Background Despite their low abundance in sperm, mitochondria have diverse functions in this cell type, includ-ing energy production, signalling and calcium regulation. In humans, sperm mitochondrial DNA content(mtDNA...Background Despite their low abundance in sperm, mitochondria have diverse functions in this cell type, includ-ing energy production, signalling and calcium regulation. In humans, sperm mitochondrial DNA content(mtDNAc) has been reported to be negatively linked to sperm function and fertility. Yet, the association between mtDNAc and sperm function in livestock remains unexplored. For this reason, this study aimed to shed some light on the link between mtDNAc and sperm function and fertilising potential in pigs. A qPCR method for mtDNAc quantification was optimised for pig sperm, and the association of this parameter with sperm motility, kinematics, mitochondrial activity, and fertility was subsequently interrogated.Results First, the q PCR method was found to be sensitive and efficient for mtDNAc quantification in pig sperm. By using this technique, mtDNAc was observed to be associated to sperm motility, mitochondrial activity and in vivo, but not in vitro, fertility outcomes. Specifically, sperm with low mtDNAc were seen to exhibit greater motility but decreased mitochondrial activity and intracellular reactive oxygen species. Interestingly, samples with lower mtD-NAc showed higher conception and farrowing rates, but similar in vitro fertilisation rates and embryo development, when compared to those with greater mtDNAc.Conclusions These findings enrich our comprehension of the association of mtDNAc with sperm biology, and lay the foundation for future research into employing this parameter as a molecular predictor for sperm function and fer-tility in livestock.展开更多
In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release f...In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.展开更多
Amphioctopus fangsiao(Cephalopoda:Octopodidae)is an important commercial species in the coastal waters of China.In recent years,however,the resource of A.fangsiao have declined because of habitat destruction and overf...Amphioctopus fangsiao(Cephalopoda:Octopodidae)is an important commercial species in the coastal waters of China.In recent years,however,the resource of A.fangsiao have declined because of habitat destruction and overfishing.To analyze the genetic variations of A.fangsiao caused by the fluctuation of resources,the population genetic structure of nine sampling locations collected from the Bohai Sea to the South China Sea were investigated,using mtDNA COI fragments and microsatellite DNA.The results of F-statistics,AMOVA,STRUCTURE and PCA analyses showed three phylogeographic clades(Clades A,B and C),revealing limited genetic exchange between north and south populations.These clades diverged in 2.23(Clades A and B)and 3.67(Clades A,B and C)million years ago,during the dramatic environmental fluctuations,such as sea level and temperature changes,have exerted great influence on the survival distribution pattern of global organisms.Our results for low genetic connectivity among A.fangsiao populations provide insights into the development of management strategies,that is,to manage this species as separate management unit.展开更多
BACKGROUND Here,we present a unique case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS)syndrome,which initially appeared to be autoimmune encephalitis and was ultimately confir...BACKGROUND Here,we present a unique case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS)syndrome,which initially appeared to be autoimmune encephalitis and was ultimately confirmed as MELAS with the mitochondrial DNA 3243A>G mutation.CASE SUMMARY A 58-year-old female presented with acute-onset speech impediment and auditory hallucinations,symmetrical bitemporal lobe abnormalities,clinical and laboratory findings,and a lack of relevant prodromal history,which suggested diagnosis of autoimmune encephalitis.Further work-up,in conjunction with the patient’s medical history,family history,and lactate peak on brain lesions on magnetic resonance imaging,suggested a mitochondrial disorder.Mitochondrial genome analysis revealed the m.3243A>G variant in the MT-TL1 gene,which led to a diagnosis of MELAS syndrome.CONCLUSION This case underscores the importance of considering MELAS as a potential cause of autoimmune encephalitis even if patients are over 40 years of age,as the symptoms and signs are atypical for MELAS syndrome.展开更多
BACKGROUND:Pulmonary fibrosis(PF)is one of the main causes of death in patients with paraquat(PQ)poisoning.This study aimed to evaluate the relationship between mitochondrial fi ssion and oxidative stress in PQ-induce...BACKGROUND:Pulmonary fibrosis(PF)is one of the main causes of death in patients with paraquat(PQ)poisoning.This study aimed to evaluate the relationship between mitochondrial fi ssion and oxidative stress in PQ-induced epithelial-mesenchymal transition(EMT)and PF.METHODS:C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro.Histological changes in the lungs were examined by hematoxylin and eosin(H&E)staining.Mitochondrial morphology was detected by MitoTracker®Deep Red FM or transmission electron microscopy(TEM).Western blotting and immunofluorescence were used to determine the expression of protein.The migration ability of the cells was detected by the cell scratch test.Mitochondrial DNA(mtDNA)levels were assessed by real-time polymerase chain reaction(PCR).Enzyme-linked immunosorbent assay(ELISA)was applied to detect cytokine levels.Superoxide dismutase(SOD)activity and the levels of glutathione(GSH)and malondialdehyde(MDA)were detected by chemichromatometry.RESULTS:PQ exposure caused EMT and PF in vivo and in vitro.PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1(Drp1),which were accompanied by oxidative stress.Inhibiting mitochondrial fission using mitochondrial division inhibitor-1(Mdivi-1),a selective inhibitor of Drp1,attenuated PQ-induced EMT and oxidative damage.Treatment with N-acetyl-L-cysteine(NAC),an antioxidant,reduced Drp1 expression,attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF.Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release,the expression of Toll-like receptor 9(TLR9)and phosphorylation(P)-NF-κB p65 as well as cytokines(interleukin 6[IL-6],interleukin-1β[IL-1β],and tumor necrosis factor-α[TNF-α])production.CONCLUSION:Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF,which is associated with the mtDNA/TLR9/NF-κB pathway.展开更多
Objective The study aimed to estimate the benchmark dose(BMD)of coke oven emissions(COEs)exposure based on mitochondrial damage with the mitochondrial DNA copy number(mtDNAcn)as a biomarker.Methods A total of 782 subj...Objective The study aimed to estimate the benchmark dose(BMD)of coke oven emissions(COEs)exposure based on mitochondrial damage with the mitochondrial DNA copy number(mtDNAcn)as a biomarker.Methods A total of 782 subjects were recruited,including 238 controls and 544 exposed workers.The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction.Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95%confidence lower limit(BMDL).Results The mtDNAcn of the exposure group was lower than that of the control group(0.60±0.29 vs.1.03±0.31;P<0.001).A dose-response relationship was shown between the mtDNAcn damage and COEs.Using the Benchmark Dose Software,the occupational exposure limits(OELs)for COEs exposure in males was 0.00190 mg/m^(3).The OELs for COEs exposure using the BBMD were 0.00170 mg/m^(3)for the total population,0.00158 mg/m^(3)for males,and 0.00174 mg/m^(3)for females.In possible risk obtained from animal studies(PROAST),the OELs of the total population,males,and females were 0.00184,0.00178,and 0.00192 mg/m^(3),respectively.Conclusion Based on our conservative estimate,the BMDL of mitochondrial damage caused by COEs is0.002 mg/m^(3).This value will provide a benchmark for determining possible OELs.展开更多
Accurate species identification is a key component of biodiversity research.DNA barcoding is an effective molecular method used for fish species identification.We aimed to study the DNA barcoding of fish in Zhoushan c...Accurate species identification is a key component of biodiversity research.DNA barcoding is an effective molecular method used for fish species identification.We aimed to study the DNA barcoding of fish in Zhoushan coastal waters,explore the differences and applicability of two gene fragments(12S rRNA and COI)of DNA barcoding in fish species identification,and established a comprehensive fish barcoding reference database.Two hundred and eighty-seven captured fish samples from Zhoushan coastal waters were identified using morphological characteristics and DNA barcoding.A total of 26412S rRNA sequences(belonging to eight orders,31 families,55 genera,and 66 species)and 188 COI sequences(belonging to seven orders,30 families,48 genera,and 58 species)were obtained.The lengths of the 12S rRNA sequences ranged from 165 to 178 bp,and the guanine-cytosine(GC)content was 45.37%.The average 12S rRNA interspecific and intraspecific genetic distances(K2P)were 0.10%and 26.66%,respectively.The length of the COI sequence ranged 574–655 bp,and the content of GC was 45.97%.The average 12S rRNA interspecific and intraspecific genetic distances(K2P)were 0.16%and 27.45%,respectively.The minimum interspecific genetic distances of 12S rRNA and COI(1.23%and 1.86%)were both greater than their maximum intraspecific genetic distances(2.42%and 8.66%).Three molecular analyses(NJ tree,ABGD,and GMYC)were performed to accurately identify and delineate species.Clustering errors occurred when the 12S rRNA sequences were delimited using the NJ tree method,and the delimitation results of ABGD and GMYC are consistent with the final species identification results.Our results demonstrate that DNA barcoding based on 12S rRNA and COI can be used as an effective tool for fish species identification,and 12S rRNA has good application prospects in the environmental DNA(eDNA)metabarcoding of marine fish.展开更多
In this study, the entire mitochondrial DNA(mtDNA) control region(CR) of Pholis fangi was amplified via polymerase chain reaction followed by direct sequencing. The length of the mtDNA CR consensus sequence of P. fang...In this study, the entire mitochondrial DNA(mtDNA) control region(CR) of Pholis fangi was amplified via polymerase chain reaction followed by direct sequencing. The length of the mtDNA CR consensus sequence of P. fangi was 853 bp in length. In accordance with the recognition sites as were previously reported in fish species, the mtDNA CR sequence of P. fangi can be divided into 3 domains, i.e., the extended terminal associated sequence(ETAS), the central conserved sequence block(CSB), and the CSB domain. In addition, the following structures were identified in the mtDNA CR sequence of P. fangi: 2 ETASs in the ETAS domain(TAS and cTAS), 6 CSBs in the central CSB domain(CSB-F to CSB-A), and 3 CSBs in the CSB domain(CSB-1 to CSB-3). These demonstrated that the structure of the mtDNA CR of P. fangi was substantially different from those of most other fish species. The mtDNA CR sequence of P. fangi contained one conserved region from 656 bp to 815 bp. Similar to most other fish species, P. fangi has no tandem repeat sequences in its mtDNA CR sequence. Phylogenetic analysis based on the complete mtDNA CR sequences showed that there were no genetic differences within P. fangi populations of the same geographical origin and between P. fangi populations of different geographical origins.展开更多
