scholarly journals Mitochondrial DNA Copy Number and Developmental Origins of Health and Disease (DOHaD)

2021 ◽  
Vol 22 (12) ◽  
pp. 6634
Author(s):  
Hisanori Fukunaga
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Copy Number ◽  
Surrogate Marker ◽  
Epidemiological Studies ◽  
Copy Number Variations ◽  
Fetal Life ◽  
Mtdna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Health And Disease

Mitochondrial dysfunction is known to contribute to mitochondrial diseases, as well as to a variety of aging-based pathologies. Mitochondria have their own genomes (mitochondrial DNA (mtDNA)) and the abnormalities, such as point mutations, deletions, and copy number variations, are involved in mitochondrial dysfunction. In recent years, several epidemiological studies and animal experiments have supported the Developmental Origin of Health and Disease (DOHaD) theory, which states that the environment during fetal life influences the predisposition to disease and the risk of morbidity in adulthood. Mitochondria play a central role in energy production, as well as in various cellular functions, such as apoptosis, lipid metabolism, and calcium metabolism. In terms of the DOHaD theory, mtDNA copy number may be a mediator of health and disease. This paper summarizes the results of recent epidemiological studies on the relationship between environmental factors and mtDNA copy number during pregnancy from the perspective of DOHaD theory. The results of these studies suggest a hypothesis that mtDNA copy number may reflect environmental influences during fetal life and possibly serve as a surrogate marker of health risks in adulthood.

Abstract 751: Lung mitochondrial DNA copy number variations: E-cig users, smokers, and never-smokers

2021 ◽  
Author(s):  
Kellie M. Mori ◽  
Joseph P. McElroy ◽  
Daniel Y. Weng ◽  
Sangwoon Chung ◽  
Sarah A. Reisinger ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Copy Number Variations ◽  
Dna Copy Number ◽  
Dna Copy Number Variations ◽  
Mitochondrial Dna Copy Number ◽  
Never Smokers

Abstract 271: Mitochondrial DNA Copy Number in Peripheral Blood Cells is Associated With All -Cause Mortality in Older Cardiovascular Patients

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Oxana Galenko ◽  
James Juan ◽  
Benjamin D Horne ◽  
Stacey Knight ◽  
John F Carlquist
Keyword(s):  
Mitochondrial Dna ◽  
Mortality Risk ◽  
Copy Number ◽  
Cox Regression ◽  
Surrogate Marker ◽  
Cellular Damage ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Cardiovascular Patients ◽  
All Cause Mortality

Background: Mitochondrial DNA copy number (Mt CN) is a surrogate marker of mitochondrial function. Variations in Mt CN have been associated with several age-related diseases. Lower Mt CN may indicate impaired cellular energy production whereas higher Mt CN may compensate for energy disbalance but also may lead to cellular damage through oxidative stress. This study evaluated the association of Mt CN and all-cause mortality in older cardiovascular patients (Pt). Methods: The study was approved by the Intermountain Healthcare Institutional Review Board. Consenting subjects (n=2,253) were participants in the INSPIRE registry undergoing cardiac catheterization at the Intermountain Heart Institute. Total DNA was extracted from EDTA stabilized blood with either Puregene (Qiagen) or Reliaprep (Promega) reagents. Relative Mt CN measurements were performed with multiplexed real-time polymerase chain reaction coamplifying a stable site of Mt D- Loop and a region of a single copy nuclear β-2-microglobulin gene(β2M) and calculated as a ratio of Mt to β2M DNA. Cox regression was used to evaluate the association of Mt CN with all-cause mortality, with adjustment considering 32 covariables. Further adjustment entered the Intermountain Risk Score (IMRS), a validated mortality risk predictor. Results: Mean Pt age was age 62.3±13.8 yrs.; 65.2% were male; 1,122 (50%) died during 25.4 years of follow-up. Mt CN was lower for males (539±449 vs 654 ± 1053 for females; p=0.004). Mt CN was 616±917 in decedents and 542±438 in survivors (p=0.014). In univariable Cox regression, Quartile 1 versus Quartile 4 of Mt CN was associated with the highest mortality risk (hazard ratio [HR]=1.45, CI=1.22, 1.71, p<0.001). This association remained significant after multivariable adjustment (HR=1.30, CI=1.10, 1.54, p=0.003). There was minimal correlation between IMRS and Mt CN continuous values (r= -0.09 for males, r= -0.13 for females). In Cox regression, adjustment for IMRS and covariables showed Mt CN remained associated with mortality (HR=1.30, CI=1.08, 1.57, p=0.006). Conclusions: Low Mt CN is independently associated with higher risk of all-cause mortality. Further studies validating this finding and examining potential underlying physiologic protective mechanisms may prove to be of therapeutic and prognostic value.

