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1019 treatment-naive persons with HIV (PWH) who initiated first-line antiretroviral therapy (ART) since 2014. The mean increase in weight and BMI over the study period was 2.90 kg and 0.98 kg/m2, respectively. We found a significant adjusted association between the major UK mtDNA haplogroup and lower weight and BMI increase at 96 weeks after ART initiation. Our findings reveal a potential role for mitochondrial genetics in the complex phenomenon of weight gain after initial ART in PWH. [ABSTRACT FROM AUTHOR]

The diverse climatic and geological history of Southeast Asia has been a driving force behind significant Pleistocene and Holocene range dynamics and the consequent biological diversification in the region. Among the species exhibiting wide distributions, extending across several well-known zoogeographic barriers, the Elongated Tortoise (Indotestudo elongata) is noted for its extensive variability in size, shape, and colouration. To examine phylogeographic differentiation within I. elongata, we analysed three mitochondrial gene fragments (ND4, cyt b, and COI) for 52 individuals including fourteen historic specimens and 25 sequences obtained from Gen- Bank. Phylogenetic analyses of the concatenated alignment revealed genetic homogeneity across the range, supported by a shallow mean uncorrected p distance of 1.2% in cyt b. This corresponds to a surprising lack of biogeographic structuring. Concordantly, multivariate statistical analyses of morphometric and colouration-related characters of 166 adult tortoises (79 males and 87 females) from Myanmar, Thailand, Cambodia, and Vietnam showed no statistically significant differences between biogeographic units. The lack of any phylogeographic signal and morphological differentiation despite the presence of significant biogeographic barriers is unusual for a terrestrial vertebrate from this region. Archaeological evidence suggests that Elongated Tortoises have been used as a food item for millennia. It could be that their current wide distribution and the absence of genetic differentiation are the result of a significant range expansion caused by extensive human-mediated dispersal over the prehistoric and historic tortoise trade. The observed lack of phylogeographic structure considerably simplifies conservation measures such as conservation breeding, reintroduction, and population reinforcement. [ABSTRACT FROM AUTHOR]

Interbreeding and introgression between recently diverged species is common. However, the processes that prevent these species from merging where they co‐occur are not well understood. We studied the mechanisms that allowed an isolated group of populations of the snail Helix thessalica to persist within the range of the related Helix pomatia despite high gene flow. Using genomic cline analysis, we found that the nuclear gene flow between the two taxa across the mosaic hybrid zone was not different from that expected under neutral admixture, but that the exchange of mtDNA was asymmetric. Tests showed that there is relaxed selection in the mitochondrial genome of H. thessalica and that the substitution rate is elevated compared to that of H. pomatia. A lack of hybrids that combine the mtDNA of H. thessalica with a mainly (>46%) H. pomatia genomic background indicates that the nuclear‐encoded mitochondrial proteins of H. pomatia are not well adapted to the more rapidly evolving proteins and RNAs encoded by the mitochondrion of H. thessalica. The presumed reduction of fitness of hybrids with the fast‐evolving mtDNA of H. thessalica and a high H. pomatia ancestry, similar to 'Darwin's Corollary to Haldane's rule', resulted in a relative loss of H. pomatia nuclear ancestry compared to H. thessalica ancestry in the hybrid zone. This probably prevents the H. thessalica populations from merging quickly with the surrounding H. pomatia populations and supports the hypothesis that incompatibilities between rapidly evolving mitochondrial genes and nuclear genes contribute to speciation. [ABSTRACT FROM AUTHOR]

Mitochondria are essential organelles because they generate the energy required for cellular functions. Kidney stones, as one of the most common urological diseases, have garnered significant attention. In this study, we first collected peripheral venous blood from patients with kidney stones and used qRT-PCR to detect mitochondrial DNA (mtDNA) copy number as a means of assessing mitochondrial function in these patients. Subsequently, through Western blotting, qPCR, immunofluorescence, immunohistochemistry, and transmission electron microscopy, we examined whether calcium oxalate crystals could cause mitochondrial dysfunction in the kidney in both in vitro and in vivo. We then examined the intersection of the DEGs obtained by transcriptome sequencing of the mouse kidney stone model with mitochondria-related genes, and performed KEGG and GO analyses on the intersecting genes. Finally, we administered the mitochondrial ROS scavenger Mito-Tempo in vivo and observed its effects. Our findings revealed that patients with kidney stones had a reduced mtDNA copy number in their peripheral venous blood compared to the control group, suggesting mitochondrial dysfunction in this population. This conclusion was further validated through in vitro and in vivo experiments. Enrichment analyses revealed that the intersecting genes were closely related to metabolism. We observed that after mitochondrial function was preserved, the deposition of calcium oxalate crystals decreased, and the kidney damage and inflammation caused by them were also alleviated. Our research indicates that kidney stones can cause mitochondrial dysfunction. After clearing mtROS, the damage and inflammation caused by kidney stones are reversed, providing new insights into the prevention and treatment of kidney stones. [ABSTRACT FROM AUTHOR]

The genus Dendrobium, part of the Orchidaceae family, encompasses species of significant medicinal, nutritional, and economic value. However, many Dendrobium species are threatened by environmental stresses, low seed germination rates, and overharvesting. Mitochondria generate the energy necessary for various plant life activities. Despite their importance, research on the mitochondrial genomes of Dendrobium species is currently limited. To address this gap, we performed a comprehensive genetic analysis of four Dendrobium species--D. flexicaule, D. nobile, D. officinale, and D. huoshanense--focusing on their mitochondrial and chloroplast genomes to elucidate their genetic architecture and support conservation efforts. We utilized advanced sequencing technologies, including Illumina for highthroughput sequencing and Nanopore for long-read sequencing capabilities. Our findings revealed the multichromosomal mitochondrial genome structures, with total lengths ranging from 596,506 bp to 772,523 bp. The mitochondrial genomes contained 265 functional genes, including 64-69 protein-coding genes, 23-28 tRNA genes, and 3 rRNA genes. We identified 647 simple sequence repeats (SSRs) and 352 tandem repeats, along with 440 instances of plastid-to-mitochondrial gene transfer. Additionally, we predicted 2,023 RNA editing sites within the mitochondrial protein-coding genes, predominantly characterized by cytosine-to-thymine transitions. Comparative analysis of mitochondrial DNA across the species highlighted 25 conserved genes, with evidence of positive selection in five genes: ccmFC, matR, mttB, rps2, and rps10. Phylogenetic assessments suggested a close sister relationship between D. nobile and D. huoshanense, and a similar proximity between D. officinale and D. flexicaule. This comprehensive genomic study provides a critical foundation for further exploration into the genetic mechanisms and biodiversity of Dendrobium species, contributing valuable insights for their conservation and sustainable utilization. [ABSTRACT FROM AUTHOR]

