scholarly journals Changes in Mitochondrial Genome Associated with Predisposition to Atherosclerosis and Related Disease

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 377 ◽  
Author(s):  
Aleksandrina Volobueva ◽  
Andrey Grechko ◽  
Shaw-Fang Yet ◽  
Igor Sobenin ◽  
Alexander Orekhov
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Molecular Markers ◽  
Cardiovascular Diseases ◽  
Mitochondrial Genome ◽  
Therapeutic Intervention ◽  
Molecular Mechanisms ◽  
Disease Pathogenesis ◽  
Mtdna Mutations ◽  
Related Disease

Atherosclerosis-related cardiovascular diseases remain the leading cause of morbidity and mortality, and the search for novel diagnostic and therapeutic methods is ongoing. Mitochondrial DNA (mtDNA) mutations associated with atherosclerosis represent one of the less explored aspects of the disease pathogenesis that may bring some interesting opportunities for establishing novel molecular markers and, possibly, new points of therapeutic intervention. Recent studies have identified a number of mtDNA mutations, for which the heteroplasmy level was positively or negatively associated with atherosclerosis, including the disease at its early, subclinical stages. In this review, we summarize the results of these studies, providing a list of human mtDNA mutations potentially involved in atherosclerosis. The molecular mechanisms underlying such involvement remain to be elucidated, although it is likely that some of them may be responsible for the increased oxidative stress, which plays an important role in atherosclerosis.

scholarly journals The Role of Mitochondrial DNA Mutations in Cardiovascular Diseases

2022 ◽  
Vol 23 (2) ◽  
pp. 952
Author(s):  
Siarhei A. Dabravolski ◽  
Victoria A. Khotina ◽  
Vasily N. Sukhorukov ◽  
Vladislav A. Kalmykov ◽  
Liudmila M. Mikhaleva ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Mitochondrial Proteins ◽  
Mitochondrial Trna ◽  
Mtdna Mutations ◽  
Mitochondrial Dna Mutations ◽  
Dna Mutations ◽  
Artery Disease

Cardiovascular diseases (CVD) are one of the leading causes of morbidity and mortality worldwide. mtDNA (mitochondrial DNA) mutations are known to participate in the development and progression of some CVD. Moreover, specific types of mitochondria-mediated CVD have been discovered, such as MIEH (maternally inherited essential hypertension) and maternally inherited CHD (coronary heart disease). Maternally inherited mitochondrial CVD is caused by certain mutations in the mtDNA, which encode structural mitochondrial proteins and mitochondrial tRNA. In this review, we focus on recently identified mtDNA mutations associated with CVD (coronary artery disease and hypertension). Additionally, new data suggest the role of mtDNA mutations in Brugada syndrome and ischemic stroke, which before were considered only as a result of mutations in nuclear genes. Moreover, we discuss the molecular mechanisms of mtDNA involvement in the development of the disease.

scholarly journals Mitochondrial DNA polymorphism and cardiovascular continuum diseases

2018 ◽  
pp. 9-13
Author(s):  
М.В. Голубенко ◽  
Р.Р. Салахов ◽  
Т.В. Шумакова ◽  
С.В. Буйкин ◽  
О.А. Макеева ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Cardiovascular Diseases ◽  
Mitochondrial Genome ◽  
Dna Polymorphism ◽  
Nuclear Genome ◽  
Published Data ◽  
Human Populations ◽  
Mitochondrial Dna Polymorphism ◽  
Polymorphism Level ◽  
Cardiovascular Continuum

Митохондриальный геном кодирует жизненно важные белки субъединиц дыхательной цепи и характеризуется высоким уровнем полиморфизма в популяциях человека. Однако работы по поиску генов предрасположенности к многофакторным заболеваниям, в том числе сердечно-сосудистым, часто ограничиваются анализом ядерного генома. В то же время показано, что отдельные генотипы мтДНК могут отличаться более высокой или низкой эффективностью окислительного фосфорилирования. Выявлены ассоциации популяционного полиморфизма мтДНК с сердечно-сосудистыми заболеваниями. Согласно результатам наших исследований, а также опубликованных другими авторами результатам ассоциативных и функциональных исследований, можно говорить о том, что эффект полиморфизма мтДНК проявляется чаще не в предрасположенности к сердечно-сосудистым заболеваниям в целом, а в риске развития осложнений и коморбидных фенотипов в пределах синтропии сердечно-сосудистого континуума. Mitochondrial genome, encoding respiratory chain subunits, is characterized by high polymorphism level in human populations. In most studies for susceptibility genes for common diseases, including cardiovascular diseases, the analysis is limited to the nuclear genome. It was shown that particular mtDNA genotypes may differ by oxidative phosphorylation efficiency. Some associations of mtDNA polymorphisms with cardiovascular diseases have been found. According to our results and published data, we suggest that mtDNA effect on cardiovascular system does not manifest in predisposition to cardiovascular diseases themselves but rather in risk of complications and comorbidities in the cardiovascular continuum.

