Pathogenic Mitochondria DNA Mutations: Current Detection Tools and Interventions

Mustafa, Mohd Fazirul; Fakurazi, Sharida; Abdullah, Maizaton Atmadini; Maniam, Sandra

doi:10.3390/genes11020192

Cited by 39 publications

(26 citation statements)

References 79 publications

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“…Additionally, Ca 2+ is the major agent in ER-mitochondrial communication, necessary for proper cellular signalling, membrane dynamics and lipid transfer, and violation of this connection may cause disease development [ 43 ]. Due to proximity to the source of ROS generation and the lack of histones and DNA repair mechanisms, mtDNA is more assailable to OS damage and has a higher chance of acquiring mutation [ 44 ]. Another marker of healthy mitochondria, associated with many developmental disorders and age-related diseases, is mtDNA copy number [ 45 ].…”

Section: Role Of Mitochondria In Pcosmentioning

confidence: 99%

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Dabravolski

Nikiforov

Eid

et al. 2021

IJMS

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Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.

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Section: Role Of Mitochondria In Pcosmentioning

confidence: 99%

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Dabravolski

Nikiforov

Eid

et al. 2021

IJMS

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“…Mitochondrial interventions and gene therapy were briefly reviewed and associated with mitochondrial diseases [208][209][210]. Meanwhile, mitochondrial biomarkers may serve as an early detection tool through the development of a commercial kit (PCMT) as previously discussed [105].…”

Section: Future Perspectives Of Mtdna Biomarkersmentioning

confidence: 99%

“…Researchers can identify the pathogenicity and therapeutic potential of a particular mtDNA mutation due to current advancements in vitro mitochondrial intervention. Previously, the patented method proposed a procedure of transferring artificial healthy mitochondria which removes damaged mtDNA without genetic manipulation [210]. A similar concept has been described by Caicedo et al Prostate and renal (i) Mitochondrial predisposition factor in North American white individuals.…”

Section: Future Perspectives Of Mtdna Biomarkersmentioning

confidence: 99%

The Uprising of Mitochondrial DNA Biomarker in Cancer

2021

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Cancer is a heterogeneous group of diseases, the progression of which demands an accumulation of genetic mutations and epigenetic alterations of the human nuclear genome or possibly in the mitochondrial genome as well. Despite modern diagnostic and therapeutic approaches to battle cancer, there are still serious concerns about the increase in death from cancer globally. Recently, a growing number of researchers have extensively focused on the burgeoning area of biomarkers development research, especially in noninvasive early cancer detection. Intergenomic cross talk has triggered researchers to expand their studies from nuclear genome-based cancer researches, shifting into the mitochondria-mediated associations with carcinogenesis. Thus, it leads to the discoveries of established and potential mitochondrial biomarkers with high specificity and sensitivity. The research field of mitochondrial DNA (mtDNA) biomarkers has the great potential to confer vast benefits for cancer therapeutics and patients in the future. This review seeks to summarize the comprehensive insights of nuclear genome cancer biomarkers and their usage in clinical practices, the intergenomic cross talk researches that linked mitochondrial dysfunction to carcinogenesis, and the current progress of mitochondrial cancer biomarker studies and development.

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“…If maternal inheritance or gender-specific symptoms are suspected, it is necessary to examine the presence of mtDNA mutations. The approaches currently used for mtDNA mutation analysis include WES, mitoexome, mtDNA sequencing and WGS [51].…”

Section: The Search For Diabetes-related Mitochondrial Mutationsmentioning

confidence: 99%

“…Mutations affecting these regions have also been reported in other human diseases, including ocular myopathy, myoclonic epilepsy and ragged red muscle fibers (MERRF) and cardiomyopathies. It is therefore interesting to compare the hot-spot of diabetes-related mtDNA mutations with hot-spots of other mitochondrial diseases [51].The effects of these mutations naturally affect mitochondrial protein synthesis resulting in overall impairment of mitochondrial function, reduced ATP production and cellular loss of function, which appears to be most prominent in cell types heavily dependent on energy production.…”

Section: Analysis Of Pathogenic Mtdna Mutations In Diabetes Patientsmentioning

confidence: 99%

The Role of Mitochondrial Mutations and Chronic Inflammation in Diabetes

Dabravolski

Orekhova

Baig

et al. 2021

IJMS

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Diabetes mellitus and related disorders significantly contribute to morbidity and mortality worldwide. Despite the advances in the current therapeutic methods, further development of anti-diabetic therapies is necessary. Mitochondrial dysfunction is known to be implicated in diabetes development. Moreover, specific types of mitochondrial diabetes have been discovered, such as MIDD (maternally inherited diabetes and deafness) and DAD (diabetes and Deafness). Hereditary mitochondrial disorders are caused by certain mutations in the mitochondrial DNA (mtDNA), which encodes for a substantial part of mitochondrial proteins and mitochondrial tRNA necessary for mitochondrial protein synthesis. Study of mtDNA mutations is challenging because the pathogenic phenotype associated with such mutations depends on the level of its heteroplasmy (proportion of mtDNA copies carrying the mutation) and can be tissue-specific. Nevertheless, modern sequencing methods have allowed describing and characterizing a number of mtDNA mutations associated with human disorders, and the list is constantly growing. In this review, we provide a list of mtDNA mutations associated with diabetes and related disorders and discuss the mechanisms of their involvement in the pathology development.

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Pathogenic Mitochondria DNA Mutations: Current Detection Tools and Interventions

Cited by 39 publications

References 79 publications

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

The Uprising of Mitochondrial DNA Biomarker in Cancer

The Role of Mitochondrial Mutations and Chronic Inflammation in Diabetes

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