Risk of mitochondrial deletions is affected by the global secondary structure of the human mitochondrial genome

Mikhailova, Alina A.; Shamanskiy, Viktor N.; Ushakova, Kristina; Oreshkov, Sergei; Knorre, Dmitry A.; Tretiakov, Evgenii; Zazhytska, Marianna; Lukowski, Samuel W.; Liou, Chia‐Wei; Lin, Tsu-Kung; Kunz, Wolfram S.; Reymond, Alexandre; Мазунин, И. О.; Bazykin, Georgii A.; Gunbin, Konstantin; Fellay, Jacques; Tanaka, Masashi; Khrapko, Konstantin; Popadin, Konstantin

doi:10.1101/603282

Cited by 3 publications

(3 citation statements)

References 105 publications

(319 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both oocyte and ovarian cell mitochondria are important for the correct folliculogenesis and oocyte maturation [ 13 , 14 , 15 , 16 ]. As to the risk of mitochondrial DNA deletions, it was shown to be affected by the global secondary structure of the mitochondrial genome [ 17 ].…”

Section: Molecular Mechanismsmentioning

confidence: 99%

“…Moreover, aging-related mitochondrial (mt) DNA instability also leads to an accumulation of mtDNA mutations in the oocyte, leading to the deterioration of oocyte quality in terms of competence and the risk of transmitting mitochondrial abnormalities to offspring [ 14 ]. As mentioned above, the risk of mtDNA damage is also conditioned by epigenetic factors, especially the global secondary structure of the mitochondrial genome; certain patterns of the global secondary structure of the human single-stranded heavy chain of mtDNA make the DNA molecule more prone to deletions than others [ 17 ].…”

Section: Molecular Mechanismsmentioning

confidence: 99%

See 1 more Smart Citation

Ovarian Aging: Molecular Mechanisms and Medical Management

Galán-Lázaro¹,

Mendoza-Tesarik²

2021

IJMS

View full text Add to dashboard Cite

This is a short review of the basic molecular mechanisms of ovarian aging, written with a particular focus on the use of this data to improve the diagnostic and therapeutic protocols both for women affected by physiological (age-related) ovarian decay and for those suffering premature ovarian insufficiency. Ovarian aging has a genetic basis that conditions the ovarian activity via a plethora of cell-signaling pathways that control the functions of different types of cells in the ovary. There are various factors that can influence these pathways so as to reduce their efficiency. Oxidative stress, often related to mitochondrial dysfunction, leading to the apoptosis of ovarian cells, can be at the origin of vicious circles in which the primary cause feeds back other abnormalities, resulting in an overall decline in the ovarian activity and in the quantity and quality of oocytes. The correct diagnosis of the molecular mechanisms involved in ovarian aging can serve to design treatment strategies that can slow down ovarian decay and increase the quantity and quality of oocytes that can be obtained for an in vitro fertilization attempt. The available treatment options include the use of antioxidants, melatonin, growth hormones, and mitochondrial therapies. All of these treatments have to be considered in the context of each couple’s history and current clinical condition, and a customized (patient-tailored) treatment protocol is to be elaborated.

show abstract

Section: Molecular Mechanismsmentioning

confidence: 99%

Section: Molecular Mechanismsmentioning

confidence: 99%

Ovarian Aging: Molecular Mechanisms and Medical Management

Galán-Lázaro¹,

Mendoza-Tesarik²

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Paradoxically, while DRs are the motif most consistently associated with mtDNA deletion breakpoints (BPs), despite preliminary reports (Khaidakov et al 2006, Lakshmanan et al 2012, Yang et al 2013, no correlation with species MLS was seen in recent studies (Lakshmanan et al 2015). In contrast, with the exception of one preprint (Mikhailova et al 2020), IRs are not known to be associated with mtDNA deletions (Dong et al 2014), although they do show a negative relationship with species MLS (Yang et al 2013) and may contribute to inversions (Tremblay-Belzile et al 2015). Whether age-related mtDNA inversions underlie any pathology, however, requires further study.…”

Section: Introductionmentioning

confidence: 96%

Triplex and other DNA motifs show motif-specific associations with mitochondrial DNA deletions and species lifespan

Pabis¹

2020

Preprint

View full text Add to dashboard Cite

The “theory of resistant biomolecules” posits that long-lived species show resistance to molecular damage at the level of their biomolecules. Here, we test this hypothesis in the context of mitochondrial DNA (mtDNA) as it implies that predicted mutagenic DNA motifs should be inversely correlated with species maximum lifespan (MLS).First, we confirmed that guanine-quadruplex (GQ) and direct repeat (DR) motifs are mutagenic, as they associate with mtDNA deletions in the human major arc of mtDNA, while also adding mirror repeat (MR) and intramolecular triplex motifs to a growing list of potentially mutagenic features. What is more, triplex motifs showed disease-specific associations with deletions and an apparent interaction with GQ motifs.Surprisingly, even though DR, MR and GQ motifs were associated with mtDNA deletions, their correlation with MLS was explained by the biased base composition of mtDNA. Only triplex motifs negatively correlated with MLS and these results remained stable even after adjusting for body mass, phylogeny, mtDNA base composition and effective number of codons.Taken together, our work highlights the importance of base composition for the comparative biogerontology of mtDNA and suggests that future research on mitochondrial triplex motifs is warranted.

show abstract

MtDNA deletions and aging

Sprason,

Tucker,

Clancy

2024

Front. Aging

View full text Add to dashboard Cite

Aging is the major risk factor in most of the leading causes of mortality worldwide, yet its fundamental causes mostly remain unclear. One of the clear hallmarks of aging is mitochondrial dysfunction. Mitochondria are best known for their roles in cellular energy generation, but they are also critical biosynthetic and signaling organelles. They also undergo multiple changes with organismal age, including increased genetic errors in their independent, circular genome. A key group of studies looking at mice with increased mtDNA mutations showed that premature aging phenotypes correlated with increased deletions but not point mutations. This generated an interest in mitochondrial deletions as a potential fundamental cause of aging. However, subsequent studies in different models have yielded diverse results. This review summarizes the research on mitochondrial deletions in various organisms to understand their possible roles in causing aging while identifying the key complications in quantifying deletions across all models.

show abstract

Risk of mitochondrial deletions is affected by the global secondary structure of the human mitochondrial genome

Cited by 3 publications

References 105 publications

Ovarian Aging: Molecular Mechanisms and Medical Management

Ovarian Aging: Molecular Mechanisms and Medical Management

Triplex and other DNA motifs show motif-specific associations with mitochondrial DNA deletions and species lifespan

MtDNA deletions and aging

Contact Info

Product

Resources

About