Inherited mitochondrial genomic instability and chemical exposures

There are several types of mitochondrial cytopathies, which cause a set of disorders, arise as a result of mitochondria’s failure. Mitochondria’s functional disruption leads to development of physical, growing and cognitive disabilities and includes multiple organ pathologies, essentially disturbing the nervous and muscular systems. The origins of mitochondrial cytopathies are mutations in genes of nuclear DNA encoding mitochondrial proteins or in mitochondrial DNA. Nowadays, numerous mtDNA mutations significant to the appearance and progress of pathologies in humans are detected. In this mini-review, we accent on the mitochondrial cytopathies related to mutations of mtDNA. As well known, there are definite set of symptoms of mitochondrial cytopathies distinguishing or similar for different syndromes. The present article contains data about mutations linked with cytopathies that facilitate diagnosis of different syndromes by using genetic analysis methods. In addition, for every individual, more effective therapeutic approach could be developed after wide-range mutant background analysis of mitochondrial genome.

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“…Moreover, targeted treatment of mitochondrial diseases can be achieved via nanotube transmission of mtDNA from one cell to another. 112 , 113 …”

Section: Mtdna Mutations and Therapy Of Cytopathiesmentioning

confidence: 99%

Mitochondrial diseases caused by mtDNA mutations: a mini-review

Рыжкова

Sazonova

Sinyov

et al. 2018

TCRM

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“…Several chemicals can cause mutations in mTDNA (Valente et al, 2016). In turn, these mutations increase the sensitivity of mT to stress (Chan, 2017;Luz et al, 2017). Stress can change the morphology and function of mT through fusion and fission (Meyer et al, 2017).…”

Section: O N L I N E C O P Ymentioning

confidence: 99%

Mechanistic paradigms of cell death - revisited

Rana¹

2021

JEB

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Present review is the description of a journey that originates from Virchows' cell theory and terminates with the role of molecular switches in cell death recently proposed by Orrenius. Landmark discoveries made, in between, to characterize regulated as well as accidental cell death have also been documented. It embraces the studies that were made in early nineties to understand cellular homeostasis in health and disease. Furthermore, the effects of foreign chemicals on different cell types witnessed in late nineties have been classified into necrosis, apoptosis, autophagy etc. Since it is important to know how a cell dies, studies made in our own and other laboratories on the role of reactive oxygen species, oxidative stress, intracellular Ca2+ homeostasis, redox imbalance, mitochondrial and ER stress in cell death have also been reviewed. Possibility of a cross talk amongst these mechanisms has also been examined. It discusses the impact of wonder molecules like CYP450, GSH, metallothionein and melatonin together with enzymatic and non-enzymatic antioxidants on cell death. Understanding the cellular targets and molecular mechanisms activated by a variety of environmental xenobiotics is fundamental for human health risk assessment. It is expected that the contents of this article will answer the fundamental question- why and how cells die.

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“…This may be why it has been challenging to detect mitochondrial DNA (mtDNA) mutagenesis in laboratory models after chemical exposure ( Valente et al , 2016 ), despite reasons to expect such mutagenesis ( Meyer and Chan, 2017 ). Genetic deficiencies in these processes, however, may complicate these responses; for example, there are a large number of mutations affecting the mtDNA replication machinery, and these can result in sensitivity to stressors ( Chan, 2017 ). Mitochondrial fusion and fission are increasingly understood to be a key part of the mitochondrial stress response: mitochondrial morphology changes in a nonmonotonic fashion in response to mitochondrial stress ( Meyer et al , 2017 ), and there is evidence that the genetic loss of such processes (which occurs in the human population) greatly increases sensitivity to some chemicals ( Luz et al , 2017 ).…”

Section: Cutting-edge Areas Of Researchmentioning

confidence: 99%

Mitochondrial Toxicity

Meyer

Hartman

Mello

2018

Toxicological Sciences

135

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Recent decades have seen a rapid increase in reported toxic effects of drugs and pollutants on mitochondria. Researchers have also documented many genetic differences leading to mitochondrial diseases, currently reported to affect ∼1 person in 4,300, creating a large number of potential gene-environment interactions in mitochondrial toxicity. We briefly review this history, and then highlight cutting-edge areas of mitochondrial research including the role of mitochondrial reactive oxygen species in signaling; increased understanding of fundamental biological processes involved in mitochondrial homeostasis (DNA maintenance and mutagenesis, mitochondrial stress response pathways, fusion and fission, autophagy and biogenesis, and exocytosis); systemic effects resulting from mitochondrial stresses in specific cell types; mitochondrial involvement in immune function; the growing evidence of long-term effects of mitochondrial toxicity; mitochondrial-epigenetic cross-talk; and newer approaches to test chemicals for mitochondrial toxicity. We also discuss the potential importance of hormetic effects of mitochondrial stressors. Finally, we comment on future areas of research we consider critical for mitochondrial toxicology, including increased integration of clinical, experimental laboratory, and epidemiological (human and wildlife) studies; improved understanding of biomarkers in the human population; and incorporation of other factors that affect mitochondria, such as diet, exercise, age, and nonchemical stressors.

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Inherited mitochondrial genomic instability and chemical exposures

Cited by 29 publications

References 167 publications

Mitochondrial diseases caused by mtDNA mutations: a mini-review

Mitochondrial diseases caused by mtDNA mutations: a mini-review

Mechanistic paradigms of cell death - revisited

Mitochondrial Toxicity

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