The mitochondrial theory of aging, a mainstream theory of aging which once included accumulation of mitochondrial DNA(mt DNA) damage by reactive oxygen species(ROS) as its cornerstone, has been increasingly losing gro...The mitochondrial theory of aging, a mainstream theory of aging which once included accumulation of mitochondrial DNA(mt DNA) damage by reactive oxygen species(ROS) as its cornerstone, has been increasingly losing ground and is undergoing extensive revision due to its inability to explain a growing body of emerging data. Concurrently, the notion of the central role for mtDNA in the aging process is being met with increased skepticism. Our progress in understanding the processes of mtDNA maintenance, repair, damage, and degradation in response to damage has largely refuted the view of mt DNA as being particularly susceptible to ROS-mediated mutagenesis due to its lack of "protective" histones and reduced complement of available DNA repair pathways. Recent research on mitochondrial ROS production has led to the appreciation that mitochondria, even in vitro, produce much less ROS than previously thought, automatically leading to a decreased expectation of physiologically achievable levels of mtDNA damage. New evidence suggests that both experimentally induced oxidative stress and radiation therapy result in very low levels of mtDNA mutagenesis. Recent advances provide evidence against the existence of the "vicious" cycle of mtDNA damage and ROS production. Meta-studies reveal no longevity benefit of increased antioxidant defenses. Simultaneously, exciting new observations from both comparative biology and experimental systems indicate that increased ROS production and oxidative damage to cellular macromolecules, including mtDNA, can be associated with extended longevity. A novel paradigm suggests that increased ROS production in aging may be the result of adaptive signaling rather than a detrimental byproduct of normal respiration that drives aging. Here, we review issues pertaining to the role of mtDNA in aging.展开更多
A molecular phylogenetic analysis of the genus Scomber was conducted based on mitochondrial(COI,Cyt b and control region) and nuclear(5S rDNA) DNA sequence data in multigene perspective.A variety of phylogenetic analy...A molecular phylogenetic analysis of the genus Scomber was conducted based on mitochondrial(COI,Cyt b and control region) and nuclear(5S rDNA) DNA sequence data in multigene perspective.A variety of phylogenetic analytic methods were used to clarify the current taxonomic classification and to assess phylogenetic relationships and the evolutionary history of this genus.The present study produced a well-resolved phylogeny that strongly supported the monophyly of Scomber.We confirmed that S.japonicus and S.colias were genetically distinct.Although morphologically and ecologically similar to S.colias,the molecular data showed that S.japonicus has a greater molecular affinity with S.australasicus,which conflicts with the traditional taxonomy.This phylogenetic pattern was corroborated by the mtDNA data,but incompletely by the nuclear DNA data.Phylogenetic concordance between the mitochondrial and nuclear DNA regions for the basal nodes supports an Atlantic origin for Scomber.The present-day geographic ranges of the species were compared with the resultant molecular phylogeny derived from partition Bayesian analyses of the combined data sets to evaluate possible dispersal routes of the genus.The present-day geographic distribution of Scomber species might be best ascribed to multiple dispersal events.In addition,our results suggest that phylogenies derived from multiple genes and long sequences exhibited improved phylogenetic resolution,from which we conclude that the phylogenetic reconstruction is a reliable representation of the evolutionary history of Scomber.展开更多
Two morphotypes of Plectropomus leopardus have been identified; morphometric and meristic analyses show that there is no diagnostic difference between them. A difference in color pattern was the most ap- propriate phe...Two morphotypes of Plectropomus leopardus have been identified; morphometric and meristic analyses show that there is no diagnostic difference between them. A difference in color pattern was the most ap- propriate phenotypic character with which to distinguish between the two morphotypes. Complete mito- chondrial DNA sequencing, however, indicated a clear difference between the two morphotypes. Barcoding analysis revealed no significant difference (P〉0.05) in CO1 or ND2 divergence among intramorphotypic individuals, even between geographically separated populations, whereas the intermorphotypic CO1 and ND2 divergences were large enough (averaging 0.95% for CO1 and 1.37% for ND2) to clearly discriminate between the two morphotypes. The color pattern difference, geographical distribution, together with the mtDNA and barcode sequencing data, suggest that the two morphotypes should be of two subspecies or even two species.展开更多