The Mediterrane an Sea is a biodiversity hotspot, being home to a vast array of marine species. Furthermore, seawater warming is facilitating the arrival and spread of new thermophilic species, posing a severe threat to biodiversity. Among the species currently extending their range and increasing in abundance in Mediterranean waters, sea chubs (genus Kyphosus) are one of the most enigmatic. One challenge arises from the high phenotypic similarity between the two congeneric species documented in the basin: Kyphosus vaigiensis and Kyphosus sectatrix. Their resemblance has often led to identification challenges, resulting in incorrect or omitted species-level classifications. Therefore, despite the growing presence of these fish in the Mediterranean, it remains unclear whether only one or both species are experiencing a demographic increase and range extension. To date, there have been 26 reports of Kyphosus individuals in the Mediterranean Sea, documented in 24 separate papers. Here, we reviewed the history of the genus in the basin and provided 13 new records of these fish from multiple localities along Mediterranean coasts. In addition, we sequenced the entire mitogenomes of two specimens, assessed their phylogenetic relationships with published Kyphosus mitochondrial DNAs from around the world, and conducted detailed morphological and meristic analyses on one of them, allowing us to provide accurate species-level identifications. Our results indicate that K. vaigiensis is the species currently expanding its range in the Mediterranean Sea, while K. sectatrix is still very rare and only sporadically reported. Notably, our mitogenome data indicate that Mediterranean K. vaigiensis individuals most likely came from Atlantic waters, while there is no evidence to support an entrance through the Red Sea or any other anthropogenic vector. Finally, the potential ecological and fishing impacts associated with the proliferation of these fish in the region are discussed. [ABSTRACT FROM AUTHOR]

We characterized the complete mitogenome of Nemipterus randalli and performed comparative mitogenomic analysis with previously determined mitochondrial genomes belonging to the family Nemipteridae. Using Sanger sequencing, we identified a 16,642 bp mitogenome containing 37 genes (13 protein-coding, 2 rRNA, 22 tRNA) and a non-coding region. Its gene organization, nucleotide composition, tRNA secondary structure and codon usage are similar to other Nemipteridae mitogenomes. The phylogenetic analysis indicated that Nemipteridae is a monophyletic group. The present study forms the basis for further studies on the population genetics, evolution and phylogeny of N. randalli and its family. [ABSTRACT FROM AUTHOR]

Background: Although rheumatoid arthritis (RA) is a chronic systemic tissue disease often accompanied by osteoporosis (OP), the molecular mechanisms underlying this association remain unclear. This study aimed to elucidate the pathogenesis of RA and OP by identifying differentially expressed mRNAs (DEmRNAs) and long non-coding RNAs (lncRNAs) using a bioinformatics approach. Methods: Expression profiles of individuals diagnosed with OP and RA were retrieved from the Gene Expression Omnibus database. Differential expression analysis was conducted. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway enrichment analyses were performed to gain insights into the functional categories and molecular/biochemical pathways associated with DEmRNAs. We identified the intersection of common DEmRNAs and lncRNAs and constructed a protein-protein interaction (PPI) network. Correlation analysis between the common DEmRNAs and lncRNAs facilitated the construction of a coding-non-coding network. Lastly, serum peripheral blood mononuclear cells (PBMCs) from patients with RA and OP, as well as healthy controls, were obtained for TRAP staining and qRT-PCR to validate the findings obtained from the online dataset assessments. Results: A total of 28 DEmRNAs and 2 DElncRNAs were identified in individuals with both RA and OP. Chromosomal distribution analysis of the consensus DEmRNAs revealed that chromosome 1 had the highest number of differential expression genes. GO and KEGG analyses indicated that these DEmRNAs were primarily associated with " platelets (PLTs) degranulation", "platelet alpha granules", "platelet activation", "tight junctions" and "leukocyte transendothelial migration", with many genes functionally related to PLTs. In the PPI network, MT-ATP6 and PTGS1 emerged as potential hub genes, with MT-ATP6 originating from mitochondrial DNA. Co-expression analysis identified two key lncRNA-mRNA pairs: RP11 − 815J21.2 with MT − ATP6 and RP11 − 815J21.2 with PTGS1. Experimental validation confirmed significant differential expression of RP11-815J21.2, MT-ATP6 and PTGS1 between the healthy controls and the RA + OP groups. Notably, knockdown of RP11-815J21.2 attenuated TNF + IL-6-induced osteoclastogenesis. Conclusions: This study successfully identified shared dysregulated genes and potential therapeutic targets in individuals with RA and OP, highlighting their molecular similarities. These findings provide new insights into the pathogenesis of RA and OP and suggest potential avenues for further research and targeted therapies. [ABSTRACT FROM AUTHOR]

Background: Fritillaria ussuriensis is an endangered medicinal plant known for its notable therapeutic properties. Unfortunately, its population has drastically declined due to the destruction of forest habitats. Thus, effectively protecting F. ussuriensis from extinction poses a significant challenge. A profound understanding of its genetic foundation is crucial. To date, research on the complete mitochondrial genome of F. ussuriensis has not yet been reported. Results: The complete mitochondrial genome of F. ussuriensis was sequenced and assembled by integrating PacBio and Illumina sequencing technologies, revealing 13 circular chromosomes totaling 737,569 bp with an average GC content of 45.41%. A total of 55 genes were annotated in this mitogenome, including 2 rRNA genes, 12 tRNA genes, and 41 PCGs. The mitochondrial genome of F. ussuriensis contained 192 SSRs and 4,027 dispersed repeats. In the PCGs of F. ussuriensis mitogenome, 90.00% of the RSCU values exceeding 1 exhibited a preference for A-ended or U-ended codons. In addition, 505 RNA editing sites were predicted across these PCGs. Selective pressure analysis suggested negative selection on most PCGs to preserve mitochondrial functionality, as the notable exception of the gene nad3 showed positive selection. Comparison between the mitochondrial and chloroplast genomes of F. ussuriensis revealed 20 homologous fragments totaling 8,954 bp. Nucleotide diversity analysis revealed the variation among genes, and gene atp9 was the most notable. Despite the conservation of GC content, mitogenome sizes varied significantly among six closely related species, and colinear analysis confirmed the lack of conservation in their genomic structures. Phylogenetic analysis indicated a close relationship between F. ussuriensis and Lilium tsingtauense. Conclusions: In this study, we sequenced and annotated the mitogenome of F. ussuriensis and compared it with the mitogenomes of other closely related species. In addition to genomic features and evolutionary position, this study also provides valuable genomic resources to further understand and utilize this medicinal plant. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Amyotrophic lateral sclerosis (ALS) may be familial or sporadic, and twin studies have revealed that even sporadic forms have a significant genetic component. Variants in 55 nuclear genes have been associated with ALS and although mitochondrial dysfunction is observed in ALS, variants in mitochondrial genomes (mitogenomes) have not yet been tested for association with ALS. The aim of this study was to determine whether mitogenome variants are associated with ALS.We conducted a genome‐wide association study (GWAS) in mitogenomes of 1965 ALS patients and 2547 controls.We identified 51 mitogenome variants with p values <10−7, of which 13 had odds ratios (ORs) >1, in genes RNR1, ND1, CO1, CO3, ND5, ND6, and CYB, while 38 variants had OR <1 in genes RNR1, RNA2, ND1, ND2, CO2, ATP8, ATP6, CO3, ND3, ND4, ND5, ND6, and CYB. The frequencies of haplogroups H, U, and L, the most frequent in our ALS data set, were the same in different onset sites (bulbar, limb, spinal, and axial). Also, intra‐haplogroup GWAS revealed unique ALS‐associated variants in haplogroups L and U.Our study shows that mitogenome single nucleotide variants (SNVs) are associated with ALS and suggests that these SNVs could be included in routine genetic testing for ALS and that mitochondrial replacement therapy has the potential to serve as a basis for ALS treatment. [ABSTRACT FROM AUTHOR]

