scholarly journals Twist and Turn—Topoisomerase Functions in Mitochondrial DNA Maintenance

2019 ◽  
Vol 20 (8) ◽  
pp. 2041 ◽  
Author(s):  
Steffi Goffart ◽  
Anu Hangas ◽  
Jaakko L. O. Pohjoismäki
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Topology Control ◽  
Current Knowledge ◽  
Genome Maintenance ◽  
Frequent Use ◽  
Long Time ◽  
Topoisomerase 2 ◽  
Dna Maintenance ◽  
Insight Into

Like any genome, mitochondrial DNA (mtDNA) also requires the action of topoisomerases to resolve topological problems in its maintenance, but for a long time, little was known about mitochondrial topoisomerases. The last years have brought a closer insight into the function of these fascinating enzymes in mtDNA topology regulation, replication, transcription, and segregation. Here, we summarize the current knowledge about mitochondrial topoisomerases, paying special attention to mammalian mitochondrial genome maintenance. We also discuss the open gaps in the existing knowledge of mtDNA topology control and the potential involvement of mitochondrial topoisomerases in human pathologies. While Top1mt, the only exclusively mitochondrial topoisomerase in mammals, has been studied intensively for nearly a decade, only recent studies have shed some light onto the mitochondrial function of Top2β and Top3α, enzymes that are shared between nucleus and mitochondria. Top3α mediates the segregation of freshly replicated mtDNA molecules, and its dysfunction leads to mtDNA aggregation and copy number depletion in patients. Top2β, in contrast, regulates mitochondrial DNA replication and transcription through the alteration of mtDNA topology, a fact that should be acknowledged due to the frequent use of Topoisomerase 2 inhibitors in medical therapy.

scholarly journals Plant Organelle DNA Maintenance

Plants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 683 ◽  
Author(s):  
Niaz Ahmad ◽  
Brent L. Nielsen
Keyword(s):  
Copy Number ◽  
Developmental Stages ◽  
Higher Plants ◽  
Current Knowledge ◽  
Higher Plant ◽  
Organelle Dna ◽  
Number Variation ◽  
A Cell ◽  
Genome Copy Number ◽  
Dna Maintenance

Plant cells contain two double membrane bound organelles, plastids and mitochondria, that contain their own genomes. There is a very large variation in the sizes of mitochondrial genomes in higher plants, while the plastid genome remains relatively uniform across different species. One of the curious features of the organelle DNA is that it exists in a high copy number per mitochondria or chloroplast, which varies greatly in different tissues during plant development. The variations in copy number, morphology and genomic content reflect the diversity in organelle functions. The link between the metabolic needs of a cell and the capacity of mitochondria and chloroplasts to fulfill this demand is thought to act as a selective force on the number of organelles and genome copies per organelle. However, it is not yet clear how the activities of mitochondria and chloroplasts are coordinated in response to cellular and environmental cues. The relationship between genome copy number variation and the mechanism(s) by which the genomes are maintained through different developmental stages are yet to be fully understood. This Special Issue has several contributions that address current knowledge of higher plant organelle DNA. Here we briefly introduce these articles that discuss the importance of different aspects of the organelle genome in higher plants.

scholarly journals Molecules Produced by Probiotics and Intestinal Microorganisms with Immunomodulatory Activity

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 391 ◽  
Author(s):  
Susana Delgado ◽  
Borja Sánchez ◽  
Abelardo Margolles ◽  
Patricia Ruas-Madiedo ◽  
Lorena Ruiz
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Scientific Evidence ◽  
Health Benefit ◽  
Intestinal Bacteria ◽  
Molecular Techniques ◽  
Immunomodulatory Activity ◽  
Long Time ◽  
Health Promoting ◽  
Insight Into

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The probiotic microorganisms most commonly used in the food and pharmacy industry belong to Lactobacillus and Bifidobacterium, and several strains of these genera have demonstrated beneficial attributes. In addition, some other intestinal bacteria inhabiting the human microbiota, such as Faecalibacterium prausnitzii and Akkermansia muciniphila, have recently been discovered and are able to display health-promoting effects in animal and human trials. The beneficial properties of probiotics have been known for a long time, although little is known about the molecular mechanisms and the molecules responsible for their effects. However, in recent years, advances in microbiome studies, and the use of novel analytical and molecular techniques have allowed a deeper insight into their effects at the molecular level. This review summarizes the current knowledge of some of the molecules of probiotics and other intestinal commensal bacteria responsible for their immunomodulatory effect, focusing on those with more solid scientific evidence.

scholarly journals Gastric Microbiota: Tracing the Culprit

2017 ◽  
Vol 90 (4) ◽  
pp. 369-376 ◽  
Author(s):  
Cristian Vasile Petra ◽  
Aronel Rus ◽  
Dan Lucian Dumitrașcu
Keyword(s):  
Current Knowledge ◽  
Scientific Evidence ◽  
Diagnostic Methods ◽  
Culture Independent ◽  
Long Time ◽  
Health And Disease ◽  
H Pylori ◽  
Insight Into ◽  
Gastric Microbiota ◽  
Entire Gastrointestinal Tract

The gastric environment has been long time considered bacteria-free, but the discovery of Helicobacter pylori (H. pylori) in 1982 superseded this conception. Over the last decades new diagnostic methods have been developed, starting with culture-dependent and advancing to culture-independent ones. These modern techniques provide new insight into the composition and influence of this ecosystem on the entire gastrointestinal tract. H. pylori is no longer considered the only microorganism in the stomach, other non-H. pylori microbial species may populate the same environment and exercise their role. Current knowledge suggests possible links of these bacteria with gastroduodenal diseases, such as peptic ulcer and gastric cancer but most of them need further scientific evidence. This review summarizes current information on these complex interrelations between gastric microbial communities and host in health and disease.