In the study, we present a fast, simple and inexpensive protocol for isolating chloroplast and mitochondrial DNA from one rapeseed leaf tissue sample. The chloroplast and mitochondria were separated from the same gree...In the study, we present a fast, simple and inexpensive protocol for isolating chloroplast and mitochondrial DNA from one rapeseed leaf tissue sample. The chloroplast and mitochondria were separated from the same green leaf tissue by differential centrifugations. The protocol is the first report that isolates plant chloroplast DNA (cpDNA) and mitochondrial DNA (mtDNA) from the same sample homogenate. The organelle DNA yield is 2-10 micrograms per gram of tissue; the DNA was fully restrictable and was successfully used for sequencing.展开更多
Objective: We report the results of Y-chromosomal profile and mtDNA (mitochondrial DNA) of the Chevalier Bayard (1476?-1524). Methods: His genomic DNA was extracted from a tooth of his mandible. His Y-STRs profile was...Objective: We report the results of Y-chromosomal profile and mtDNA (mitochondrial DNA) of the Chevalier Bayard (1476?-1524). Methods: His genomic DNA was extracted from a tooth of his mandible. His Y-STRs profile was obtained using the AmFirst identifier PCR amplification kit. The mtDNA genomic sequence intervals for HVR1 and HVR2 were amplified by PCR, with specific primers. Results: We obtained the complete STR (Short Tandem Repeats) profile, based on fourteen STRs (DYS19, DYS385.a, DYS389.I and .b, DYS390, DYS391, DYS392, DYS393, DYS438, DYS439, DYS448, DYS456 and DYS458 and Y-GATA-H4). The deduced Y-STRs profile corresponds to the sub-clade S21 of the major European haplogroup R1b-M269 (the “Germanic” haplotype). There are six mutations (16093C, 16211T and 16519C in the HVR1 sequence, 263G, 309.1C and 315.1C in the HVR2 sequence) in the mtDNA of Bayard. The 263G mutation determines the H mtDNA haplogroup and the 16211T suggests the H5 sub-clade of the H haplogroup (a sub-clade found at >8% frequency in France, at the periphery of the Alpine arch region). This sub-clade H5 (subsequently assimilated to the H10e haplotype) is that (with a perfect match) of a modern living male related (to 32 generations) to the Bayard maternal ascendance. The Bayard mtDNA haplotype was found once only in a database of 100 South-German mtDNA control sequences. Conclusions: The resulting R1b-M269 Y haplogroup established confirms the Germanic origin of the Bayard ancestors, suggested by genealogic studies concerning his paternal ascendance. The result concerning the mtDNA H10e haplotype found in the modern living male related to Bayard by matrilinear ascendance establishes that the DNA tooth is well of him, with a 99% of chance.展开更多
AIM: lo investigate the mutation in D-loop region of mitochondrial DNA in gastric cancer and its influence on the changes of reactive oxygen species (ROS) and cell cycle. METHODS: The D-loop region was amplified by PC...AIM: lo investigate the mutation in D-loop region of mitochondrial DNA in gastric cancer and its influence on the changes of reactive oxygen species (ROS) and cell cycle. METHODS: The D-loop region was amplified by PCR and sequenced. Reactive oxygen species and cell cycle were detected by flow cytometry in 20 specimens from gastriccancer and adjacent normal tissues. According to the sequence results, gastric cancer tissue was divided into mutation group and control group. Reactive oxygen species, apoptosis and proliferation in the two groups were compared.RESULTS: Among the 20 gastric cancer specimens, 18 mutations were identified in 7 patients, the mutation rate being 35%. There were four microsatellite instabilities in the mutations. No mutation was found in the adjacent tissues. Reactive oxygen species, apoptosis, and proliferation in the mutation group were all significantly higher than those in control group.CONCLUSION: Mutation in D-loop region plays a role in the genesis and development of gastric cancer.展开更多
Energy metabolism reprogramming was recently identified as one of the cancer hallmarks.One of the underlying mechanisms of energy metabolism reprogramming is mitochondrial dysfunction caused by mutations in nuclear ge...Energy metabolism reprogramming was recently identified as one of the cancer hallmarks.One of the underlying mechanisms of energy metabolism reprogramming is mitochondrial dysfunction caused by mutations in nuclear genes or mitochondrial DNA(mtDNA).In the past decades,several types of somatic mtDNA alterations have been identified in gastric cancer.However,the role of these mtDNA alterations in gastric cancer progression remains unclear.In this review,we summarize recently identified somatic mtDNA alterations in gastric cancers as well as the relationship between these alterations and the clinicopathological features of gastric cancer.The causative factors and potential roles of the somatic mtDNA alterations in cancer progression are also discussed.We suggest that point mutations and mtDNA copy number decreases are the two most common mtDNA alterations that result in mitochondrial dysfunction in gastric cancers.The two primary mutation types(transition mutations and mononucleotide or dinucleotide repeat instability)imply potential causative factors.Mitochondrial dysfunction-generated reactive oxygen species may be involved in the malignant changes of gastric cancer.The search for strategies to prevent mtDNA alterations and inhibit the mitochondrial retrograde signaling will benefit the development of novel treatments for gastric cancer and other malignancies.展开更多
Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the co...Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion.In diabetes mellitus,glycotoxicity,advanced oxidative stress,collagen cross-linking,and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction,which in turn further contributes to the oxidative damage of the diabetic vascular wall,endothelial dysfunc-tion,and atherosclerosis.展开更多
基金funded by the Ministry of Science and Innovation,Spain (AGL2017-88329-R, FPU18/00666 and PID2020-113320RB-I00)the Regional Government of Catalonia,Spain (2017-SGR-1229, 2020-FI-B-00412 and 2020-SGR-0900)the Catalan Institution for Research and Advanced Studies (ICREA)。
文摘Background Despite their low abundance in sperm, mitochondria have diverse functions in this cell type, includ-ing energy production, signalling and calcium regulation. In humans, sperm mitochondrial DNA content(mtDNAc) has been reported to be negatively linked to sperm function and fertility. Yet, the association between mtDNAc and sperm function in livestock remains unexplored. For this reason, this study aimed to shed some light on the link between mtDNAc and sperm function and fertilising potential in pigs. A qPCR method for mtDNAc quantification was optimised for pig sperm, and the association of this parameter with sperm motility, kinematics, mitochondrial activity, and fertility was subsequently interrogated.Results First, the q PCR method was found to be sensitive and efficient for mtDNAc quantification in pig sperm. By using this technique, mtDNAc was observed to be associated to sperm motility, mitochondrial activity and in vivo, but not in vitro, fertility outcomes. Specifically, sperm with low mtDNAc were seen to exhibit greater motility but decreased mitochondrial activity and intracellular reactive oxygen species. Interestingly, samples with lower mtD-NAc showed higher conception and farrowing rates, but similar in vitro fertilisation rates and embryo development, when compared to those with greater mtDNAc.Conclusions These findings enrich our comprehension of the association of mtDNAc with sperm biology, and lay the foundation for future research into employing this parameter as a molecular predictor for sperm function and fer-tility in livestock.
基金supported by the National Natural Science Foundation of China,No.81971269 (to DP)the Science and Technology Commission of Shanghai,No.YDZX20213100001003 (to DP)。
文摘In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.
基金The National Natural Science Foundation of China under contract Nos 32170536 and 31672257。
文摘Amphioctopus fangsiao(Cephalopoda:Octopodidae)is an important commercial species in the coastal waters of China.In recent years,however,the resource of A.fangsiao have declined because of habitat destruction and overfishing.To analyze the genetic variations of A.fangsiao caused by the fluctuation of resources,the population genetic structure of nine sampling locations collected from the Bohai Sea to the South China Sea were investigated,using mtDNA COI fragments and microsatellite DNA.The results of F-statistics,AMOVA,STRUCTURE and PCA analyses showed three phylogeographic clades(Clades A,B and C),revealing limited genetic exchange between north and south populations.These clades diverged in 2.23(Clades A and B)and 3.67(Clades A,B and C)million years ago,during the dramatic environmental fluctuations,such as sea level and temperature changes,have exerted great influence on the survival distribution pattern of global organisms.Our results for low genetic connectivity among A.fangsiao populations provide insights into the development of management strategies,that is,to manage this species as separate management unit.
基金Supported by the Science and Technology Plan of Jinhua City,No.2020-3-026。
文摘BACKGROUND Here,we present a unique case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS)syndrome,which initially appeared to be autoimmune encephalitis and was ultimately confirmed as MELAS with the mitochondrial DNA 3243A>G mutation.CASE SUMMARY A 58-year-old female presented with acute-onset speech impediment and auditory hallucinations,symmetrical bitemporal lobe abnormalities,clinical and laboratory findings,and a lack of relevant prodromal history,which suggested diagnosis of autoimmune encephalitis.Further work-up,in conjunction with the patient’s medical history,family history,and lactate peak on brain lesions on magnetic resonance imaging,suggested a mitochondrial disorder.Mitochondrial genome analysis revealed the m.3243A>G variant in the MT-TL1 gene,which led to a diagnosis of MELAS syndrome.CONCLUSION This case underscores the importance of considering MELAS as a potential cause of autoimmune encephalitis even if patients are over 40 years of age,as the symptoms and signs are atypical for MELAS syndrome.
基金supported by the Wenzhou Municipal Science and Technology Bureau(Y2020092)partly by the Key Specialty of Traditional Chinese Medicine of Zhejiang Province in the 13th Five-Year Plan period(Emergency Department).