Mitochondrial diseases (MtDs) present diverse clinical phenotypes, yet large‐scale studies are hindered by their rarity. This retrospective, multicenter study, conducted across five Chinese hospitals' neurology departments from 2009 to 2019, aimed to address this gap. Nationwide, 1351 patients were enrolled, with a median onset age of 14.0 (18.5) years. The predominant phenotype was mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS) (45.0%). Mitochondrial DNA (mtDNA) mutations were prevalent (87.4%), with m.3243A>G being the most common locus (48.7%). Meanwhile, POLG mutations in nuclear DNA (nDNA) accounted for 16.5%. Comparative analysis based on age groups (with a cut‐off at 14 years) revealed the highest prevalence of MELAS, with Leigh syndrome (LS) and chronic progressive external ophthalmoplegia (CPEO) being the second most common phenotypes in junior and senior groups, respectively. Notably, the most commonly mutated nuclear genes varied across age groups. In conclusion, MELAS predominated in this Chinese MtD cohort, underscored by m.3243A>G and POLG as principal mtDNA mutations and pathogenic nuclear genes. The phenotypic and genotypic disparities observed among different age cohorts highlight the complex nature of MtDs. [ABSTRACT FROM AUTHOR]

Cardiotoxicity is the leading side effect of anthracycline‐based chemotherapy. Therefore, it has gained importance to reveal chemotherapy‐supporting strategies and reliable agents with their mechanisms of action. Tannic acid (TA), a naturally occurring plant polyphenol, has diverse physiological effects, including anti‐inflammatory, anticarcinogenic, antioxidant, and radical scavenging properties. Therefore, this study was designed to investigate whether TA exerts a protective effect on mechanisms contributing to anthracycline‐induced cardiotoxicity in rat heart tissues exposed to doxorubicin (DOX). Rats were randomly divided into control and experimental groups and treated with (18 mg/kg) DOX, TA (50 mg/kg), and DOX + TA during the 2 weeks. Cardiac gene markers and mitochondrial DNA (mtDNA) content were evaluated in the heart tissues of all animals. In addition to major metabolites, mRNA expression changes and biological activity responses of components of antioxidant metabolism were examined in the heart tissues of all animals. The expression of cardiac gene markers increased by DOX exposure was significantly reduced by TA treatment, whereas mtDNA content, which was decreased by DOX exposure, was significantly increased. TA also improved antioxidant metabolism members' gene expression and enzymatic activity, including glutathione peroxidase, glutathione s‐transferase, superoxide dismutase, catalase, and thioredoxin reductase. This study provides a detailed overview of the current understanding of DOX‐induced cardiotoxicity and preventive or curative measures involving TA. [ABSTRACT FROM AUTHOR]

Background: Sepsis represents a severe manifestation of infection often accompanied by metabolic disorders and mitochondrial dysfunction. Notably, mitochondrial DNA copy number (mtDNA-CN) and the expression of specific mitochondrial genes have emerged as sensitive indicators of mitochondrial function. To investigate the utility of mitochondrial gene expression in peripheral blood cells for distinguishing severe infections and predicting associated outcomes, we conducted a prospective cohort study. Methods: We established a prospective cohort comprising 74 patients with non-sepsis pneumonia and 67 cases of sepsis induced by respiratory infections, aging from 2 to 6 years old. We documented corresponding clinical data and laboratory information and collected blood samples upon initial hospital admission. Peripheral blood cells were promptly isolated, and both total DNA and RNA were extracted. We utilized absolute quantification PCR to assess mtDNA-CN, as well as the expression levels of mt-CO1, mt-ND1, and mt-ATP6. Subsequently, we extended these comparisons to include survivors and non-survivors among patients with sepsis using univariate and multivariate analyses. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic potential. Results: The mtDNA-CN in peripheral blood cells was significantly lower in the sepsis group. Univariate analysis revealed a significant reduction in the expression of mt-CO1, mt-ND1, and mt-ATP6 in patients with sepsis. However, multivariate analysis did not support the use of mitochondrial function in peripheral blood cells for sepsis diagnosis. In the comparison between pediatric sepsis survivors and non-survivors, univariate analysis indicated a substantial reduction in the expression of mt-CO1, mt-ND1, and mt-ATP6 among non-survivors. Notably, total bilirubin (TB), mt-CO1, mt-ND1, and mt-ATP6 levels were identified as independent risk factors for sepsis-induced mortality. ROC curves were then established for these independent risk factors, revealing areas under the curve (AUCs) of 0.753 for TB (95% CI 0.596-0.910), 0.870 for mt-CO1 (95% CI 0.775-0.965), 0.987 for mt-ND1 (95% CI 0.964-1.000), and 0.877 for mt-ATP6 (95% CI 0.793-0.962). Conclusion: MtDNA-CN and mitochondrial gene expression are closely linked to the severity and clinical outcomes of infectious diseases. Severe infections lead to impaired mitochondrial function in peripheral blood cells. Notably, when compared to other laboratory parameters, the expression levels of mt-CO1, mt-ND1, and mt-ATP6 demonstrate promising potential for assessing the prognosis of pediatric sepsis. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis. One-sentence summary: GSDME inflames ICI-associated myocarditis. ICI-induced myocarditis is fatal, but its mechanism is unclear. Here, the authors identify GSDME as a key driver by promoting cGAS-STING signaling, enhancing our understanding of its pathogenesis. [ABSTRACT FROM AUTHOR]