Mitochondrial cardiovascular diseases

2020 ◽  
pp. 325-342
Author(s):  
Perry Elliott ◽  
Pier D. Lambiase ◽  
Dhavendra Kumar
Keyword(s):  
Mitochondrial Dna ◽  
Hypertrophic Cardiomyopathy ◽  
Cardiovascular Diseases ◽  
Mitochondrial Genome ◽  
Mitochondrial Disease ◽  
Clinical Management ◽  
Cardiac Involvement ◽  
Mitochondrial Disorders ◽  
Barth Syndrome

This chapter begins by defining the mitochondrial genome, and the subsequent assessment of suspected mitochondrial DNA (mtDNA) disorders. The incidence and prevalence of cardiac involvement in mitochondrial disorders is covered, including the probably under-reporting of this. Different cardiovascular phenotypes associated with mitochondrial disease (arrhythmias, hypertrophic cardiomyopathy, Barth syndrome etc.) are all described, and then the clinical management of the diseases are explained. As there is no fixed treatment, pharmacological regimens to avoid, and other approaches are also included.

Oxidative Stress, Mitochondrial DNA Mutation, and Impairment of Antioxidant Enzymes in Aging

2002 ◽  
Vol 227 (9) ◽  
pp. 671-682 ◽  
Author(s):  
Yau-Huei Wei ◽  
Hsin-Chen Lee
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Antioxidant Enzymes ◽  
Oxidative Damage ◽  
Large Scale ◽  
Wide Spectrum ◽  
Radical Scavenging ◽  
Mtdna Mutations ◽  
Enhanced Production ◽  
Age Related

Mitochondria do not only produce less ATP, but they also increase the production of reactive oxygen species (ROS) as byproducts of aerobic metabolism in the aging tissues of the human and animals. It is now generally accepted that aging-associated respiratory function decline can result in enhanced production of ROS in mitochondria. Moreover, the activities of free radical-scavenging enzymes are altered in the aging process. The concurrent age-related changes of these two systems result in the elevation of oxidative stress in aging tissues. Within a certain concentration range, ROS may induce stress response of the cells by altering expression of respiratory genes to uphold the energy metabolism to rescue the cell. However, beyond the threshold, ROS may cause a wide spectrum of oxidative damage to various cellular components to result in cell death or elicit apoptosis by induction of mitochondrial membrane permeability transition and release of apoptogenic factors such as cytochrome c. Moreover, oxidative damage and large-scale deletion and duplication of mitochondrial DNA (mtDNA) have been found to increase with age in various tissues of the human. Mitochondria act like a biosensor of oxidative stress and they enable cell to undergo changes in aging and age-related diseases. On the other hand, it has recently been demonstrated that impairment in mitochondrial respiration and oxidative phosphorylation elicits an increase in oxidative stress and causes a host of mtDNA rearrangements and deletions. Here, we review work done in the past few years to support our view that oxidative stress and oxidative damage are a result of concurrent accumulation of mtDNA mutations and defective antioxidant enzymes in human aging.

MtDNA Sequence of MDS Patients Treated with CoQ10.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4912-4912
Author(s):  
Eric V. Sechman ◽  
Naomi Galili ◽  
Eric Einstein ◽  
Batool Raza ◽  
Kimberly Ferrante ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Genome ◽  
Genomic Dna ◽  
Life Quality ◽  
Small Subset ◽  
Intermediate Risk ◽  
Genome Database ◽  
Mtdna Mutations ◽  
Mtdna Sequence ◽  
Pcr Products