scholarly journals Thinking outside the nucleus: Mitochondrial DNA copy number in health and disease

Mitochondrion ◽  
2020 ◽  
Vol 53 ◽  
pp. 214-223 ◽  
Author(s):  
Christina A. Castellani ◽  
Ryan J. Longchamps ◽  
Jing Sun ◽  
Eliseo Guallar ◽  
Dan E. Arking
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Health And Disease

264 MITOCHONDRIAL DNA COPY NUMBER IN OOCYTES OF PREPUBERTAL AND CYCLIC GILTS

2011 ◽  
Vol 23 (1) ◽  
pp. 230
Author(s):  
P. Pawlak ◽  
E. Pers-Kamczyc ◽  
D. Lechniak-Cieslak
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Blastocyst Stage ◽  
Developmental Competence ◽  
Published Data ◽  
Mtdna Copy Number ◽  
Final Size ◽  
Domestic Species ◽  
Mitochondrial Dna Copy Number ◽  
Wide Range

In many domestic species (pig, cow, sheep), oocytes from prepubertal females show impaired quality when compared with those from adult animals. Incomplete cytoplasmic maturation is thought to be the main factor responsible for reduced developmental competence of embryos derived from prepubertal oocytes. The status of ooplasm maturation is also reflected by the copy number of mitochondrial DNA (mtDNA). Because replication of mtDNA ceases when oocytes reach their final size and occurs again at the blastocyst stage, the mtDNA copy number is a proved marker of oocyte quality in the pig (El Shourbagy et al. 2006 Reproduction 131, 233–245). The number of mtDNA copies in the grown oocyte is crucial to sustain the first embryonic divisions. To increase the rate of good-quality blastocysts, oocytes of domestic animals have been evaluated by the brilliant cresyl blue test (BCB). According to El Shourbagy et al. (2006), more competent BCB+ oocytes possess higher copy number of mtDNA (on average 222 446) than do their BCB– counterparts (115 352). However, there are no published data on the variation in mtDNA copy number in oocytes derived from ovaries of prepubertal (NCL) and cyclic (CL) gilts. Ovaries of NCL and CL gilts were collected in a local slaughterhouse. Cumulus–oocyte complexes (COC) were aspirated from nonatretic follicles 2 to 6 mm in diameter and evaluated morphologically. Only COC with a proper morphology were subjected to the BCB test. A group of non-BCB-treated COC served as control. Four groups of COC were collected: BCB+ (CL, NCL) and control (CL, NCL). Follicular cells attached to oocytes were removed by pipetting, and completely denuded gametes were individually frozen in liquid nitrogen. Analysis of the mtDNA copy number included isolation of the total DNA followed by amplification of the Cytochrome b (CYTB) gene by real-time PCR (one copy per one mitochondrial genome). Differences in mtDNA copy number among experimental groups were evaluated by Student’s t-test. To date, 30 BCB+ oocytes have been analysed individually (15 CL and 15 NCL). The analysed parameter varied in a wide range from 79 852 to 522 712 copies in CL oocytes and from 52 270 to 287 852 copies in NCL oocytes. Oocytes from cyclic gilts contained significantly more mtDNA copies (on average 267 524) than did gametes of prepubertal females (179 339; P < 0.05). The data on the mtDNA copy number in the control oocytes are currently under investigation. The preliminary results indicate that impaired oocytes quality of prepubertal gilts may be also attributed to the reduced copy number of mtDNA. This project was sponsored by MSHE Poland (grant no. 451/N-COST/2009/0).

