Somatic mitochondrial DNA mutations in different grades of glioma

2021 ◽  
Author(s):  
Bee Hong Soon ◽  
Nadiah Abu ◽  
Nor Azian Abdul Murad ◽  
Sue-Mian Then ◽  
Azizi Abu Bakar ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Brain Cancer ◽  
Clinical Phenotype ◽  
Mitochondrial Respiratory Chain ◽  
Future Research ◽  
Glioma Tissue ◽  
Tissue Samples ◽  
Mtdna Mutations ◽  
Dna Mutations ◽  
The Relationship

Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.

Do mitochondrial DNA mutations play the key role in chronification of sterile inflammation? Special focus on atherosclerosis

2020 ◽  
Vol 26 ◽  
Author(s):  
Alexander N. Orekhov ◽  
Elena V. Gerasimova ◽  
Vasily N. Sukhorukov ◽  
Anastasia V. Poznyak ◽  
Nikita G. Nikiforov
Keyword(s):  
Innate Immunity ◽  
Mitochondrial Dna ◽  
Low Density Lipoprotein ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Sterile Inflammation ◽  
Special Focus ◽  
Mitochondrial Dysfunctions ◽  
Mtdna Mutations ◽  
Dna Mutations

Background: The elucidation of mechanisms implicated in the chronification of inflammation is able to shed the light on the pathogenesis of disorders that are responsible for the majority of the incidence of disease and deaths, and also causes of ageing. Atherosclerosis is an example of the most significant inflammatory pathology. The inflammatory response of innate immunity is implicated in the development of atherosclerosis arising locally or focally. Modified low-density lipoprotein (LDL) was regarded as the trigger for this response. No atherosclerotic changes in the arterial wall occur due to the quick decrease in inflammation rate. Nonetheless, the atherosclerotic lesion formation can be a result of the chronification of local inflammation, which, in turn, is caused by alteration of the response of innate immunity. Objective: In this review, we discussed potential mechanisms of the altered response of the immunity in atherosclerosis with a particular emphasis on mitochondrial dysfunctions. Conclusion: A few mitochondrial dysfunctions can be caused by the mitochondrial DNA (mtDNA) mutations. Moreover, mtDNA mutations were found to affect the development of defective mitophagy. Modern investigations have demonstrated the controlling mitophagy function in the response of the immune system. Therefore, we hypothesized that impaired mitophagy, as a consequence of mutations in mtDNA, can raise a disturbed innate immunity response resulting in the chronification of inflammation in atherosclerosis.

scholarly journals Mitochondrial DNA 4977 bp Deletion in Chronic Cervicitis and Cervix Cancers

2012 ◽  
Vol 15 (1) ◽  
pp. 25-29 ◽  
Author(s):  
M Kara ◽  
A Tatar ◽  
B Borekci ◽  
F Dagli ◽  
S Oztas
Keyword(s):  
Mitochondrial Dna ◽  
Inflammatory Diseases ◽  
Turkish Population ◽  
Cervix Cancer ◽  
Control Group ◽  
Mtdna Mutations ◽  
Long Time ◽  
And Control ◽  
The Relationship ◽  
Chronic Cervicitis

Mitochondrial DNA 4977 bp Deletion in Chronic Cervicitis and Cervix CancersMitochondrial DNA (mtDNA) mutations have been implied in many diseases including cancer and inflammatory diseases. The aim of this study is to investigate the relationship between the 4977 bp deletion of the mtDNA and chronic cervicitis or cervix cancer in patients. The study included a group of patients with chronic cervicitis or cervix cancer, and a control group consisting of individuals without any cervical tissue disease. A total of 72 subjects in an East Turkish population were included in the study. Of these, 35 had chronic cervicitis, 21 had cervix cancer and 16 served as the control group. Isolation of mtDNA was performed from the tissues of these patients and then mtDNA deletions were studied using polymerase chain reaction (PCR). In the cancer groups, there were 9.5% heteroplasmic and homoplasmic deletions. There were no homoplasmic deletions in the cervicitis and control groups, but the frequencies of heteroplasmic deletions were 80.0 and 31.2%, respectively. Chronic inflammation leading to increased reactive oxygen species (ROS) may be the cause of the high mtDNA 4977 bp deletion frequencies in cancer and cervicitis. The older age of the cancer patient may suggest that ageing in addition to long time exposure to ROS may lead to deletions and subsequently cancer. This is the first study to investigate the relationship of the mtDNA 4977 bp deletion to chronic cervicitis and cervix cancer.

