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1.
Trop Anim Health Prod ; 53(5): 512, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637013

RESUMO

NOVELTY STATEMENT: The present study was conducted for the first time in Pakistan to investigate Cytochrome C Oxidase Subunit 1 (CO1) gene and full-length Displacement Loop (D-loop) region of mitochondrial DNA in Azi-Kheli buffalo breed native to northern hilly areas of Khyber Pakhtunkhwa Province of Pakistan. The present study was designed to investigate phylogeny and diversity in Azi-Kheli buffalo, through two mitochondrial DNA regions, i.e., Cytochrome C Oxidase Subunit-I (CO1) and Displacement Loop (D-loop) region. Thirty (30) blood samples were taken from Azi-Kheli pure breed animals from original breeding tract, i.e., Khwazakhela, Swat. Polymerase chain reactions using gene-specific primers were carried out for amplifying 709-bp region of CO1 gene and 1159-bp region of D-Loop for identification, phylogeny, and diversity in Azi-Kheli buffalo, respectively. The sequences of CO1 gene revealed four (04) haplotypes, whereas D-loop sequences revealed five (05) haplotypes. Mean interspecific diversity with related species was 2.56%, and mean intraspecific diversity within Azi-Kheli buffalo was 0.25%, estimated via Kimura-2 parameter. Phylogenetic tree (maximum likelihood) revealed clustering of Azi-Kheli haplotypes with river buffalo and is distinct from swamp buffalo and other related species of genus Bubalus. Mean haplotype and nucleotide diversity of D-loop were Hd = 0.9601 ± SD = 0.096 and π = 0.01208 ± SD = 0.00182, respectively. Phylogenetic tree (neighbor-joining) revealed two main clades, i.e., river buffalo and swamp buffalo clade. The haplotypes of Azi-Kheli clustered with haplotypes of different river buffalo breeds at different positions. The current study suggests that Azi-Kheli has common origin with other river buffalo breeds; hence, it is river buffalo which harbors high genetic diversity.


Assuntos
Búfalos , Variação Genética , Animais , Búfalos/genética , DNA Mitocondrial/genética , Haplótipos , Filogenia
2.
BMC Genomics ; 22(1): 746, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654361

RESUMO

BACKGROUND: Skeletonema species are prominent primary producers, some of which can also cause massive harmful algal blooms (HABs) in coastal waters under specific environmental conditions. Nevertheless, genomic information of Skeletonema species is currently limited, hindering advanced research on their role as primary producers and as HAB species. Mitochondrial genome (mtDNA) has been extensively used as "super barcode" in the phylogenetic analyses and comparative genomic analyses. However, of the 21 accepted Skeletonema species, full-length mtDNAs are currently available only for a single species, S. marinoi. RESULTS: In this study, we constructed full-length mtDNAs for six strains of five Skeletonema species, including S. marinoi, S. tropicum, S. grevillei, S. pseudocostatum and S. costatum (with two strains), which were isolated from coastal waters in China. The mtDNAs of all of these Skeletonema species were compact with short intergenic regions, no introns, and no repeat regions. Comparative analyses of these Skeletonema mtDNAs revealed high conservation, with a few discrete regions of high variations, some of which could be used as molecular markers for distinguishing Skeletonema species and for tracking the biogeographic distribution of these species with high resolution and specificity. We estimated divergence times among these Skeletonema species using 34 mtDNAs genes with fossil data as calibration point in PAML, which revealed that the Skeletonema species formed the independent clade diverging from Thalassiosira species approximately 48.30 Mya. CONCLUSIONS: The availability of mtDNAs of five Skeletonema species provided valuable reference sequences for further evolutionary studies including speciation time estimation and comparative genomic analysis among diatom species. Divergent regions could be used as molecular markers for tracking different Skeletonema species in the fields of coastal regions.