scholarly journals Mitochondrial DNA copy number and diabetes: the Atherosclerosis Risk in Communities (ARIC) study

2020 ◽  
Vol 8 (1) ◽  
pp. e001204
Author(s):  
Bailey DeBarmore ◽  
Ryan J Longchamps ◽  
Yiyi Zhang ◽  
Rita R Kalyani ◽  
Eliseo Guallar ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Copy Number ◽  
Buffy Coat ◽  
Incident Diabetes ◽  
Atherosclerosis Risk In Communities ◽  
Mitochondrial Dna Copy Number ◽  
Atherosclerosis Risk ◽  
Aric Study

IntroductionMitochondrial DNA copy number (mtDNA-CN) is a measure of mitochondrial dysfunction and is associated with diabetes in experimental models. To explore the temporality of mitochondrial dysfunction and diabetes, we estimated the prevalent and incident association of mtDNA-CN and diabetes.Research design and methodsWe assessed the associations of mtDNA-CN measured from buffy coat with prevalent and incident diabetes, stratified by race, in 8954 white and 2444 black participants in the Atherosclerosis Risk in Communities (ARIC) study, an observational cohort study. Follow-up for incident analyses was complete through visit 6, 2016.ResultsMean age at mtDNA-CN measurement was 57 years and 59% were female. Prevalence of diabetes at time of mtDNA-CN measurement was higher in blacks (563/2444, 23%) than whites (855/8954, 10%). The fully adjusted odds of prevalent diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.05 (95% CI 0.74 to 1.49) among black and 1.49 (95% CI 1.20 to 1.85) among white participants. Over a median follow-up time of 19 years (Q1, Q3: 11, 24 years), we observed 617 incident diabetes cases among 1744 black and 2121 cases among 7713 white participants free of diabetes at baseline. The fully adjusted hazard of incident diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.07 (95% CI 0.84 to 1.38) among black and 0.97 (95% CI 0.86 to 1.10) among white participants.ConclusionsLower mtDNA-CN in buffy coat was associated with prevalent diabetes in white but not black ARIC participants. Lower mtDNA-CN was not associated with incident diabetes over 20 years of follow-up in whites or blacks.

scholarly journals Social integration predicts mitochondrial DNA copy number in rhesus macaques

2018 ◽  
Author(s):  
Reena Debray ◽  
Noah Snyder-Mackler ◽  
Jordan Kohn ◽  
Mark Wilson ◽  
Luis Barreiro ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Social Stress ◽  
Copy Number ◽  
Rhesus Macaques ◽  
Dominance Rank ◽  
Low Rank ◽  
Mtdna Copy Number ◽  
Dna Copy Number ◽  
Chronic Social Stress ◽  
Mitochondrial Dna Copy Number

AbstractIn many social mammals, social adversity predicts compromised health and reduced fitness. These effects are thought to be driven in part by chronic social stress, but their molecular underpinnings are not well understood. Recent work suggests that chronic stress can affect mitochondrial copy number, heteroplasmy rates, and function. Here, we tested the first two possibilities, for the first time in nonhuman primates. We manipulated dominance rank in captive female rhesus macaques (n=45), where low rank induces chronic social stress, and measured mitochondrial DNA copy number and heteroplasmy in five peripheral blood mononuclear cell types from each study subject. We found no effect of dominance rank on either mtDNA copy number or heteroplasmy rates. However, grooming rates, a measure of affiliative social behavior predicted by high social status, was positively associated with mtDNA copy number in B cells, cytotoxic T cells, and monocytes. Our results suggest that social interactions can influence mtDNA regulation in immune cells. Further, they indicate the importance of considering both affiliative and competitive interactions in investigating this relationship.

