Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers

Chen, Kuo; Lü, Ping; Beeraka, Narasimha M; Sukocheva, Olga; Madhunapantula, Subba Rao V.; Liu, Junqi; Sinelnikov, Mikhail Y.; Николенко, В.Н.; Bulygin, Kirill V.; Mikhaleva, L.M.; Решетов, И. В.; Gu, Yuanting; Zhang, Jin; Cao, Yu; Somasundaram, Siva G; Kirkland, Cecil E; Fan, Ruitai; Aliev, Gjumrakch

doi:10.1016/j.semcancer.2020.09.012

Cited by 138 publications

(117 citation statements)

References 253 publications

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“…Concerning epigenetic mechanisms occurring within mitochondria, few studies have demonstrated the presence of ncRNAs inside these organelles, both nuclear- and mitochondria-encoded, which seem to be mainly involved in the communication between the nucleus and the mitochondria, at both anterograde and retrograde signaling levels [reviewed in 6]. Moreover, although mtDNA organization is not supported by histones, mtDNA interacts with multiple proteins, including TFAM, mitochondrial single-stranded DNA binding protein and Twinkle mtDNA helicase to create nucleoprotein structures called nucleoids, which could be regulated by epigenetic mechanisms, such as acetylation and phosphorylation [ 33 ]. However, many more studies have focused on the role of mtDNA methylation and hydroxymethylation as mitoepigenetic mechanisms, and these epigenetic marks will be the main focus of the present review.…”

Section: Mitoepigeneticsmentioning

confidence: 99%

Mitochondrial DNA Methylation and Human Diseases

Stoccoro

Coppedè

2021

IJMS

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Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

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Section: Mitoepigeneticsmentioning

confidence: 99%

Mitochondrial DNA Methylation and Human Diseases

Stoccoro

Coppedè

2021

IJMS

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“…It is well known that mtDNA encodes for vital subunits involved in OXPHOS by which mitochondria provides energy supply and mtROS balance is maintained. Oxidative mtDNA lesion hence contributes to defects in OXPHOS, which provides insufficient demands of a cell for energy and triggers excessive ROS production, thus creating a vicious cycle [ 30 ]. Oxidative damage to mtDNA, particularly those that affect ETC components, is suspected of contributing to onset and the progression of various human mitochondrial disorders [ 31 ].…”

Section: Mitochondrial Oxidative Stress and Epilepsymentioning

confidence: 99%

Antioxidants Targeting Mitochondrial Oxidative Stress: Promising Neuroprotectants for Epilepsy

Yang

Guan

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Mitochondria are major sources of reactive oxygen species (ROS) within the cell and are especially vulnerable to oxidative stress. Oxidative damage to mitochondria results in disrupted mitochondrial function and cell death signaling, finally triggering diverse pathologies such as epilepsy, a common neurological disease characterized with aberrant electrical brain activity. Antioxidants are considered as promising neuroprotective strategies for epileptic condition via combating the deleterious effects of excessive ROS production in mitochondria. In this review, we provide a brief discussion of the role of mitochondrial oxidative stress in the pathophysiology of epilepsy and evidences that support neuroprotective roles of antioxidants targeting mitochondrial oxidative stress including mitochondria-targeted antioxidants, polyphenols, vitamins, thiols, and nuclear factor E2-related factor 2 (Nrf2) activators in epilepsy. We point out these antioxidative compounds as effectively protective approaches for improving prognosis. In addition, we specially propose that these antioxidants exert neuroprotection against epileptic impairment possibly by modulating cell death interactions, notably autophagy-apoptosis, and autophagy-ferroptosis crosstalk.

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“…Mitochondrial DNA (mtDNA) is more susceptible than nuclear DNA to mutagen-induced damage. As in other types of cancers [78,79], alterations in mtDNA in HCC have been revealed. So-called "common deletion" is the most common mitochondrial alteration.…”

Section: Mutations In Mitochondrial Dna and Related Genesmentioning

confidence: 85%

Thyroid Hürthle Cell Carcinoma: Clinical, Pathological, and Molecular Features

Kure

Ohashi

2020

Cancers

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Hürthle cell carcinoma (HCC) represents 3–4% of thyroid carcinoma cases. It is considered to be more aggressive than non-oncocytic thyroid carcinomas. However, due to its rarity, the pathological characteristics and biological behavior of HCC remain to be elucidated. The Hürthle cell is characterized cytologically as a large cell with abundant eosinophilic, granular cytoplasm, and a large hyperchromatic nucleus with a prominent nucleolus. Cytoplasmic granularity is due to the presence of numerous mitochondria. These mitochondria display packed stacking cristae and are arranged in the center. HCC is more often observed in females in their 50–60s. Preoperative diagnosis is challenging, but indicators of malignancy are male, older age, tumor size > 4 cm, a solid nodule with an irregular border, or the presence of psammoma calcifications according to ultrasound. Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas, or clinically detectable cervical nodal metastases, but total thyroidectomy is recommended for tumors larger than 4 cm. The effectiveness of radioactive iodine is still debated. Molecular changes involve cellular signaling pathways and mitochondria-related DNA. Current knowledge of Hürthle cell carcinoma, including clinical, pathological, and molecular features, with the aim of improving clinical management, is reviewed.

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Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers

Cited by 138 publications

References 253 publications

Mitochondrial DNA Methylation and Human Diseases

Mitochondrial DNA Methylation and Human Diseases

Antioxidants Targeting Mitochondrial Oxidative Stress: Promising Neuroprotectants for Epilepsy

Thyroid Hürthle Cell Carcinoma: Clinical, Pathological, and Molecular Features

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