Episyrphus balteatus can provide dual ecosystem services including pest control and pollination, which the larvae are excellent predators of aphid pest whereas adults are efficient pollinator. In this study, we assembled a high-quality genome of E. balteatus from northern China geographical population at the chromosome level by using Illumina, PacBio long reads, and Hi-C technologies. The 467.42 Mb genome was obtained from 723 contigs, with a contig N50 of 9.16 Mb and Scaffold N50 of 118.85 Mb, and 90.25% (431.75 Mb) of the assembly was anchored to 4 pseudo-autosomes and one pseudo-heterosome. In total, 14,848 protein-coding genes were annotated, and 95.14% of genes were fully represented in NR, GO, KEGG databases. Besides, we also obtained the mitochondrial genome of E. balteatus of 16, 837 bp in length with 37 typical mitochondrial genes. Overall, this high-quality genome is valuable for evolutionary and genetic studies of E. balteatus and other Syrphidae hoverfly species. [ABSTRACT FROM AUTHOR]

Enhanced survival and reproduction are associated with an individual's direct and indirect social connections with members of a group. Yet, the role of these connections is little known in a vast range of primate species. We studied female Central Himalayan Langur (CHL) to investigate the link between four specific attributes (dominance rank, age, genetic relatedness, and the presence of females carrying infants) and a female's direct and indirect social relationships. By analyzing grooming networks, we revealed different behavioral strategies: high‐ranking females form relationships with many females (high degree), whereas females with dependent infants have strong relationships (high strength and eigenvector). Subadult females are important individuals that hold the social network together (high betweenness), while an immigrant female strategy is to integrate herself into the group by forming strong bonds with females who themselves have strong bonds (high eigenvector). Our study sheds light on how behavioral strategies shape female CHL grooming networks, which may help them to secure fitness and survival advantages. Research Highlights: The female social network in Central Himalayan Langurs was revealed by investigating the grooming interactions and attributes (dominance rank, age, genetic relatedness, and presence of female‐carrying infants).Results showed that high‐ranking females form relationships with many females and that females with dependent infants formed stronger bonds with each other.Also, subadult age group was considered important to intermediate connections in the social network, while the immigrant female had a tendency to make strong bonds with females who have strong bonds with others to integrate into the group. [ABSTRACT FROM AUTHOR]

Background: Primary mitochondrial diseases (PMDs) are the most common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. They can result from mutations in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). These disorders are multisystemic and mainly affect high energy‐demanding tissues, such as muscle and the central nervous system (CNS). Among many clinical features of CNS involvement, parkinsonism is one of the most common movement disorders in PMDs. Methods: This review provides a pragmatic educational overview of the most recent advances in the field of mitochondrial parkinsonism, from pathophysiology and genetic etiologies to phenotype and diagnosis. Results: mtDNA maintenance and mitochondrial dynamics alterations represent the principal mechanisms underlying mitochondrial parkinsonism. It can be present in isolation, alongside other movement disorders or, more commonly, as part of a multisystemic phenotype. Mutations in several nuclear‐encoded genes (ie, POLG, TWNK, SPG7, and OPA1) and, more rarely, mtDNA mutations, are responsible for mitochondrial parkinsonism. Progressive external opthalmoplegia and optic atrophy may guide genetic etiology identification. Conclusion: A comprehensive deep‐phenotyping approach is needed to reach a diagnosis of mitochondrial parkinsonism, which lacks distinctive clinical features and exemplifies the intricate genotype‐phenotype interplay of PMDs. [ABSTRACT FROM AUTHOR]

Mitochondrial missense mutations and pathogenic variants have been implicated in the pathogenesis of COVID-19. This study evaluated the role of mitochondrial DNA (mtDNA) mutations and changes in gene expression in the progression of COVID-19 and their correlation with clinical characteristics. Next-generation sequencing with high throughput was used to identify mtDNA mutations in 30 COVID-19 patients compared to 20 healthy controls. The potential impact of identified mutations on protein structure and stability was predicted using bioinformatic tools. Quantitative real-time polymerase chain reaction was employed to assess the expression levels of mtDNAencoded genes involved in oxidative phosphorylation in COVID-19 patients and healthy controls. Correlations between gene expression levels, clinical parameters, including leukocyte, lymphocyte, neutrophil, and platelet count, as well as creatinine, alanine transaminase (ALT), aspartate transaminase (AST), and blood urea nitrogen (BUN) levels, and disease severity were analyzed. We found 8 different mtDNA mutations in ND1, ND5, CO3, ATP6, and CYB genes, which were predicted to alter amino acids and decrease protein stability. Two missense unique mutations, C9555T in CO3 and A12418T in ND5 were identified and correlated with Complexes I and IV, respectively. This downregulation was correlated with age, elevated levels of leukocytes, lymphocytes, neutrophils, platelets, creatinine, ALT, AST, and BUN, as well as disease severity. These findings suggest that mtDNA mutations and altered expression of oxidative phosphorylation genes contribute to mitochondrial dysfunction in COVID-19. Targeting mitochondrial dysfunction may represent a promising therapeutic strategy for COVID-19 treatment. [ABSTRACT FROM AUTHOR]

Summary: Erythroid cells undergo a highly complex maturation process, resulting in dynamic changes that generate red blood cells (RBCs) highly rich in haemoglobin. The end stages of the erythroid cell maturation process primarily include chromatin condensation and nuclear polarization, followed by nuclear expulsion called enucleation and clearance of mitochondria and other organelles to finally generate mature RBCs. While healthy RBCs are devoid of mitochondria, recent evidence suggests that mitochondria are actively implicated in the processes of erythroid cell maturation, erythroblast enucleation and RBC production. However, the extent of mitochondrial participation that occurs during these ultimate steps is not completely understood. This is specifically important since abnormal RBC retention of mitochondria or mitochondrial DNA contributes to the pathophysiology of sickle cell and other disorders. Here we review some of the key findings so far that elucidate the importance of this process in various aspects of erythroid maturation and RBC production under homeostasis and disease conditions. [ABSTRACT FROM AUTHOR]