Abstract We conducted a pilot study to test the efficacy of coQ10 in improving the cytopenias of MDS patients with low to intermediate risk MDS. Almost every patient experienced a reduction in fatigue and improvement in life quality. Among 25 evaluable patients, 7 responded according to the International Working Group (IWG) criteria. Responses included two trilineage and 1 monolineage response, two cytogenetic responses, and two patients showed a change in FAB type from CMMoL to RA and RARS. CoQ10 is an important coenzyme that has been shown to be involved in protection against oxidative stress, inhibition of apoptosis, and generation of ATP. Mutations in mitochondrial DNA have previously been found in MDS patients. We hypothesized that acquired mutations in the mitochondrial genome may relate to the efficacy of coQ10 treatment. We therefore sequenced the mitochondrial genome (mtDNA) of 9 patients, including 4 responders and 5 nonresponders, and 2 normal samples to determine if differences in the frequency or location of mtDNA mutations could be correlated to response. Whole genomic DNA was isolated from bone marrow monocytes and the mtDNA was PCR amplified in 40 overlapping segments. The PCR products were then sequenced and compared to a mitochondrial genome database (www.mitomap.org) to identify mutations. This technique will not detect mutations present in only a small subset of DNA copies. However, mutations present in a majority of mtDNA that may directly contribute to the expansion of the MDS clone will be identified. Interestingly, although mutations were observed, no differences were found that distinguished responders from nonresponders. We conclude from this analysis that the clinical benefit to MDS patients is not related to specific mutations in the mitochondrial genome. Clinical response may instead be related to other pleiotropic effects of coQ10, such as inhibition of apoptosis.

scholarly journals How AMPK and PKA Interplay to Regulate Mitochondrial Function and Survival in Models of Ischemia and Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jingdian Zhang ◽  
Yumeng Wang ◽  
Xiaofeng Liu ◽  
Ruben K. Dagda ◽  
Ying Zhang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Protein Kinase ◽  
Cell Survival ◽  
Mitochondrial Function ◽  
Molecular Mechanisms ◽  
Temporal Dynamics ◽  
Protein Translation ◽  
Conservation Of Energy

Adenosine monophosphate-activated protein kinase (AMPK) is a conserved, redox-activated master regulator of cell metabolism. In the presence of oxidative stress, AMPK promotes cytoprotection by enhancing the conservation of energy by suppressing protein translation and by stimulating autophagy. AMPK interplays with protein kinase A (PKA) to regulate oxidative stress, mitochondrial function, and cell survival. AMPK and dual-specificity A-kinase anchoring protein 1 (D-AKAP1), a mitochondrial-directed scaffold of PKA, interact to regulate mitochondrial function and oxidative stress in cardiac and endothelial cells. Ischemia and diabetes, a chronic disease that increases the onset of cardiovascular diseases, suppress the cardioprotective effects of AMPK and PKA. Here, we review the molecular mechanisms by which AMPK and D-AKAP1/PKA interplay to regulate mitochondrial function, oxidative stress, and signaling pathways that prime endothelial cells, cardiac cells, and neurons for cytoprotection against oxidative stress. We discuss recent literature showing how temporal dynamics and localization of activated AMPK and PKA holoenzymes play a crucial role in governing cellular bioenergetics and cell survival in models of ischemia, cardiovascular diseases, and diabetes. Finally, we propose therapeutic strategies that tout localized PKA and AMPK signaling to reverse mitochondrial dysfunction, oxidative stress, and death of neurons and cardiac and endothelial cells during ischemia and diabetes.

scholarly journals Power of Proteomics in Linking Oxidative Stress and Female Infertility

2014 ◽  
Vol 2014 ◽  
pp. 1-26 ◽  
Author(s):  
Sajal Gupta ◽  
Jana Ghulmiyyah ◽  
Rakesh Sharma ◽  
Jacques Halabi ◽  
Ashok Agarwal
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Unexplained Infertility ◽  
Female Infertility ◽  
Related Disease ◽  
Large Numbers ◽  
The One ◽  
Related Proteins ◽  
Potential Biomarkers

Endometriosis, PCOS, and unexplained infertility are currently the most common diseases rendering large numbers of women infertile worldwide. Oxidative stress, due to its deleterious effects on proteins and nucleic acids, is postulated to be the one of the important mechanistic pathways in differential expression of proteins and in these diseases. The emerging field of proteomics has allowed identification of proteins involved in cell cycle, as antioxidants, extracellular matrix (ECM), cytoskeleton, and their linkage to oxidative stress in female infertility related diseases. The aim of this paper is to assess the association of oxidative stress and protein expression in the reproductive microenvironments such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as reproductive tissues and serum. The review also highlights the literature that proposes the use of the fertility related proteins as potential biomarkers for noninvasive and early diagnosis of the aforementioned diseases rather than utilizing the more invasive methods used currently. The review will highlight the power of proteomic profiles identified in infertility related disease conditions and their linkage with underlying oxidative stress. The power of proteomics will be reviewed with regard to eliciting molecular mechanisms for early detection and management of these infertility related conditions.

scholarly journals The Role of Oxidative Stress in Cardiovascular Aging and Cardiovascular Diseases

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 60
Author(s):  
Carmine Izzo ◽  
Paolo Vitillo ◽  
Paola Di Pietro ◽  
Valeria Visco ◽  
Andrea Strianese ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Stress Theory ◽  
Age Related ◽  
Theory Of Aging ◽  
Cardiovascular Aging ◽  
Primary Risk Factor ◽  
Structure And Functions