Assuntos
Diatomáceas , Genoma Mitocondrial , DNA Mitocondrial , Diatomáceas/genética , Proliferação Nociva de Algas , Filogenia
3.
BMC Genomics ; 22(1): 736, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641784

RESUMO

BACKGROUND: Reference sequences play a vital role in next-generation sequencing (NGS), impacting mapping quality during genome analyses. However, reference genomes usually do not represent the full range of genetic diversity of a species as a result of geographical divergence and independent demographic events of different populations. For the mitochondrial genome (mitogenome), which occurs in high copy numbers in cells and is strictly maternally inherited, an optimal reference sequence has the potential to make mitogenome alignment both more accurate and more efficient. In this study, we used three different types of reference sequences for mitogenome mapping, i.e., the commonly used reference sequence (CU-ref), the breed-specific reference sequence (BS-ref) and the sample-specific reference sequence (SS-ref), respectively, and compared the accuracy of mitogenome alignment and SNP calling among them, for the purpose of proposing the optimal reference sequence for mitochondrial DNA (mtDNA) analyses of specific populations RESULTS: Four pigs, representing three different breeds, were high-throughput sequenced, subsequently mapping reads to the reference sequences mentioned above, resulting in a largest mapping ratio and a deepest coverage without increased running time when aligning reads to a BS-ref. Next, single nucleotide polymorphism (SNP) calling was carried out by 18 detection strategies with the three tools SAMtools, VarScan and GATK with different parameters, using the bam results mapping to BS-ref. The results showed that all eighteen strategies achieved the same high specificity and sensitivity, which suggested a high accuracy of mitogenome alignment by the BS-ref because of a low requirement for SNP calling tools and parameter choices. CONCLUSIONS: This study showed that different reference sequences representing different genetic relationships to sample reads influenced mitogenome alignment, with the breed-specific reference sequences being optimal for mitogenome analyses, which provides a refined processing perspective for NGS data.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , Animais , DNA Mitocondrial/genética , Análise de Sequência de DNA , Suínos/genética
5.
J Assoc Physicians India ; 69(9): 11-12, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34585887

RESUMO

INTRODUCTION: Although metabolic surgery has been shown to offer beneficial primary outcome results in obese individuals / obese Type 2 diabetes mellitus (T2DM) patients, there is paucity of information on the underlying mechanisms. In the recent years, estimations of non-invasive molecular parameters viz., telomere length and mtDNA copy number (mtDNAcn) assume significance as robust biomarkers. However, there is lack of evidence about this especially, in the Indian context. To assess the changes in the telomere length and mtDNAcn levels after metabolic surgery in obese Asian Indians with dysglycemia along with routine measurements of anthropometry, glycemic/lipidimic parameters and inflammatory markers. METHODS: This study is a prospective one-year follow-up study of 16 obese individuals with dysglycemia who underwent metabolic surgery at a tertiary diabetes centre in South India. Telomere length, mtDNAcn, serum adiponectin, glycated haemoglobin and high- sensitivity C-reactive protein (hs-CRP) levels were analysed before surgery and at 6 and 12 months after surgery. RESULTS: There was a significant reduction in weight (p<0.001), BMI (p<0.001), waist circumference (p<0.001), fasting and postprandial glucose (p<0.05), HbA1c (p<0.001), triglycerides (p<0.05), hs CRP (p<0.05) and increase in serum adiponectin (p<0.05) at 6 and 12 months post-surgery compared to the preoperative status. There was a significant reduction in mtDNAcn (p<0.001) and a significant increase in telomere length (p<0.001) at 6 and 12 months post metabolic surgery. CONCLUSION: We report an increase in telomere length and decrease in circulatory mtDNA copy number levels at 6 and 12 months post metabolic surgery in obese individuals with T2DM in India.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , DNA Mitocondrial/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Seguimentos , Humanos , Obesidade/complicações , Obesidade/genética , Estudos Prospectivos , Telômero/genética
6.
Medicina (Kaunas) ; 57(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34577851