文摘BACKGROUND:Pulmonary fibrosis(PF)is one of the main causes of death in patients with paraquat(PQ)poisoning.This study aimed to evaluate the relationship between mitochondrial fi ssion and oxidative stress in PQ-induced epithelial-mesenchymal transition(EMT)and PF.METHODS:C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro.Histological changes in the lungs were examined by hematoxylin and eosin(H&E)staining.Mitochondrial morphology was detected by MitoTracker®Deep Red FM or transmission electron microscopy(TEM).Western blotting and immunofluorescence were used to determine the expression of protein.The migration ability of the cells was detected by the cell scratch test.Mitochondrial DNA(mtDNA)levels were assessed by real-time polymerase chain reaction(PCR).Enzyme-linked immunosorbent assay(ELISA)was applied to detect cytokine levels.Superoxide dismutase(SOD)activity and the levels of glutathione(GSH)and malondialdehyde(MDA)were detected by chemichromatometry.RESULTS:PQ exposure caused EMT and PF in vivo and in vitro.PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1(Drp1),which were accompanied by oxidative stress.Inhibiting mitochondrial fission using mitochondrial division inhibitor-1(Mdivi-1),a selective inhibitor of Drp1,attenuated PQ-induced EMT and oxidative damage.Treatment with N-acetyl-L-cysteine(NAC),an antioxidant,reduced Drp1 expression,attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF.Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release,the expression of Toll-like receptor 9(TLR9)and phosphorylation(P)-NF-κB p65 as well as cytokines(interleukin 6[IL-6],interleukin-1β[IL-1β],and tumor necrosis factor-α[TNF-α])production.CONCLUSION:Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF,which is associated with the mtDNA/TLR9/NF-κB pathway.
基金supported by the National Natural Science Foundation of China[grant numbers:NSFC81872597,81001239]。
文摘Objective The study aimed to estimate the benchmark dose(BMD)of coke oven emissions(COEs)exposure based on mitochondrial damage with the mitochondrial DNA copy number(mtDNAcn)as a biomarker.Methods A total of 782 subjects were recruited,including 238 controls and 544 exposed workers.The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction.Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95%confidence lower limit(BMDL).Results The mtDNAcn of the exposure group was lower than that of the control group(0.60±0.29 vs.1.03±0.31;P<0.001).A dose-response relationship was shown between the mtDNAcn damage and COEs.Using the Benchmark Dose Software,the occupational exposure limits(OELs)for COEs exposure in males was 0.00190 mg/m^(3).The OELs for COEs exposure using the BBMD were 0.00170 mg/m^(3)for the total population,0.00158 mg/m^(3)for males,and 0.00174 mg/m^(3)for females.In possible risk obtained from animal studies(PROAST),the OELs of the total population,males,and females were 0.00184,0.00178,and 0.00192 mg/m^(3),respectively.Conclusion Based on our conservative estimate,the BMDL of mitochondrial damage caused by COEs is0.002 mg/m^(3).This value will provide a benchmark for determining possible OELs.
基金Supported by the Zhejiang Provincial Key Research and Development Program (No.2021C02047)。
文摘Accurate species identification is a key component of biodiversity research.DNA barcoding is an effective molecular method used for fish species identification.We aimed to study the DNA barcoding of fish in Zhoushan coastal waters,explore the differences and applicability of two gene fragments(12S rRNA and COI)of DNA barcoding in fish species identification,and established a comprehensive fish barcoding reference database.Two hundred and eighty-seven captured fish samples from Zhoushan coastal waters were identified using morphological characteristics and DNA barcoding.A total of 26412S rRNA sequences(belonging to eight orders,31 families,55 genera,and 66 species)and 188 COI sequences(belonging to seven orders,30 families,48 genera,and 58 species)were obtained.The lengths of the 12S rRNA sequences ranged from 165 to 178 bp,and the guanine-cytosine(GC)content was 45.37%.The average 12S rRNA interspecific and intraspecific genetic distances(K2P)were 0.10%and 26.66%,respectively.The length of the COI sequence ranged 574–655 bp,and the content of GC was 45.97%.The average 12S rRNA interspecific and intraspecific genetic distances(K2P)were 0.16%and 27.45%,respectively.The minimum interspecific genetic distances of 12S rRNA and COI(1.23%and 1.86%)were both greater than their maximum intraspecific genetic distances(2.42%and 8.66%).Three molecular analyses(NJ tree,ABGD,and GMYC)were performed to accurately identify and delineate species.Clustering errors occurred when the 12S rRNA sequences were delimited using the NJ tree method,and the delimitation results of ABGD and GMYC are consistent with the final species identification results.Our results demonstrate that DNA barcoding based on 12S rRNA and COI can be used as an effective tool for fish species identification,and 12S rRNA has good application prospects in the environmental DNA(eDNA)metabarcoding of marine fish.