scholarly journals The Acute Effects of Exercise and Temperature on Regional mtDNA

2021 ◽  
Vol 18 (12) ◽  
pp. 6382
Author(s):  
Mark L. McGlynn ◽  
Halee Schnitzler ◽  
Robert Shute ◽  
Brent Ruby ◽  
Dustin Slivka
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Current Knowledge ◽  
Vastus Lateralis ◽  
Fold Change ◽  
Acute Effects ◽  
Ambient Conditions ◽  
Mtdna Copy Number ◽  
Post Exercise ◽  
Ambient Temperatures

A reduced mitochondrial DNA (mtDNA) copy number, the ratio of mitochondrial DNA to genomic DNA (mtDNA:gDNA), has been linked with dysfunctional mitochondria. Exercise can acutely induce mtDNA damage manifested as a reduced copy number. However, the influence of a paired (exercise and temperature) intervention on regional mtDNA (MINor Arc and MAJor Arc) are unknown. Thus, the purpose of this study was to determine the acute effects of exercise in cold (7 °C), room temperature (20 °C), and hot (33 °C) ambient temperatures, on regional mitochondrial copy number (MINcn and MAJcn). Thirty-four participants (24.4 ± 5.1 yrs, 87.1 ± 22.1 kg, 22.3 ± 8.5 %BF, and 3.20 ± 0.59 L·min−1 VO2peak) cycled for 1 h (261.1 ± 22.1 W) in either 7 °C, 20 °C, or 33 °C ambient conditions. Muscle biopsy samples were collected from the vastus lateralis to determine mtDNA regional copy numbers via RT-qPCR. mtDNA is sensitive to the stressors of exercise post-exercise (MIN fold change, −1.50 ± 0.11; MAJ fold change, −1.70 ± 0.12) and 4-h post-exercise (MIN fold change, −0.82 ± 0.13; MAJ fold change, −1.54 ± 0.11). The MAJ Arc seems to be more sensitive to heat, showing a temperature-trend (p = 0.056) for a reduced regional copy number ratio after exercise in the heat (fold change −2.81 ± 0.11; p = 0.019). These results expand upon our current knowledge of the influence of temperature and exercise on the acute remodeling of regional mtDNA.

scholarly journals Mechanisms of Human Mitochondrial DNA Maintenance: The Determining Role of Primary Sequence and Length over Function

1999 ◽  
Vol 10 (10) ◽  
pp. 3345-3356 ◽  
Author(s):  
Carlos T. Moraes ◽  
Lesley Kenyon ◽  
Huiling Hao
Keyword(s):  
Mitochondrial Dna ◽  
Oxidative Phosphorylation ◽  
Copy Number ◽  
Human Cells ◽  
Mtdna Copy Number ◽  
Molecular Features ◽  
Mtdna Replication ◽  
Selection For ◽  
Dna Maintenance

Although the regulation of mitochondrial DNA (mtDNA) copy number is performed by nuclear-coded factors, very little is known about the mechanisms controlling this process. We attempted to introduce nonhuman ape mtDNA into human cells harboring either no mtDNA or mutated mtDNAs (partial deletion and tRNA gene point mutation). Unexpectedly, only cells containing no mtDNA could be repopulated with nonhuman ape mtDNA. Cells containing a defective human mtDNA did not incorporate or maintain ape mtDNA and therefore died under selection for oxidative phosphorylation function. On the other hand, foreign human mtDNA was readily incorporated and maintained in these cells. The suicidal preference for self-mtDNA showed that functional parameters associated with oxidative phosphorylation are less relevant to mtDNA maintenance and copy number control than recognition of mtDNA self-determinants. Non–self-mtDNA could not be maintained into cells with mtDNA even if no selection for oxidative phosphorylation was applied. The repopulation kinetics of several mtDNA forms after severe depletion by ethidium bromide treatment showed that replication and maintenance of mtDNA in human cells are highly dependent on molecular features, because partially deleted mtDNA molecules repopulated cells significantly faster than full-length mtDNA. Taken together, our results suggest that mtDNA copy number may be controlled by competition for limiting levels of trans-acting factors that recognize primarily mtDNA molecular features. In agreement with this hypothesis, marked variations in mtDNA levels did not affect the transcription of nuclear-coded factors involved in mtDNA replication.

Nucleosome dynamics

2006 ◽  
Vol 73 ◽  
pp. 109-119 ◽  
Author(s):  
Chris Stockdale ◽  
Michael Bruno ◽  
Helder Ferreira ◽  
Elisa Garcia-Wilson ◽  
Nicola Wiechens ◽  
...  
Keyword(s):  
High Resolution ◽  
Chromatin Structure ◽  
Current Knowledge ◽  
Dynamic Properties ◽  
Structure And Dynamics ◽  
Nucleosome Dynamics ◽  
Sharp Focus ◽  
Recent Advances ◽  
Insight Into ◽  
Chromatin Structure And Dynamics

In the 30 years since the discovery of the nucleosome, our picture of it has come into sharp focus. The recent high-resolution structures have provided a wealth of insight into the function of the nucleosome, but they are inherently static. Our current knowledge of how nucleosomes can be reconfigured dynamically is at a much earlier stage. Here, recent advances in the understanding of chromatin structure and dynamics are highlighted. The ways in which different modes of nucleosome reconfiguration are likely to influence each other are discussed, and some of the factors likely to regulate the dynamic properties of nucleosomes are considered.

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