RESUMO

Background and Objectives. The importance of mitochondria in inflammatory pathologies, besides providing energy, is associated with the release of mitochondrial damage products, such as mitochondrial DNA (mt-DNA), which may perpetuate inflammation. In this review, we aimed to show the importance of mitochondria, as organelles that produce energy and intervene in multiple pathologies, focusing mainly in COVID-19 and using multiple molecular mechanisms that allow for the replication and maintenance of the viral genome, leading to the exacerbation and spread of the inflammatory response. The evidence suggests that mitochondria are implicated in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which forms double-membrane vesicles and evades detection by the cell defense system. These mitochondrion-hijacking vesicles damage the integrity of the mitochondrion's membrane, releasing mt-DNA into circulation and triggering the activation of innate immunity, which may contribute to an exacerbation of the pro-inflammatory state. Conclusions. While mitochondrial dysfunction in COVID-19 continues to be studied, the use of mt-DNA as an indicator of prognosis and severity is a potential area yet to be explored.


Assuntos
COVID-19 , DNA Mitocondrial , DNA Mitocondrial/genética , Humanos , Imunidade Inata , Mitocôndrias/genética , SARS-CoV-2
7.
BMC Bioinformatics ; 22(1): 417, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470617

RESUMO

BACKGROUND: Variation in mitochondrial DNA (mtDNA) identified by genotyping microarrays or by sequencing only the hypervariable regions of the genome may be insufficient to reliably assign mitochondrial genomes to phylogenetic lineages or haplogroups. This lack of resolution can limit functional and clinical interpretation of a substantial body of existing mtDNA data. To address this limitation, we developed and evaluated a large, curated reference alignment of complete mtDNA sequences as part of a pipeline for imputing missing mtDNA single nucleotide variants (mtSNVs). We call our reference alignment and pipeline MitoImpute. RESULTS: We aligned the sequences of 36,960 complete human mitochondrial genomes downloaded from GenBank, filtered and controlled for quality. These sequences were reformatted for use in imputation software, IMPUTE2. We assessed the imputation accuracy of MitoImpute by measuring haplogroup and genotype concordance in data from the 1000 Genomes Project and the Alzheimer's Disease Neuroimaging Initiative (ADNI). The mean improvement of haplogroup assignment in the 1000 Genomes samples was 42.7% (Matthew's correlation coefficient = 0.64). In the ADNI cohort, we imputed missing single nucleotide variants. CONCLUSION: These results show that our reference alignment and panel can be used to impute missing mtSNVs in existing data obtained from using microarrays, thereby broadening the scope of functional and clinical investigation of mtDNA. This improvement may be particularly useful in studies where participants have been recruited over time and mtDNA data obtained using different methods, enabling better integration of early data collected using less accurate methods with more recent sequence data.


Assuntos
DNA Mitocondrial , Polimorfismo de Nucleotídeo Único , DNA Mitocondrial/genética , Frequência do Gene , Genoma Humano , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Filogenia
8.
Nat Commun ; 12(1): 5241, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475388

RESUMO

Individual induced pluripotent stem cells (iPSCs) show considerable phenotypic heterogeneity, but the reasons for this are not fully understood. Comprehensively analysing the mitochondrial genome (mtDNA) in 146 iPSC and fibroblast lines from 151 donors, we show that most age-related fibroblast mtDNA mutations are lost during reprogramming. However, iPSC-specific mutations are seen in 76.6% (108/141) of iPSC lines at a mutation rate of 8.62 × 10-5/base pair. The mutations observed in iPSC lines affect a higher proportion of mtDNA molecules, favouring non-synonymous protein-coding and tRNA variants, including known disease-causing mutations. Analysing 11,538 single cells shows stable heteroplasmy in sub-clones derived from the original donor during differentiation, with mtDNA variants influencing the expression of key genes involved in mitochondrial metabolism and epidermal cell differentiation. Thus, the dynamic mtDNA landscape contributes to the heterogeneity of human iPSCs and should be considered when using reprogrammed cells experimentally or as a therapy.