基金supported by the Public Science and Technology Research Funds Projects of Ocean (Nos. 201305043 and 201405010)
文摘In this study, the entire mitochondrial DNA(mtDNA) control region(CR) of Pholis fangi was amplified via polymerase chain reaction followed by direct sequencing. The length of the mtDNA CR consensus sequence of P. fangi was 853 bp in length. In accordance with the recognition sites as were previously reported in fish species, the mtDNA CR sequence of P. fangi can be divided into 3 domains, i.e., the extended terminal associated sequence(ETAS), the central conserved sequence block(CSB), and the CSB domain. In addition, the following structures were identified in the mtDNA CR sequence of P. fangi: 2 ETASs in the ETAS domain(TAS and cTAS), 6 CSBs in the central CSB domain(CSB-F to CSB-A), and 3 CSBs in the CSB domain(CSB-1 to CSB-3). These demonstrated that the structure of the mtDNA CR of P. fangi was substantially different from those of most other fish species. The mtDNA CR sequence of P. fangi contained one conserved region from 656 bp to 815 bp. Similar to most other fish species, P. fangi has no tandem repeat sequences in its mtDNA CR sequence. Phylogenetic analysis based on the complete mtDNA CR sequences showed that there were no genetic differences within P. fangi populations of the same geographical origin and between P. fangi populations of different geographical origins.
基金Supported by The National Institutes of Health grants No.ES03456,PO1 HL66299,and No.OD010944
文摘The mitochondrial theory of aging, a mainstream theory of aging which once included accumulation of mitochondrial DNA(mt DNA) damage by reactive oxygen species(ROS) as its cornerstone, has been increasingly losing ground and is undergoing extensive revision due to its inability to explain a growing body of emerging data. Concurrently, the notion of the central role for mtDNA in the aging process is being met with increased skepticism. Our progress in understanding the processes of mtDNA maintenance, repair, damage, and degradation in response to damage has largely refuted the view of mt DNA as being particularly susceptible to ROS-mediated mutagenesis due to its lack of "protective" histones and reduced complement of available DNA repair pathways. Recent research on mitochondrial ROS production has led to the appreciation that mitochondria, even in vitro, produce much less ROS than previously thought, automatically leading to a decreased expectation of physiologically achievable levels of mtDNA damage. New evidence suggests that both experimentally induced oxidative stress and radiation therapy result in very low levels of mtDNA mutagenesis. Recent advances provide evidence against the existence of the "vicious" cycle of mtDNA damage and ROS production. Meta-studies reveal no longevity benefit of increased antioxidant defenses. Simultaneously, exciting new observations from both comparative biology and experimental systems indicate that increased ROS production and oxidative damage to cellular macromolecules, including mtDNA, can be associated with extended longevity. A novel paradigm suggests that increased ROS production in aging may be the result of adaptive signaling rather than a detrimental byproduct of normal respiration that drives aging. Here, we review issues pertaining to the role of mtDNA in aging.
基金Supported by the International Cooperation and Exchange of the National Natural Science Foundation of China (No. 31061160187)Special Fund for Agro-scientific Research in the Public Interest(No. 200903005)
文摘A molecular phylogenetic analysis of the genus Scomber was conducted based on mitochondrial(COI,Cyt b and control region) and nuclear(5S rDNA) DNA sequence data in multigene perspective.A variety of phylogenetic analytic methods were used to clarify the current taxonomic classification and to assess phylogenetic relationships and the evolutionary history of this genus.The present study produced a well-resolved phylogeny that strongly supported the monophyly of Scomber.We confirmed that S.japonicus and S.colias were genetically distinct.Although morphologically and ecologically similar to S.colias,the molecular data showed that S.japonicus has a greater molecular affinity with S.australasicus,which conflicts with the traditional taxonomy.This phylogenetic pattern was corroborated by the mtDNA data,but incompletely by the nuclear DNA data.Phylogenetic concordance between the mitochondrial and nuclear DNA regions for the basal nodes supports an Atlantic origin for Scomber.The present-day geographic ranges of the species were compared with the resultant molecular phylogeny derived from partition Bayesian analyses of the combined data sets to evaluate possible dispersal routes of the genus.The present-day geographic distribution of Scomber species might be best ascribed to multiple dispersal events.In addition,our results suggest that phylogenies derived from multiple genes and long sequences exhibited improved phylogenetic resolution,from which we conclude that the phylogenetic reconstruction is a reliable representation of the evolutionary history of Scomber.
基金Key Program of the Science and Technology Department Foundation of Fujian Province under contract No.2007N0050the Seed Industry Innovation and Industrialization Project of Fujian Province,China(on the subtopic of groupers)
文摘Two morphotypes of Plectropomus leopardus have been identified; morphometric and meristic analyses show that there is no diagnostic difference between them. A difference in color pattern was the most ap- propriate phenotypic character with which to distinguish between the two morphotypes. Complete mito- chondrial DNA sequencing, however, indicated a clear difference between the two morphotypes. Barcoding analysis revealed no significant difference (P〉0.05) in CO1 or ND2 divergence among intramorphotypic individuals, even between geographically separated populations, whereas the intermorphotypic CO1 and ND2 divergences were large enough (averaging 0.95% for CO1 and 1.37% for ND2) to clearly discriminate between the two morphotypes. The color pattern difference, geographical distribution, together with the mtDNA and barcode sequencing data, suggest that the two morphotypes should be of two subspecies or even two species.