scholarly journals Mitochondrial DNA Copy Number Variation Across Human Cancers

2015 ◽  
Author(s):  
Ed Reznik ◽  
Martin Miller ◽  
Yasin Senbabaoglu ◽  
Nadeem Riaz ◽  
William Lee ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number Variation ◽  
Copy Number ◽  
Large Scale ◽  
Tumor Type ◽  
Mtdna Copy Number ◽  
Tissue Samples ◽  
Mitochondrial Dna Copy Number ◽  
Number Variation ◽  
Tumor Types

In cancer, mitochondrial dysfunction, through mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), contributes to the malignant transformation and progression of tumors. Here, we report the first large-scale survey of mtDNA copy number variation across 21 distinct solid tumor types, examining over 13,000 tissue samples profiled with next-generation sequencing methods. We find a tendency for cancers, especially of the bladder and kidney, to be significantly depleted of mtDNA, relative to matched normal tissue. We show that mtDNA copy number is correlated to the expression of mitochondrially-localized metabolic pathways, suggesting that mtDNA copy number variation reflect gross changes in mitochondrial metabolic activity. Finally, we identify a subset of tumor-type-specific somatic alterations, including IDH1 and NF1 mutations in gliomas, whose incidence is strongly correlated to mtDNA copy number. Our findings suggest that modulation of mtDNA copy number may play a role in the pathology of cancer.

scholarly journals Concurrent Measurement of Mitochondrial DNA Copy Number and ATP Concentration in Single Bovine Oocytes

2021 ◽  
Vol 4 (4) ◽  
pp. 88
Author(s):  
Casey C. Read ◽  
Sadikshya Bhandari ◽  
Sarah E. Moorey
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Germinal Vesicle ◽  
Mtdna Copy Number ◽  
Dna Copy Number ◽  
Metabolic Substrates ◽  
Metabolic Outcomes ◽  
Atp Concentration ◽  
Mitochondrial Dna Copy Number ◽  
Bovine Oocytes

To sustain energy-demanding developmental processes, oocytes must accumulate adequate stores of metabolic substrates and mitochondrial numbers prior to the initiation of maturation. In the past, researchers have utilized pooled samples to study oocyte metabolism, and studies that related multiple metabolic outcomes in single oocytes, such as ATP concentration and mitochondrial DNA copy number, were not possible. Such scenarios decreased sensitivity to intraoocyte metabolic relationships and made it difficult to obtain adequate sample numbers during studies with limited oocyte availability. Therefore, we developed and validated procedures to measure both mitochondrial DNA (mtDNA) copy number and ATP quantity in single oocytes. Validation of our procedures revealed that we could successfully divide oocyte lysates into quarters and measure consistent results from each of the aliquots for both ATP and mtDNA copy number. Coefficient of variation between the values retrieved for mtDNA copy number and ATP quantity quadruplicates were 4.72 ± 0.98 and 1.61 ± 1.19, respectively. We then utilized our methodology to concurrently measure mtDNA copy number and ATP quantity in germinal vesicle (GV) and metaphase two (MII) stage oocytes. Our methods revealed a significant increase in ATP levels (GV = 628.02 ± 199.53 pg, MII = 1326.24 ± 199.86 pg, p < 0.001) and mtDNA copy number (GV = 490,799.4 ± 544,745.9 copies, MII = 1,087,126.9 ± 902,202.8 copies, p = 0.035) in MII compared to GV stage oocytes. This finding is consistent with published literature and provides further validation of the accuracy of our methods. The ability to produce consistent readings and expected results from aliquots of the lysate from a single oocyte reveals the sensitivity and feasibility of using this method.