Assuntos
Reprogramação Celular/genética , DNA Mitocondrial/genética , Mutação/genética , Adulto , Idoso , Senescência Celular/genética , Feminino , Fibroblastos , Expressão Gênica , Genoma Mitocondrial/genética , Heteroplasmia/genética , Humanos , Células-Tronco Pluripotentes Induzidas , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360765

RESUMO

Mitochondria, often referred to as the powerhouses of cells, are vital organelles that are present in almost all eukaryotic organisms, including humans. They are the key energy suppliers as the site of adenosine triphosphate production, and are involved in apoptosis, calcium homeostasis, and regulation of the innate immune response. Abnormalities occurring in mitochondria, such as mitochondrial DNA (mtDNA) mutations and disturbances at any stage of mitochondrial RNA (mtRNA) processing and translation, usually lead to severe mitochondrial diseases. A fundamental line of investigation is to understand the processes that occur in these organelles and their physiological consequences. Despite substantial progress that has been made in the field of mtRNA processing and its regulation, many unknowns and controversies remain. The present review discusses the current state of knowledge of RNA processing in human mitochondria and sheds some light on the unresolved issues.


Assuntos
Mitocôndrias/metabolismo , Processamento Pós-Transcricional do RNA , RNA Mitocondrial/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Humanos , Mitocôndrias/genética , RNA Mitocondrial/genética
10.
FASEB J ; 35(9): e21864, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34423880

RESUMO

Resistance training (RT) dynamically alters the skeletal muscle nuclear DNA methylome. However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older, Caucasian untrained males (65 ± 7 y.o.) performed six weeks of full-body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 h following the last RT session. Vastus lateralis (VL) biopsies were also obtained. VL DNA was subjected to reduced representation bisulfite sequencing providing excellent coverage across the ~16-kilobase mtDNA methylome (254 CpG sites). Biochemical assays were also performed, and older male data were compared to younger trained males (22 ± 2 y.o., n = 7, n = 6 Caucasian & n = 1 African American). RT increased whole-body lean tissue mass (p = .017), VL thickness (p = .012), and knee extensor torque (p = .029) in older males. RT also affected the mtDNA methylome, as 63% (159/254) of the CpG sites demonstrated reduced methylation (p < .05). Several mtDNA sites presented a more "youthful" signature in older males after RT in comparison to younger males. The 1.12 kilobase mtDNA D-loop/control region, which regulates replication and transcription, possessed enriched hypomethylation in older males following RT. Enhanced expression of mitochondrial H- and L-strand genes and complex III/IV protein levels were also observed (p < .05). While limited to a shorter-term intervention, this is the first evidence showing that RT alters the mtDNA methylome in skeletal muscle. Observed methylome alterations may enhance mitochondrial transcription, and RT evokes mitochondrial methylome profiles to mimic younger men. The significance of these findings relative to broader RT-induced epigenetic changes needs to be elucidated.


Assuntos
Envelhecimento , Metilação de DNA , DNA Mitocondrial/metabolismo , Epigenoma , Regulação da Expressão Gênica , Genes Mitocondriais/genética , Músculo Esquelético/metabolismo , Treinamento de Força , Idoso , Envelhecimento/genética , Envelhecimento/metabolismo , DNA Mitocondrial/genética , Humanos , Masculino , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Músculo Esquelético/citologia , RNA Mensageiro/análise , RNA Mensageiro/genética , Adulto Jovem
11.
Anal Chem ; 93(33): 11592-11600, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34383484

RESUMO

Breast cancer 1 gene (BRCA1) DNA mutations impact skeletal muscle functions. Inducible skeletal muscle specific Brca1 homozygote knockout (Brca1KOsmi, KO) mice accumulate mitochondrial DNA (mtDNA) mutations resulting in loss of muscle quality.1 Complementary electrochemical andmass spectrometry analyses were utilized to rapidly assess mtDNA or nuclear DNA (nDNA) extracted directly from mouse skeletal muscles. Oxidative peak currents (Ip) from DNA immobilized layer by layer (LbL) were monitored using square-wave voltammetry (SWV) via Ru(bpy)32+ electrocatalysis. Ip significantly decreased (p < 0.05) for KO mtDNA compared to heterozygous KO (Het) or wild type (WT), indicative of decreases in the guanine content. nDNA Ip significantly increased in KO compared to WT (p < 0.05), suggesting an accumulation of damaged nDNA. Guanine or oxidatively damaged guanine content was monitored via appropriate m/z mass transitions using liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Guanine in both KO mtDNA and nDNA was significantly lower, while oxidatively damaged guanine in KO nDNA was significantly elevated versus WT. These data demonstrate a loss of guanine content consistent with mtDNA mutation accumulation. Oxidative damage in KO nDNA suggests that repair processes associated with Brca1 are impacted. Overall, electrochemical and LC-MS/MS analysis can provide chemical-level answers to biological model phenotypic responses as a rapid and cost-effective analysis alternative to established assays.