This study aimed to comprehensively assess the metabolic, mitochondrial, and inflammatory effects of first-line efavirenz, emtricitabine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) single-tablet regimen (STR) relative to untreated asymptomatic HIV infection. To this end, we analyzed 29 people with HIV (PWH) treated for at least one year with this regimen vs. 33 antiretroviral-naïve PWH. Excellent therapeutic activity was accompanied by significant alterations in metabolic parameters. The treatment group showed increased plasmatic levels of glucose, total cholesterol and its fractions (LDL and HDL), triglycerides, and hepatic enzymes (GGT, ALP); conversely, bilirubin levels (total and indirect fraction) decreased in the treated cohort. Mitochondrial performance was preserved overall and treatment administration even promoted the recovery of mitochondrial DNA (mtDNA) content depleted by the virus, although this was not accompanied by the recovery in some of their encoded proteins (since cytochrome c oxidase II was significantly decreased). Inflammatory profile (TNFα, IL-6), ameliorated after treatment in accordance with viral reduction and the recovery of TNFα levels correlated to mtDNA cell restoration. Thus, although this regimen causes subclinical metabolic alterations, its antiviral and anti-inflammatory properties may be associated with partial improvement in mitochondrial function. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a neurodegenerative disorder primarily known for typical motor features that arise due to the loss of dopaminergic neurons in the substantia nigra. However, the precise molecular aetiology of the disease is still unclear. Several cellular pathways have been linked to Parkinson's disease, including the autophagy-lysosome pathway, α-synuclein aggregation and mitochondrial function. Interestingly, the mechanistic link between GBA1 , the gene that encodes for lysosomal β-glucocerebrosidase (GCase), and Parkinson's disease lies in the interplay between GCase functions in the lysosome and mitochondria. GCase mutations alter mitochondria-lysosome contact sites. In the lysosome, reduced GCase activity leads to glycosphingolipid build-up, disrupting lysosomal function and autophagy, thereby triggering α-synuclein accumulation. Additionally, α-synuclein aggregates reduce GCase activity, creating a self-perpetuating cycle of lysosomal dysfunction and α-synuclein accumulation. GCase can also be imported into the mitochondria, where it promotes the integrity and function of mitochondrial complex I. Thus, GCase mutations that impair its normal function increase oxidative stress in mitochondria, the compartment where dopamine is oxidized. In turn, the accumulation of oxidized dopamine adducts further impairs GCase activity, creating a second cycle of GCase dysfunction. The oxidative state triggered by GCase dysfunction can also induce mitochondrial DNA damage which, in turn, can cause dopaminergic cell death. In this review, we highlight the pivotal role of GCase in Parkinson's disease pathogenesis and discuss promising examples of GCase-based therapeutics, such as gene and enzyme replacement therapies, small molecule chaperones and substrate reduction therapies, among others, as potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Across eukaryotes, most genes required for mitochondrial function have been transferred to, or otherwise acquired by, the nucleus. Encoding genes in the nucleus has many advantages. So why do mitochondria retain any genes at all? Why does the set of mtDNA genes vary so much across different species? And how do species maintain functionality in the mtDNA genes they do retain? In this review, we will discuss some possible answers to these questions, attempting a broad perspective across eukaryotes. We hope to cover some interesting features which may be less familiar from the perspective of particular species, including the ubiquity of recombination outside bilaterian animals, encrypted chainmail-like mtDNA, single genes split over multiple mtDNA chromosomes, triparental inheritance, gene transfer by grafting, gain of mtDNA recombination factors, social networks of mitochondria, and the role of mtDNA dysfunction in feeding the world. We will discuss a unifying picture where organismal ecology and gene-specific features together influence whether organism X retains mtDNA gene Y, and where ecology and development together determine which strategies, importantly including recombination, are used to maintain the mtDNA genes that are retained. [ABSTRACT FROM AUTHOR]

Neuromuscular features are common in mitochondrial DNA (mtDNA) disorders. The genetic architecture of mtDNA disorders in diverse populations is poorly understood. We analysed mtDNA variants from whole‐exome sequencing data in neuromuscular patients from South Africa, Brazil, India, Turkey and Zambia. In 998 individuals, there were two definite diagnoses, two possible diagnoses and eight secondary findings. Surprisingly, common pathogenic mtDNA variants found in people of European ancestry were very rare. Whole‐exome or ‐genome sequencing from undiagnosed patients with neuromuscular symptoms should be re‐analysed for mtDNA variants, but the landscape of pathogenic mtDNA variants differs around the world. [ABSTRACT FROM AUTHOR]

Collecting and preserving biological samples in the field, particularly in remote areas in tropical forests, prior to laboratory analysis is challenging. Blood samples in many cases are used for nucleic acid‐based species determination, genomics or pathogen research. In most cases, maintaining a cold chain is impossible and samples remain at ambient temperature for extended periods of time before controlled storage conditions become available. Dried blood spot (DBS) storage, blood stored on cellulose‐based paper, has been widely applied to facilitate sample collection and preservation in the field for decades. However, it is unclear how long‐term storage on this substrate affects nucleic acid concentration and integrity. We analysed nucleic acid quality from DBS stored on Whatman filter paper no. 3 and FTA cards for up to 15 years in comparison to cold‐chain stored samples using four nucleic acid extraction methods. We examined the ability to identify viral sequences from samples of 12 free‐ranging primates in the Amazon forest, using targeted hybridization capture, and determined if mitochondrial genomes could be retrieved. The results suggest that even after extended periods of storage, DBS will be suitable for some genomic applications but may be of limited use for viral pathogen research, particularly RNA viruses. [ABSTRACT FROM AUTHOR]