scholarly journals Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome

2022 ◽  
Vol 44 (1) ◽  
pp. 273-287
Author(s):  
Amira Podolak ◽  
Joanna Liss ◽  
Jolanta Kiewisz ◽  
Sebastian Pukszta ◽  
Celina Cybulska ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Human Reproduction ◽  
Preimplantation Embryos ◽  
Human Embryos ◽  
Embryo Morphology ◽  
Cleavage Stage ◽  
Mtdna Copy Number ◽  
Developmental Potential ◽  
Mitochondrial Dna Copy Number

A retrospective case control study was undertaken at the molecular biology department of a private center for reproductive medicine in order to determine whether any correlation exists between mitochondrial DNA (mtDNA) content of cleavage-stage preimplantation embryos and their developmental potential. A total of 69 couples underwent IVF treatment (averaged women age: 36.5, SD 4.9) and produced a total of 314 embryos. A single blastomere was biopsied from each embryo at the cleavage stage (day-3 post-fertilization) subjected to low-pass next generation sequencing (NGS), for the purpose of detecting aneuploidy. For each sample, the number of mtDNA reads obtained after analysis using NGS was divided by the number of reads attributable to the nuclear genome. The mtDNA copy number amount was found to be higher in aneuploid embryos than in those that were euploid (mean mtDNA ratio ± SD: 6.3 ± 7.5 versus 7.1 ± 5.8, p < 0.004; U Mann–Whitney test), whereas no statistically significant differences in mtDNA content were seen in relation to embryo morphology (6.6 ± 4.8 vs. 8.5 ± 13.6, p 0.09), sex (6.6 ± 4.1 vs. 6.2 ± 6.8, p 0.16), maternal age (6.9 ± 7.8 vs. 6.7 ± 4.5, p 0.14) or its ability to implant (7.4 ± 6.6 vs. 5.1 ± 4.6, p 0.18). The mtDNA content cannot serve as a useful biomarker at this point in development. However, further studies investigating both quantitative and qualitative aspects of mtDNA are still required to fully evaluate the relationship between mitochondrial DNA and human reproduction.

scholarly journals Mitochondrial DNA Copy Number in Peripheral Blood Is Independently Associated with Visceral Fat Accumulation in Healthy Young Adults

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jee-Yon Lee ◽  
Duk-Chul Lee ◽  
Jee-Aee Im ◽  
Ji-Won Lee
Keyword(s):  
Young Adults ◽  
Mitochondrial Dna ◽  
Visceral Fat ◽  
Copy Number ◽  
Visceral Obesity ◽  
Mtdna Copy Number ◽  
Metabolic Disturbances ◽  
Visceral Fat Area ◽  
Mitochondrial Dna Copy Number ◽  
Increased Risk

Aims. Visceral obesity is associated with an increased risk of cardiometabolic diseases and it is important to identify the underlying mechanisms. There is growing evidence that mitochondrial dysfunction is associated with metabolic disturbances related to visceral obesity. In addition, maintaining mitochondrial DNA (mtDNA) copy number is important for preserving mitochondrial function. Therefore, we investigated the relationship between mtDNA copy number and visceral fat in healthy young adults.Methods. A total of 94 healthy young subjects were studied. Biomarkers of metabolic risk factors were assessed along with body composition by computed tomography. mtDNA copy number was measured in peripheral leukocytes using real-time polymerase chain reaction (PCR) methods.Results. The mtDNA copy number correlated with BMI (r=-0.22,P=0.04), waist circumference (r=-0.23,P=0.03), visceral fat area (r=-0.28,P=-0.01), HDL-cholesterol levels (r=0.25,P=0.02), and hs-CRP (r=0.32,P=0.02) after adjusting for age and sex. Both stepwise and nonstepwise multiple regression analyses confirmed that visceral fat area was independently associated with mtDNA copy number (β=-0.33,P<0.01,β=0.32, andP=0.03, resp.).Conclusions. An independent association between mtDNA content and visceral adiposity was identified. These data suggest that mtDNA copy number is a potential predictive marker for metabolic disturbances. Further studies are required to understand the causality and clinical significance of our findings.

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