Assuntos
Genes BRCA1 , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida , DNA Mitocondrial/genética , Camundongos , Músculo Esquelético
12.
Fa Yi Xue Za Zhi ; 37(3): 358-365, 2021 Jun.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34379905

RESUMO

Abstract: Objective To study the genetic polymorphism of whole mitochondrial DNA (mtDNA) genomes in She population in Zhejiang and to explore the maternal genetic structure of the She population. Methods Whole mtDNA genomes of 231 unrelated individuals from She population in Zhejiang Province were sequenced. The number of mutations and population genetics parameters such as, the haplotype diversity (HD), discrimination power (DP), and random match probabilities (RMP) were analyzed. The mtDNA haplogroups of Zhejiang She population were classified, and the maternal genetic relationships between She and nine other Chinese populations were estimated. Results In 231 Zhejiang She samples, 8 507 mutations (702 types) were observed and the samples were classified into 94 haplogroups. The HD, DP and RMP values were 0.998 6, 0.994 2 and 0.005 8, respectively. The lowest genetic differentiation degree (Fst=0.006 89) was detected between Zhejiang She population and southern Han population. Principal component analysis (PCA) and median-joining network analysis showed that the genetic distance of Zhejiang She population with Guangxi Yao, Yunnan Dai and Southern Han populations was relatively close, but the population still had some unique genetic characteristics. Conclusion The whole mtDNA genomes are highly polymorphic in Zhejiang She population. The Zhejiang She population contains complex and diverse genetic components and has a relatively close maternal genetic relationship with Guangxi Yao, Yunnan Dai and Southern Han populations. Meanwhile, Zhejiang She population has kept its unique maternal genetic components.


Assuntos
DNA Mitocondrial , Sequenciamento de Nucleotídeos em Larga Escala , Grupo com Ancestrais do Continente Asiático/genética , China , DNA Mitocondrial/genética , Grupos Étnicos/genética , Feminino , Genética Populacional , Haplótipos , Humanos , Polimorfismo Genético
14.
Gene ; 802: 145868, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364911

RESUMO

The Honduran white bat, Ectophylla alba (Allen 1982), is one of eight species belonging to the family Phyllostomidae that exclusively roosts in tents. Due to its restricted distribution, habitat specificity, and diet requirements, E. alba has been strongly affected by habitat loss and fragmentation during the last decade. In this study, we developed the first genomic resource for this species; we assembled and analyzed in detail the complete mitochondrial genome of E. alba. The mitogenome of E. alba is 16,664 bp in length and is comprised of 13 protein coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA genes (tRNAs), and a putative Control Region (CR) 1,232 bp in length. Gene arrangement in the mitochondrial chromosome of E. alba is identical to that reported before in other species of co-familiar bats. All PCGs are under purifying selection, with atp8 experiencing the least selective pressure. In all PCGs, codons ending with adenine are preferred over others ending in thymine and cytosine. Except tRNA-Serine 1, all tRNAs exhibit a cloverleaf secondary structure. The CR of E. alba exhibits three domains commonly described in other mammals, including bats; extended terminal associated sequences (ETAS), central, and conserved sequence block (CSB). A ML phylogenetic reconstruction of the family Phyllostomidae based on all 13 mitochondrial PCGs confirms the monophyletic status of the subfamily Sternodermatinae and indicates the close relationship between E. alba and the genus Artibeus. This is the first genomic resource developed for E. alba and represents the first step to improving our understanding of the genomic underpinnings involved in the evolution of specialization as well as acclimatization and adaptation to local and global change of specialist bats.