基金the Ministry of Agriculture of China Genetically Modified Organisms Breeding Major Projects (2009ZX08009-018B)
文摘In the study, we present a fast, simple and inexpensive protocol for isolating chloroplast and mitochondrial DNA from one rapeseed leaf tissue sample. The chloroplast and mitochondria were separated from the same green leaf tissue by differential centrifugations. The protocol is the first report that isolates plant chloroplast DNA (cpDNA) and mitochondrial DNA (mtDNA) from the same sample homogenate. The organelle DNA yield is 2-10 micrograms per gram of tissue; the DNA was fully restrictable and was successfully used for sequencing.
文摘Objective: We report the results of Y-chromosomal profile and mtDNA (mitochondrial DNA) of the Chevalier Bayard (1476?-1524). Methods: His genomic DNA was extracted from a tooth of his mandible. His Y-STRs profile was obtained using the AmFirst identifier PCR amplification kit. The mtDNA genomic sequence intervals for HVR1 and HVR2 were amplified by PCR, with specific primers. Results: We obtained the complete STR (Short Tandem Repeats) profile, based on fourteen STRs (DYS19, DYS385.a, DYS389.I and .b, DYS390, DYS391, DYS392, DYS393, DYS438, DYS439, DYS448, DYS456 and DYS458 and Y-GATA-H4). The deduced Y-STRs profile corresponds to the sub-clade S21 of the major European haplogroup R1b-M269 (the “Germanic” haplotype). There are six mutations (16093C, 16211T and 16519C in the HVR1 sequence, 263G, 309.1C and 315.1C in the HVR2 sequence) in the mtDNA of Bayard. The 263G mutation determines the H mtDNA haplogroup and the 16211T suggests the H5 sub-clade of the H haplogroup (a sub-clade found at >8% frequency in France, at the periphery of the Alpine arch region). This sub-clade H5 (subsequently assimilated to the H10e haplotype) is that (with a perfect match) of a modern living male related (to 32 generations) to the Bayard maternal ascendance. The Bayard mtDNA haplotype was found once only in a database of 100 South-German mtDNA control sequences. Conclusions: The resulting R1b-M269 Y haplogroup established confirms the Germanic origin of the Bayard ancestors, suggested by genealogic studies concerning his paternal ascendance. The result concerning the mtDNA H10e haplotype found in the modern living male related to Bayard by matrilinear ascendance establishes that the DNA tooth is well of him, with a 99% of chance.
文摘AIM: lo investigate the mutation in D-loop region of mitochondrial DNA in gastric cancer and its influence on the changes of reactive oxygen species (ROS) and cell cycle. METHODS: The D-loop region was amplified by PCR and sequenced. Reactive oxygen species and cell cycle were detected by flow cytometry in 20 specimens from gastriccancer and adjacent normal tissues. According to the sequence results, gastric cancer tissue was divided into mutation group and control group. Reactive oxygen species, apoptosis and proliferation in the two groups were compared.RESULTS: Among the 20 gastric cancer specimens, 18 mutations were identified in 7 patients, the mutation rate being 35%. There were four microsatellite instabilities in the mutations. No mutation was found in the adjacent tissues. Reactive oxygen species, apoptosis, and proliferation in the mutation group were all significantly higher than those in control group.CONCLUSION: Mutation in D-loop region plays a role in the genesis and development of gastric cancer.
基金Supported by A grant from the Center of Excellence for Cancer Research at Taipei Veterans General,the Ministry of Health and Welfare,No.DOH102-TDC-111-007,Executive Yuana grant from the Ministry of Education,Aim for the Top University Planand grant from the National Science Council,No.NSC101-2320-B-010-068-MY3,Taiwan
文摘Energy metabolism reprogramming was recently identified as one of the cancer hallmarks.One of the underlying mechanisms of energy metabolism reprogramming is mitochondrial dysfunction caused by mutations in nuclear genes or mitochondrial DNA(mtDNA).In the past decades,several types of somatic mtDNA alterations have been identified in gastric cancer.However,the role of these mtDNA alterations in gastric cancer progression remains unclear.In this review,we summarize recently identified somatic mtDNA alterations in gastric cancers as well as the relationship between these alterations and the clinicopathological features of gastric cancer.The causative factors and potential roles of the somatic mtDNA alterations in cancer progression are also discussed.We suggest that point mutations and mtDNA copy number decreases are the two most common mtDNA alterations that result in mitochondrial dysfunction in gastric cancers.The two primary mutation types(transition mutations and mononucleotide or dinucleotide repeat instability)imply potential causative factors.Mitochondrial dysfunction-generated reactive oxygen species may be involved in the malignant changes of gastric cancer.The search for strategies to prevent mtDNA alterations and inhibit the mitochondrial retrograde signaling will benefit the development of novel treatments for gastric cancer and other malignancies.
基金Supported by The Russian Ministry of Science and Education
文摘Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion.In diabetes mellitus,glycotoxicity,advanced oxidative stress,collagen cross-linking,and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction,which in turn further contributes to the oxidative damage of the diabetic vascular wall,endothelial dysfunc-tion,and atherosclerosis.