scholarly journals Mitochondrial DNA alterations underlie an irreversible shift to aerobic glycolysis in fumarate hydratase–deficient renal cancer

2021 ◽  
Vol 14 (664) ◽  
pp. eabc4436
Author(s):  
Daniel R. Crooks ◽  
Nunziata Maio ◽  
Martin Lang ◽  
Christopher J. Ricketts ◽  
Cathy D. Vocke ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Respiratory Chain ◽  
Human Cancer ◽  
Aerobic Glycolysis ◽  
Krebs Cycle ◽  
Fumarate Hydratase ◽  
Mitochondrial Respiratory Chain ◽  
Respiratory Chain Complexes ◽  
Cycle Enzyme ◽  
Mtdna Mutations

Understanding the mechanisms of the Warburg shift to aerobic glycolysis is critical to defining the metabolic basis of cancer. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an aggressive cancer characterized by biallelic inactivation of the gene encoding the Krebs cycle enzyme fumarate hydratase, an early shift to aerobic glycolysis, and rapid metastasis. We observed impairment of the mitochondrial respiratory chain in tumors from patients with HLRCC. Biochemical and transcriptomic analyses revealed that respiratory chain dysfunction in the tumors was due to loss of expression of mitochondrial DNA (mtDNA)–encoded subunits of respiratory chain complexes, caused by a marked decrease in mtDNA content and increased mtDNA mutations. We demonstrated that accumulation of fumarate in HLRCC tumors inactivated the core factors responsible for replication and proofreading of mtDNA, leading to loss of respiratory chain components, thereby promoting the shift to aerobic glycolysis and disease progression in this prototypic model of glucose-dependent human cancer.

scholarly journals Do Somatic Mitochondrial DNA Mutations Contribute to Parkinson's Disease?

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Joanne Clark ◽  
Ying Dai ◽  
David K. Simon
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Point Mutations ◽  
Premature Aging ◽  
Mtdna Mutations ◽  
Dna Mutations ◽  
Mitochondrial Dna Polymerase ◽  
Mitochondrial Defect

A great deal of evidence supports a role for mitochondrial dysfunction in the pathogenesis of Parkinson's disease (PD), although the origin of the mitochondrial dysfunction in PD remains unclear. Expression of mitochondrial DNA (mtDNA) from PD patients in “cybrid” cell lines recapitulates the mitochondrial defect, implicating a role for mtDNA mutations, but the specific mutations responsible for the mitochondrial dysfunction in PD have been difficult to identify. Somatic mtDNA point mutations and deletions accumulate with age and reach high levels in substantia nigra (SN) neurons. Mutations in mitochondrial DNA polymeraseγ(POLG) that lead to the accumulation of mtDNA mutations are associated with a premature aging phenotype in “mutator” mice, although overt parkinsonism has not been reported in these mice, and with parkinsonism in humans. Together these data support, but do not yet prove, the hypothesis that the accumulation of somatic mtDNA mutations in SN neurons contribute to the pathogenesis of PD.

scholarly journals Clinical phenotype of mitochondrial diabetes due to rare mitochondrial DNA mutations

2020 ◽  
Vol 81 (2-3) ◽  
pp. 68-77
Author(s):  
Anne-Gaëlle Decoux-Poullot ◽  
Sylvie Bannwarth ◽  
Vincent Procaccio ◽  
Anne-Sophie Lebre ◽  
Claude Jardel ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Clinical Phenotype ◽  
Mitochondrial Dna Mutations ◽  
Dna Mutations ◽  
Mitochondrial Diabetes

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.