Assuntos
Quirópteros/genética , Genoma Mitocondrial , Animais , Quirópteros/classificação , Uso do Códon , DNA Mitocondrial , Filogenia , Proteínas/genética , RNA de Transferência/genética
15.
Int J Mol Sci ; 22(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34445229

RESUMO

Symbiosis between the mitochondrion and the ancestor of the eukaryotic cell allowed cellular complexity and supported life. Mitochondria have specialized in many key functions ensuring cell homeostasis and survival. Thus, proper communication between mitochondria and cell nucleus is paramount for cellular health. However, due to their archaebacterial origin, mitochondria possess a high immunogenic potential. Indeed, mitochondria have been identified as an intracellular source of molecules that can elicit cellular responses to pathogens. Compromised mitochondrial integrity leads to release of mitochondrial content into the cytosol, which triggers an unwanted cellular immune response. Mitochondrial nucleic acids (mtDNA and mtRNA) can interact with the same cytoplasmic sensors that are specialized in recognizing genetic material from pathogens. High-energy demanding cells, such as neurons, are highly affected by deficits in mitochondrial function. Notably, mitochondrial dysfunction, neurodegeneration, and chronic inflammation are concurrent events in many severe debilitating disorders. Interestingly in this context of pathology, increasing number of studies have detected immune-activating mtDNA and mtRNA that induce an aberrant production of pro-inflammatory cytokines and interferon effectors. Thus, this review provides new insights on mitochondria-driven inflammation as a potential therapeutic target for neurodegenerative and primary mitochondrial diseases.


Assuntos
Mitocôndrias/imunologia , Doenças Neurodegenerativas/imunologia , Animais , Citocinas/imunologia , DNA Mitocondrial/imunologia , Humanos , Mitocôndrias/patologia , Doenças Neurodegenerativas/patologia , RNA Mitocondrial/imunologia
16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 225-229, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374231

RESUMO

Objective: To investigate the relationship between mitochondrial DNA (mtDNA) variation and high altitude essential hypertension(HAEH) in the Chinese Tajik population. Methods: Fifty-three patients with HAEH and 46 healthy subjects were enrolled from the Chinese Tajik population. The mtDNA fragments were amplificated by polymerase chain reaction, and products were sequenced to acquire full sequence of mtDNA. The mtDNA sequences of all subjects were compared to the Cambridge sequence to explore mtDNA variations and analyze difference between HAEH and healthy controls. Online softwares were applied to predict function changes caused by positive associated mtDNA variations. Results: Compared to the control group, the frequency of haplogroup U4b was significant higher in HAEH group(P=0.023,OR=7.062,CI(95%)=1.306-38.182), and the frequencies of 8 mutations from haplogroup U4b showed a significant difference between the HAEH group and control group (all with P values below 0.05). The mt DNA15693T>C mutation was the only missense mutation, which affected amino acid 316 in mitochondrial cytochrome b (MTCYB) by changing it from methionine to threonine. Bioinformatics analysis indicated that the mutation in MTCYB may play a biological role through affecting the second structure of protein. Conclusion: MtDNA subhaplogroup U4b is a genetic factor for HAEH in the Chinese Tajik population, and mtDNA15693T>C mutation may be an important molecular mechanism of HAEH.


Assuntos
DNA Mitocondrial , Predisposição Genética para Doença , Altitude , Grupo com Ancestrais do Continente Asiático/genética , China , DNA Mitocondrial/genética , Hipertensão Essencial/genética , Haplótipos , Humanos , Mutação
17.
Zh Nevrol Psikhiatr Im S S Korsakova ; 121(7. Vyp. 2): 62-64, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34387448

RESUMO

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by autoimmune inflammation, demyelination, and neurodegeneration. MS is a complex disease that develops under the influence of environmental factors in genetically predisposed individuals. Currently, more than 200 genetic loci associated with MS have been identified by various methods. Some of them are located in the mitochondrial DNA. This paper collects data on mtDNA variants associated with MS in the Russian ethnic group, and shows the possibility of using this information to construct and refine models for predicting the development of MS.