The capybara, Hydrochoerus hydrochaeris, is a rodent that inhabits the wetlands of South America. Despite being widely distributed and having the nuclear genomes available, there has been a lack of information regarding the mitochondrial genome. To address this, we conducted the assembly and annotation of the capybara's mitochondrial genome and reconstructed the phylogeny of Parvorder Caviomorpha. The assembly was conducted under the de novo method with GetOrganelle, while the annotation was performed with MitoZ. Analysis of relative codon synonymous usage was conducted in the mitochondrial genomes of the capybara and two other Caviidae species: Cavia porcellus and Cavia aperea. The phylogenetic inference was conducted under the Maximum Likelihood method, using the 13 protein-coding genes, including the capybara as well as other 42 Caviomorpha mitochondrial genomes. The resulting capybara mitochondrial genome consisted of 16,681 bp, 37 genes (22 tRNAs, 2 rRNAs, and 13 protein-coding genes) and a control region. The number of genes and their arrangement corresponds to the pattern observed in most mammalian species. The capybara was recovered as a sister group of Cavia. Caviidae was reconstructed as a monophyletic group that is closely related to Cuniculidae. Overall, this study provides valuable insights into the mitochondrial evolution and evolutionary relationships of the capybara. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Massive genotyping in cattle has uncovered several deleterious haplotypes that cause preterm mortality. Holstein haplotype 5 (HH5) is a deleterious haplotype present in the Holstein Friesian population that involves the ablation of the transcription factor B1 mitochondrial (TFB1M) gene. The developmental stage at which HH5 double-carrier (DC, homozygous) embryos or fetuses die remains unknown and this is a relevant information to estimate the economic losses associated with the inadvertent cross between carriers. To determine whether HH5 DC survive to maternal recognition of pregnancy, embryonic day (E) 14 embryos were flushed from superovulated carrier cows inseminated with a carrier bull. Double-carrier E14 conceptuses were recovered at Mendelian rates but they failed to achieve early elongation, as evidenced by a drastic reduction of their extra-embryonic membranes, which were >26-fold shorter than those of carrier or noncarrier embryos. To assess development at earlier stages, TFB1M knockout (KO) embryos—functionally equivalent to DC embryos—were generated by clustered regularly interspaced short palindromic repeats (CRISPR) technology and cultured to the blastocyst stage, in vitro culture day (D) 8, and to the early embryonic disc stage, D12. No significant effect of TFB1M ablation was observed on the differentiation and proliferation of embryonic lineages and relative mitochondrial DNA (mtDNA) content up to D12. In conclusion, HH5 DC embryos are able to develop to early embryonic disc stage but fail to undergo early conceptus elongation, which is required for pregnancy recognition. [ABSTRACT FROM AUTHOR]

Aim: The distribution of within‐species lineages has been affected by Quaternary climate changes, and population differentiation has been influenced by species life history traits. We investigated whether the distribution of individual mitochondrial genetic lineages reflects the constituent species' traits. Using the functionally diverse group of butterflies, we examined which lineages are present in Central Europe, an important suture zone. Location: Czech Republic and Western Palearctic. Taxon: A total of 140 butterfly species. Methods: We sequenced DNA barcodes (cytochrome c oxidase 1) (959 sequences) of the entire Czech Republic butterfly fauna and used Barcoding of Life Data System to visualise the species' biogeographic patterns across Europe. We categorised the distribution patterns of lineages inhabiting the Czech Republic, and used multivariate statistics to interpret these categories by the butterflies' habitats, life history traits and threat levels. Results: Open habitat dwellers with specialist traits belonged to Eastern, Southern and temperate lineages. Habitat generalists and woodland dwellers belonged to the Western lineage, formed several lineages or displayed low genetic diversity; they often developed on woody plants, were large‐winged and had long flight periods. The most threatened species were the specialists of Southern, Eastern and temperate lineages. Main Conclusions: The distribution of lineages in Central Europe reflects the history of Quaternary ecosystems: during cold periods of the Pleistocene, the diverse open habitats prevailed and species could expand westwards. Such species also suffer the most under the current anthropogenic habitat alteration. On the other hand, the mobile generalists and woodland dwellers expanded to Central Europe during the Holocene. Our approach of linking the distribution of lineages with species traits can be transferred to other study systems, and we show that DNA barcoding of under‐sampled areas represents a powerful tool for discovering the driving forces of biogeography. [ABSTRACT FROM AUTHOR]

Aim: Knowledge of taxonomy and species distributions in highly diverse lineages of invertebrates remains too incomplete for the study of biogeographical patterns at the global scale. This limits the understanding of processes leading to the formation and maintenance of boundaries between major biogeographical realms. Site‐based metagenomic approaches may provide an alternative source of data for inference of historical processes of in situ speciation and interchange among biogeographical regions. We applied the methodology to explore the historical biogeography of the Qinling Mountains at the boundary of the Oriental and Palaearctic regions. Location: The focal area in the Qinling Mountains; sites in Borneo, Panama, and Spain, representing the Oriental, Neotropical and Palaearctic faunas. Time Period: Contemporary. Major Taxa Studied: Chrysomelidae, a group of ~40,000 species with worldwide distribution. Methods: Mass‐trapped insects were subjected to deep Illumina DNA sequencing and mitochondrial genome assembly, followed by phylogenetic analysis and historical biogeographical inference on a dated tree. The methodology produced 622 mitogenomes (304 newly sequenced) each representing a morphologically distinct species. Results: Ancestral area reconstruction revealed that the Qinling fauna is a composite of distinct clades that, respectively, have Oriental or Palaearctic ancient origins, while in situ speciation and local clade formation were limited. The global diversity of Chrysomelidae consists of regionalised deep clades at the level of the major zoogeographic realms, which remain recognisable where these realms abut in the Qinling mountains. Yet, the Qinling fauna is clearly distinct from the source areas although local lineage ages are generally <20 Ma. Main Conclusions: The Qinling fauna is a composite of clades that have either Oriental or Palaearctic origin, indicating the important role of immigration at the realm boundary. Global site‐based phylogenetic analyses based on metagenomic sequencing can address previously intractable questions about the historical biogeography of poorly studied groups even without a fully developed taxonomy. [ABSTRACT FROM AUTHOR]

The population of the Northwest Pre-Caspian saiga (Saiga tatarica tatarica) numbered about 800 000 individuals in the middle of the last century. There was a dramatic decline at the end of the 20th century, and by 2015 the numbers of this saiga population reached about five thousand animals. The results of microsatellite loci and of mtDNA control region analysis obtained for museum saiga samples from the Northwest Pre-Caspian population, collected at the peak of their numbers in the 1950s, are presented. We compared these data with our previous results for the samples collected during the population depression in the years 1999–2016. There were no noticeable differences in the mtDNA control region diversity between the museum and modern saiga samples. The most vivid genetic consequence of the severe decline in population numbers was a significant increase of the inbreeding coefficient (Fis) calculated from the microsatellite loci. [ABSTRACT FROM AUTHOR]