Aging can be seen as process characterized by accumulation of oxidative stress induced damage. Oxidative stress derives from different endogenous and exogenous processes, all of which ultimately lead to progressive loss in tissue and organ structure and functions. The oxidative stress theory of aging expresses itself in age-related diseases. Aging is in fact a primary risk factor for many diseases and in particular for cardiovascular diseases and its derived morbidity and mortality. Here we highlight the role of oxidative stress in age-related cardiovascular aging and diseases. We take into consideration the molecular mechanisms, the structural and functional alterations, and the diseases accompanied to the cardiovascular aging process.

scholarly journals Telomerase Does Not Improve DNA Repair in Mitochondria upon Stress but Increases MnSOD Protein under Serum-Free Conditions

2019 ◽  
Vol 21 (1) ◽  
pp. 27 ◽  
Author(s):  
Alexander Martens ◽  
Bianca Schmid ◽  
Olasubomi Akintola ◽  
Gabriele Saretzki
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Mitochondrial Dna ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
Human Fibroblasts ◽  
Cellular Systems ◽  
Human Telomerase Reverse Transcriptase ◽  
Serum Free ◽  
Mtdna Damage

Telomerase is best known for its function in maintaining telomeres but has also multiple additional, non-canonical functions. One of these functions is the decrease of oxidative stress and DNA damage due to localisation of the telomerase protein TERT into mitochondria under oxidative stress. However, the exact molecular mechanisms behind these protective effects are still not well understood. We had shown previously that overexpression of human telomerase reverse transcriptase (hTERT) in human fibroblasts results in a decrease of mitochondrial DNA (mtDNA) damage after oxidative stress. MtDNA damage caused by oxidative stress is removed via the base excision repair (BER) pathway. Therefore we aimed to analyse whether telomerase is able to improve this pathway. We applied different types of DNA damaging agents such as irradiation, arsenite treatment (NaAsO2) and treatment with hydrogen peroxide (H2O2). Using a PCR-based assay to evaluate mtDNA damage, we demonstrate that overexpression of hTERT in MRC-5 fibroblasts protects mtDNA from H2O2 and NaAsO2 induced damage, compared with their isogenic telomerase-negative counterparts. However, overexpression of hTERT did not seem to increase repair of mtDNA after oxidative stress, but promoted increased levels of manganese superoxide dismutase (MnSOD) and forkhead-box-protein O3 (FoxO3a) proteins during incubation in serum free medium as well as under oxidative stress, while no differences were found in protein levels of catalase. Together, our results suggest that rather than interfering with mitochondrial DNA repair mechanisms, such as BER, telomerase seems to increase antioxidant defence mechanisms to prevent mtDNA damage and to increase cellular resistance to oxidative stress. However, the result has to be reproduced in additional cellular systems in order to generalise our findings.

Mitochondrial DNA Mutation, Diseases, and Nutrient-Regulated Mitophagy

2019 ◽  
Vol 39 (1) ◽  
pp. 201-226 ◽  
Author(s):  
Xuan Yang ◽  
Ruoyu Zhang ◽  
Kiichi Nakahira ◽  
Zhenglong Gu
Keyword(s):  
Mitochondrial Dna ◽  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Wide Spectrum ◽  
Human Diseases ◽  
Nutrient Deficiencies ◽  
Mtdna Mutation ◽  
Mitochondrial Dna Mutation ◽  
Mtdna Mutations ◽  
Mitochondrial Homeostasis

A wide spectrum of human diseases, including cancer, neurodegenerative diseases, and metabolic disorders, have been shown to be associated with mitochondrial dysfunction through multiple molecular mechanisms. Mitochondria are particularly susceptible to nutrient deficiencies, and nutritional intervention is an essential way to maintain mitochondrial homeostasis. Recent advances in genetic manipulation and next-generation sequencing reveal the crucial roles of mitochondrial DNA (mtDNA) in various pathophysiological conditions. Mitophagy, a term coined to describe autophagy that targets dysfunctional mitochondria, has emerged as an important cellular process to maintain mitochondrial homeostasis and has been shown to be regulated by various nutrients and nutritional stresses. Given the high prevalence of mtDNA mutations in humans and their impact on mitochondrial function, it is important to investigate the mechanisms that regulate mtDNA mutation. Here, we discuss mitochondrial genetics and mtDNA mutations and their implications for human diseases. We also examine the role of mitophagy as a therapeutic target, highlighting how nutrients may eliminate mtDNA mutations through mitophagy.

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