Assuntos
Genoma Mitocondrial , Esclerose Múltipla , DNA Mitocondrial/genética , Predisposição Genética para Doença , Humanos , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único
18.
Elife ; 102021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34343089

RESUMO

Poly(ADP-ribose) polymerase (PARP) enzymes initiate (mt)DNA repair mechanisms and use nicotinamide adenine dinucleotide (NAD+) as energy source. Prolonged PARP activity can drain cellular NAD+ reserves, leading to de-regulation of important molecular processes. Here, we provide evidence of a pathophysiological mechanism that connects mtDNA damage to cardiac dysfunction via reduced NAD+ levels and loss of mitochondrial function and communication. Using a transgenic model, we demonstrate that high levels of mice cardiomyocyte mtDNA damage cause a reduction in NAD+ levels due to extreme DNA repair activity, causing impaired activation of NAD+-dependent SIRT3. In addition, we show that myocardial mtDNA damage in combination with high dosages of nicotinamideriboside (NR) causes an inhibition of sirtuin activity due to accumulation of nicotinamide (NAM), in addition to irregular cardiac mitochondrial morphology. Consequently, high doses of NR should be used with caution, especially when cardiomyopathic symptoms are caused by mitochondrial dysfunction and instability of mtDNA.


Assuntos
Reparo do DNA , DNA Mitocondrial/metabolismo , Cardiopatias/fisiopatologia , Coração/fisiopatologia , Miocárdio/metabolismo , NAD/metabolismo , Animais , Dano ao DNA , Células HeLa , Humanos , Camundongos , Mitocôndrias/metabolismo , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Niacinamida/metabolismo , Compostos de Piridínio/efeitos adversos , Sirtuínas/antagonistas & inibidores
19.
DNA Cell Biol ; 40(9): 1131-1143, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34370602

RESUMO

Besides being powerhouses of the cell, mitochondria released into extracellular space act as intercellular signaling. Mitochondria and their components mediate cell-to-cell communication in free form or embedded in a carrier. The pathogenesis of cardiovascular disease is complex, which shows close relationship with inflammation and metabolic abnormalities. Since mitochondria sustain optimal function of the heart, extracellular mitochondria are emerging as a key regulator in the development of cardiovascular disease. In this review, we provide recent findings in the presence and forms of mitochondria transfer between cells, as well as the effects of these mitochondria on vascular inflammation and ischemic myocardium. Mitochondrial transplantation is a novel treatment paradigm for patients suffering from acute cardiovascular accident and challenges the traditional methods of mitochondria isolation.


Assuntos
Doenças Cardiovasculares/metabolismo , Inflamação/metabolismo , Mitocôndrias/metabolismo , Animais , Comunicação Celular , DNA Mitocondrial/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Transdução de Sinais
20.
Nat Cell Biol ; 23(8): 870-880, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34341532

RESUMO

The memory of stresses experienced by parents can be passed on to descendants as a forecast of the challenges to come. Here, we discovered that the neuronal mitochondrial perturbation-induced systemic mitochondrial unfolded protein response (UPRmt) in Caenorhabditis elegans can be transmitted to offspring over multiple generations. The transgenerational activation of UPRmt is mediated by maternal inheritance of elevated levels of mitochondrial DNA (mtDNA), which causes the proteostasis stress within mitochondria. Furthermore, results from intercrossing studies using wild C. elegans strains further support that maternal inheritance of higher levels of mtDNA can induce the UPRmt in descendants. The mitokine Wnt signalling pathway is required for the transmission of elevated mtDNA levels across generations, thereby conferring lifespan extension and stress resistance to offspring. Collectively, our results reveal that the nervous system can transmit stress signals across generations by increasing mtDNA in the germline, enabling descendants to better cope with anticipated challenges.


Assuntos
Proteínas de Caenorhabditis elegans/genética , DNA Mitocondrial/metabolismo , Genes Mitocondriais , Herança Materna , Neurônios/metabolismo , Estresse Fisiológico/genética , Resposta a Proteínas não Dobradas/genética , Células HEK293 , Humanos , Longevidade/genética , Biogênese de Organelas , Via de Sinalização Wnt
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