Intermittent hypoxia (IH) is the predominant pathophysiological disturbance in obstructive sleep apnea (OSA), characterized by neuronal cell death and neurocognitive impairment. We focus on the accumulated mitochondrial DNA (mtDNA) in the cytosol, which acts as a damage-associated molecular pattern (DAMP) and activates the cyclic GMP-AMP synthase (cGAS)—stimulator of interferon genes (STING) pathway, a known trigger for immune responses and neuronal death in degenerative diseases. However, the specific role and mechanism of the mtDNA-cGAS-STING axis in IH-induced neural damage remain largely unexplored. Here, we investigated the involvement of PANoptosis, a novel type of programmed cell death linked to cytosolic mtDNA accumulation and the cGAS-STING pathway activation, in neuronal cell death induced by IH. Our study found that PANoptosis occurred in primary cultures of hippocampal neurons and HT22 cell lines exposed to IH. In addition, we discovered that during IH, mtDNA released into the cytoplasm via the mitochondrial permeability transition pore (mPTP) activates the cGAS-STING pathway, exacerbating PANoptosis-associated neuronal death. Pharmacologically inhibiting mPTP opening or depleting mtDNA significantly reduced cGAS-STING pathway activation and PANoptosis in HT22 cells under IH. Moreover, our findings indicated that the cGAS-STING pathway primarily promotes PANoptosis by modulating endoplasmic reticulum (ER) stress. Inhibiting or silencing the cGAS-STING pathway substantially reduced ER stress-mediated neuronal death and PANoptosis, while lentivirus-mediated STING overexpression exacerbated these effects. In summary, our study elucidates that cytosolic escape of mtDNA triggers cGAS-STING pathway-dependent neuronal PANoptosis in response to IH, mainly through regulating ER stress. The discovery of the novel mechanism provides theoretical support for the prevention and treatment of neuronal damage and cognitive impairment in patients with OSA. [ABSTRACT FROM AUTHOR]

Background: Autosomal dominant tubulointerstitial kidney disease (ADTKD) results from mutations in various genes, including REN, UMOD, MUC1, and HNF1B. ADTKD due to REN mutations (ADTKD-REN) is often characterized as a proteinopathy that triggers the endoplasmic reticulum stress (ERS) cascade, potentially sharing similarities with ADTKD-UMOD and ADTKD-MUC1 at the cellular level. This study, inspired by a patient harboring a W17R mutation, investigates ERS activation by this mutation alongside two other renin variants, W10R and L381P. Methods: We established stable cell lines expressing both wild-type and mutated renin forms (W17R, W10R, and L381P). Using luciferase reporter assays, RT-qPCR, and confocal microscopy, we evaluated ERS activation, determined the cellular localization of the renin variants, and characterized the mitochondrial network in the W17R line. Results: The L381P line exhibited ERS activation, including transcriptional upregulation of MANF and CRELD2. No ERS activation was observed in the W17R line, while the W10R line exhibited intermediate characteristics. Notably, the W17R variant was misrouted to the mitochondria resulting in changes of the mitochondrial network organisation. Conclusions: ERS activation is not a universal response to different renin mutations in ADTKD-REN. The pathogenesis of the W17R mutation may involve mitochondrial dysfunction rather than the ER pathway, albeit further research is needed to substantiate this hypothesis fully. Testing CRELD2 and MANF as targeted therapy markers for a specific subgroup of ADTKD-REN patients is recommended. Additionally, fludrocortisone treatment has shown efficacy in stabilizing the renal function of our patient over a four-year period without significant side effects. [ABSTRACT FROM AUTHOR]

Accumulative evidence indicates a critical role of mitochondrial function in autism spectrum disorders (ASD), implying that ASD risk may be linked to mitochondrial dysfunction due to DNA (mtDNA) variations. Although a few studies have explored the association between mtDNA variations and ASD, the role of mtDNA in ASD is still unclear. Here, we aimed to investigate whether mitochondrial DNA haplogroups are associated with the risk of ASD. Two European cohorts and an Ashkenazi Jewish (AJ) cohort were analyzed, including 2,062 ASD patients in comparison with 4,632 healthy controls. DNA samples were genotyped using Illumina HumanHap550/610 and Illumina 1M arrays, inclusive of mitochondrial markers. Mitochondrial DNA (mtDNA) haplogroups were identified from genotyping data using HaploGrep2. A mitochondrial genome imputation pipeline was established to detect mtDNA variants. We conducted a case-control study to investigate potential associations of mtDNA haplogroups and variants with the susceptibility to ASD. We observed that the ancient adaptive mtDNA haplogroup K was significantly associated with decreased risk of ASD by the investigation of 2 European cohorts including a total of 2,006 cases and 4,435 controls (odds ratio = 0.64, P= 1.79 × 10–5), and we replicated this association in an Ashkenazi Jewish (AJ) cohort including 56 cases and 197 controls (odds ratio = 0.35, P = 9.46 × 10–3). Moreover, we demonstrate that the mtDNA variants rs28358571, rs28358584, and rs28358280 are significantly associated with ASD risk. Further expression quantitative trait loci (eQTLs) analysis indicated that the rs28358584 and rs28358280 genotypes are associated with expression levels of nearby genes in brain tissues, suggesting those mtDNA variants may confer risk for ASD via regulation of expression levels of genes encoded by the mitochondrial genome. This study helps to shed light on the contribution of mitochondria in ASD and provides new insights into the genetic mechanism underlying ASD, suggesting the potential involvement of mtDNA-encoded proteins in the development of ASD. Increasing evidence indicates that mitochondrial dysfunction may be linked to autism spectrum disorder (ASD). This study investigated potential associations of mitochondrial DNA (mtDNA) variants in 2 European and Ashkenazi Jewish cohorts including 2,062 individuals with ASD and 4,632 healthy controls. Researchers found that the ancient mtDNA haplogroup K was linked to a reduced risk of ASD in both European and Ashkenazi Jewish populations. Additionally, specific mtDNA variants were associated with ASD risk and were shown to influence the expression of nearby genes in the brain. These findings highlight the potential involvement of mtDNA in ASD development, offering new insights into the genetic mechanisms underlying the disorder. [ABSTRACT FROM AUTHOR]

Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS–STING pathway, which is crucial for innate immunity. This pathway responds to mitochondrial DNA and is associated with cellular stress response. Our review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS–STING pathway. We critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions, primarily through the accumulation of damaged mitochondria, which activates the cGAS–STING pathway. This activation prompts the production of pro-inflammatory cytokines, exacerbating neuroinflammation. This review emphasizes the interaction between mitophagy and the cGAS–STING pathways. Effective mitophagy may suppress the cGAS–STING pathway, offering protection against neuroinflammation. Conversely, impaired mitophagy may activate the cGAS–STING pathway, leading to chronic neuroinflammation. Additionally, we explored how this interaction influences neurodegenerative disorders, suggesting a common mechanism underlying these diseases. In conclusion, there is a need for additional targeted research to unravel the complexities of mitophagy–cGAS–STING interactions and their role in neurodegeneration. This review highlights potential therapies targeting these pathways, potentially leading to new treatments for neuroinflammatory and neurodegenerative conditions. This synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research. Crosstalk between autophagy and cGAS–STING in microglia activation is vital for neurodegeneration, orchestrating shifts from M0 to M1/M2 phenotypes, crucial for maintaining neuronal survival and blood–brain barrier integrity. [Display omitted] [ABSTRACT FROM AUTHOR]