Neurodegenerative Diseases Associated with Mitochondrial DNA Mutations

2020 ◽  
Vol 26 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Olga A. Zhunina ◽  
Nikita G. Yabbarov ◽  
Andrey V. Grechko ◽  
Shaw-Fang Yet ◽  
Igor A. Sobenin ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Leigh Syndrome ◽  
Progressive External Ophthalmoplegia ◽  
Special Focus ◽  
Mtdna Mutations ◽  
Dna Mutations ◽  
Alzheimer’S Diseases ◽  
Alzheimer's Diseases

Mitochondrial dysfunction underlies several human chronic pathologies, including cardiovascular disorders, cancers and neurodegenerative diseases. Impaired mitochondrial function associated with oxidative stress can be a result of both nuclear and mitochondrial DNA (mtDNA) mutations. Neurological disorders associated with mtDNA mutations include mitochondrial encephalomyopathy, chronic progressive external ophthalmoplegia, neurogenic weakness, and Leigh syndrome. Moreover, mtDNA mutations were shown to play a role in the development of Parkinson and Alzheimer’s diseases. In this review, current knowledge on the distribution and possible roles of mtDNA mutations in the onset and development of various neurodegenerative diseases, with special focus on Parkinson’s and Alzheimer’s diseases has been discussed.

scholarly journals Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 160
Author(s):  
Tatiana V. Kirichenko ◽  
Anastasia I. Ryzhkova ◽  
Vasily V. Sinyov ◽  
Marina D. Sazonova ◽  
Varvara A. Orekhova ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Regression Analysis ◽  
Linear Regression Analysis ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Mtdna Mutations ◽  
Media Thickness ◽  
Dna Mutations ◽  
Novosibirsk Region ◽  
Atherosclerosis Development

The search for markers of predisposition to atherosclerosis development is very important for early identification of individuals with a high risk of cardiovascular disease. The aim of the present study was to investigate the association of mitochondrial DNA mutations with carotid intima-media thickness and to determine the impact of mitochondrial heteroplasmy measurements in the prognosis of atherosclerosis development. This cross-sectional, population-based study was conducted in 468 subjects from the Novosibirsk region. It was shown that the mean (carotid intima-media thickness) cIMT correlated with the following mtDNA mutations: m.15059G>A (r = 0.159, p = 0.001), m.12315G>A (r = 0.119; p = 0.011), m.5178C>A (r = 0.114, p = 0.014), and m.3256C>T (r = 0.130, p = 0.011); a negative correlation with mtDNA mutations m.14846G>A (r = −0.111, p = 0.042) and m.13513G>A (r = −0.133, p = 0.004) was observed. In the linear regression analysis, the addition of the set of mtDNA mutations to the conventional cardiovascular risk factors increased the ability to predict the cIMT variability from 17 to 27%. Multi-step linear regression analysis revealed the most important predictors of mean cIMT variability: age, systolic blood pressure, blood levels of total cholesterol, LDL and triglycerides, as well as the mtDNA mutations m.13513G>A, m.15059G>A, m.12315G>A, and m.3256C>T. Thus, a high predictive value of mtDNA mutations for cIMT variability was demonstrated. The association of mutation m.13513G>A and m.14846G>A with a low value of cIMT, demonstrated in several studies, represents a potential for the development of anti-atherosclerotic gene therapy.

scholarly journals Mitochondrial DNA mutations in disease and aging

2011 ◽  
Vol 193 (5) ◽  
pp. 809-818 ◽  
Author(s):  
Chan Bae Park ◽  
Nils-Göran Larsson
Keyword(s):  
Mitochondrial Dna ◽  
Oxidative Phosphorylation ◽  
Molecular Level ◽  
Mitochondrial Diseases ◽  
Mitochondrial Genetics ◽  
Replication Errors ◽  
Mtdna Mutations ◽  
Accumulated Damage ◽  
Dna Mutations ◽  
Human Pathology

The small mammalian mitochondrial DNA (mtDNA) is very gene dense and encodes factors critical for oxidative phosphorylation. Mutations of mtDNA cause a variety of human mitochondrial diseases and are also heavily implicated in age-associated disease and aging. There has been considerable progress in our understanding of the role for mtDNA mutations in human pathology during the last two decades, but important mechanisms in mitochondrial genetics remain to be explained at the molecular level. In addition, mounting evidence suggests that most mtDNA mutations may be generated by replication errors and not by accumulated damage.

Sign in / Sign up

Export Citation Format

Share Document