The present study evaluated the cardioprotective effect of astaxanthin (ASX) against isoproterenol (ISO) induced myocardial infarction in rats via the pathway of mitochondrial biogenesis as the possible molecular target of astaxanthin. The control group was injected with normal physiological saline subcutaneously for 2 days. The second group was injected with ISO at a dose of 85 mg/kg bwt subcutaneously for 2 days. The third, fourth and fifth groups were supplemented with ASX at doses of 10, 20, 30 mg/kg bwt, respectively daily by oral gavage for 21 days then injected with ISO dose of 85 mg/kg bwt subcutaneously for 2 successive days. Isoproterenol administration in rats elevated the activities of Creatine kinase‐MB (CK‐MB), aspartate transaminase (AST), lactate dehydrogenase (LDH), and other serum cardiac biomarkers Troponin‐I activities, oxidative stress biomarkers, malondialdehyde(MDA), Nuclear factor‐kappa B (NF‐KB), while it decreased Peroxisome proliferator‐activated receptor‐gamma coactivator (PGC‐1α), Nuclear factor erythroid‐2‐related factor 2 (Nfe212), mitochondrial transcriptional factor A (mt TFA), mitochondrial DNA copy number and glutathione system parameters. However, Astaxanthin decreased the activities of serum AST, LDH, CK‐MB, and Troponin I that elevated by ISO. In addition, it increased glutathione peroxidase and reductase activities, total glutathione and reduced GSH content, and GSH/GSSG ratio, mtDNA copy number, PGC‐1α expression and Tfam expression that improved mitochondrial biogenesis while it decreased GSSG and MDA contents and NF‐KB level in the cardiac tissues. This study indicated that astaxanthin relieved isoproterenol induced myocardial infarction via scavenging free radicals and reducing oxidative damage and apoptosis in cardiac tissue. [ABSTRACT FROM AUTHOR]

The cotton mealybug, Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae), is a significant economic pest with a global distribution. Despite the increasing volume of literature on mitochondrial genome sequencing, complete mitochondrial genome sequences have not been reported for P. solenopsis yet. Here, we assembled the complete mitochondrial genome of P. solenopsis using high throughput DNA sequencing technology. The genome is 14,831 bp in length and is comprised of 37 genes: 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and two ribosomal RNA (rRNA) genes. The total length of all PCGs is 9,678 bp, accounting for 65.2% of the overall mitogenome. Among the PCGs, atp8 is the smallest gene (99 bp) and nad5 is the largest (1,593 bp). Of the 13 PCGs, seven (nad3, cox3, atp6, atp8, cox2, cox1, nad2) are encoded on the majority strand (J-strand), while six (nad1, nad6, cob, nad4L, nad4, nad5) are on the minority strand (N-strand). The analysis revealed a predominant A+T base composition, making up 90.3% of the total genome. However, the non-coding regulatory control region (CR) is missing due to the non-overlapping endpoints of the linear assembly. This assembly provides comprehensive information for investigating the evolutionary relationships between scale insects and for the precise identification of insects. [ABSTRACT FROM AUTHOR]

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The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic di-nucleotide stimuli. Previous work showed an endoplasmic reticulum (ER) stress response, known as the unfolded protein response (UPR), activates STING. Herein, we sought to determine if ER stress generated a STING ligand, and to identify the UPR pathways involved. Induction of IFN-b expression following stimulation with the UPR inducer thapsigargin (TPG) or oxygen glucose deprivation required both STING and the dsDNA-sensing cyclic GMP-AMP synthase (cGAS). Furthermore, TPG increased cytosolic mitochondrial DNA, and immunofluorescence visualized dsDNA punctae in murine and human cells, providing a cGAS stimulus. N-acetylcysteine decreased IFN-b induction by TPG, implicating reactive oxygen species (ROS). However, mitoTEMPO, a mitochondrial oxidative stress inhibitor did not impact TPG-induced IFN. On the other hand, inhibiting the inositol requiring enzyme 1 (IRE1) ER stress sensor and its target transcription factor XBP1 decreased the generation of cytosolic dsDNA. iNOS upregulation was XBP1-dependent, and an iNOS inhibitor decreased cytosolic dsDNA and IFN-b, implicating ROS downstream of the IRE1-XBP1 pathway. Inhibition of the PKR-like ER kinase (PERK) pathway also attenuated cytoplasmic dsDNA release. The PERK-regulated apoptotic factor Bim was required for both dsDNA release and IFN-b mRNA induction. Finally, XBP1 and PERK pathways contributed to cytosolic dsDNA release and IFN-induction by the RNA virus, Vesicular Stomatitis Virus (VSV). Together, our findings suggest that ER stressors, including viral pathogens without nominal STING or cGAS ligands such as RNA viruses, trigger multiple canonical UPR pathways that cooperate to activate STING and downstream IFN-b via mitochondrial dsDNA release. [ABSTRACT FROM AUTHOR]

Saccharum complex includes genera Saccharum, Miscanthus, Erianthus, Narenga, and Tripidium. Since the Saccharum complex/Saccharinae constitutes the gene pool used by sugarcane breeders to introduce useful traits into sugarcane, studying the genomic characterization of the Saccharum complex has become particularly important. Here, we assembled graph-based mitochondrial genomes (mitogenomes) of four Saccharinae species (T. arundinaceum, E. rockii, M. sinensis, and N. porphyrocoma) using Illumina and PacBio sequencing data. The total lengths of the mitogenomes of T. arundinaceum, M. sinensis, E. rockii and N. porphyrocoma were 549,593 bp, 514,248 bp, 481,576 bp and 513,095 bp, respectively. Then, we performed a comparative mitogenomes analysis of Saccharinae species, including characterization, organelles transfer sequence, collinear sequence, phylogenetics analysis, and gene duplicated/loss. Our results provided the mitogenomes of four species closely related to sugarcane breeding, enriching the mitochondrial genomic resources of the Saccharinae. Additionally, our study offered new insights into the evolution of mitogenomes at the family and genus levels and enhanced our understanding of organelle evolution in the highly polyploid Saccharum genus. [ABSTRACT FROM AUTHOR]