scholarly journals Increased mtDNA copy number promotes cancer progression by enhancing mitochondrial oxidative phosphorylation in microsatellite-stable colorectal cancer

2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Xiacheng Sun ◽  
Lei Zhan ◽  
Yibing Chen ◽  
Gang Wang ◽  
Linjie He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Oxidative Phosphorylation ◽  
Cancer Progression ◽  
Copy Number ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Mtdna Copy Number

scholarly journals Ginsenosides Rb1 and Rg1 Protect Primary Cultured Astrocytes against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury via Improving Mitochondrial Function

2019 ◽  
Vol 20 (23) ◽  
pp. 6086 ◽  
Author(s):  
Meng Xu ◽  
Qing Ma ◽  
Chunlan Fan ◽  
Xue Chen ◽  
Huiming Zhang ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Cell Viability ◽  
Mitochondrial Function ◽  
Copy Number ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Ros Production ◽  
Protective Effects ◽  
Mtdna Copy Number ◽  
Cultured Astrocytes

This study aimed to evaluate whether ginsenosides Rb1 (20-S-protopanaxadiol aglycon) and Rg1 (20-S-protopanaxatriol aglycon) have mitochondrial protective effects against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in primary mouse astrocytes and to explore the mechanisms involved. The OGD/R model was used to mimic the pathological process of cerebral ischemia-reperfusion in vitro. Astrocytes were treated with normal conditions, OGD/R, OGD/R plus Rb1, or OGD/R plus Rg1. Cell viability was measured to evaluate the cytotoxicity of Rb1 and Rg1. Intracellular reactive oxygen species (ROS) and catalase (CAT) were detected to evaluate oxidative stress. The mitochondrial DNA (mtDNA) copy number and mitochondrial membrane potential (MMP) were measured to evaluate mitochondrial function. The activities of the mitochondrial respiratory chain (MRC) complexes I–V and the level of cellular adenosine triphosphate (ATP) were measured to evaluate oxidative phosphorylation (OXPHOS) levels. Cell viability was significantly decreased in the OGD/R group compared to the control group. Rb1 or Rg1 administration significantly increased cell viability. Moreover, OGD/R caused a significant increase in ROS formation and, subsequently, it decreased the activity of CAT and the mtDNA copy number. At the same time, treatment with OGD/R depolarized the MMP in the astrocytes. Rb1 or Rg1 administration reduced ROS production, increased CAT activity, elevated the mtDNA content, and attenuated the MMP depolarization. In addition, Rb1 or Rg1 administration increased the activities of complexes I, II, III, and V and elevated the level of ATP, compared to those in the OGD/R groups. Rb1 and Rg1 have different chemical structures, but exert similar protective effects against astrocyte damage induced by OGD/R. The mechanism may be related to improved efficiency of mitochondrial oxidative phosphorylation and the reduction in ROS production in cultured astrocytes.

scholarly journals Polymorphisms in the mitochondrial oxidative phosphorylation chain genes as prognostic markers for colorectal cancer

2012 ◽  
Vol 13 (1) ◽  
Author(s):  
Jesus Lascorz ◽  
Melanie Bevier ◽  
Witigo V Schönfels ◽  
Holger Kalthoff ◽  
Heiko Aselmann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Oxidative Phosphorylation ◽  
Prognostic Markers ◽  
Mitochondrial Oxidative Phosphorylation

scholarly journals Can Mitochondria DNA Provide a Novel Biomarker for Evaluating the Risk and Prognosis of Colorectal Cancer?

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Han Shuwen ◽  
Yang Xi ◽  
Pan Yuefen
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Copy Number ◽  
Controversial Issues ◽  
Mtdna Copy Number ◽  
Future Studies ◽  
Mtdna Variation ◽  
Mitochondria Dna ◽  
Prognosis Evaluation

Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate risk and prognosis evaluation could obtain better quality of life and longer survival time for the patients. Current research hotspot was focus on the gene biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA and regulates self-replicating so that it can be as a candidate biomarker for evaluating the risk and prognosis of colorectal cancer. But there were already huge controversies on this issue. The review was to summarize current viewpoints of the controversial issues and described our understanding from the four aspects including mtDNA copy number, mitochondrial displacement loop, mtDNA variation, and mtDNA microsatellite instability, wishing the summary of the mtDNA in colorectal cancer could provide a meaningful reference or a valuable direction in the future studies.

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.

scholarly journals Ordering copy number alteration data to analyze colorectal cancer progression

2012 ◽  
Vol 18 (B) ◽  
pp. 84
Author(s):  
Iuliana M. Bocicor ◽  
Giulio Caravagna ◽  
Alex Graudenzi ◽  
Claudia Cava ◽  
Giancarlo Mauri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Copy Number ◽  
Copy Number Alteration ◽  
Colorectal Cancer Progression

The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes

2006 ◽  
Vol 45 (1) ◽  
pp. 31-41 ◽  
Author(s):  
Chieu B. Diep ◽  
Kristine Kleivi ◽  
Franclim R. Ribeiro ◽  
Manuel R. Teixeira ◽  
Ole C. Lindgjaerde ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Copy Number ◽  
Meta Analysis ◽  
Colorectal Cancer Progression ◽  
Copy Number Changes ◽  
Genetic Events

scholarly journals Nuclear and mitochondrial genome responses in HeLa cells treated with inhibitors of mitochondrial DNA expression.

2006 ◽  
Vol 53 (3) ◽  
pp. 485-495 ◽  
Author(s):  
Janusz Piechota ◽  
Roman Szczesny ◽  
Kamila Wolanin ◽  
Aleksander Chlebowski ◽  
Ewa Bartnik
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Oxidative Phosphorylation ◽  
Hela Cells ◽  
Transcription Initiation ◽  
Copy Number ◽  
Mitochondrial Haplotype ◽  
Mtdna Copy Number ◽  
Atp Production ◽  
Bioenergetic Metabolism

The influence of mutations in the mitochondrial DNA (mtDNA) on the bioenergetic metabolism of the cell is still poorly understood. Many of the mutations in the mtDNA affect the expression of the mitochondrial genome. Investigations on cells from patients are not easy, especially as the mitochondrial DNA is heteroplasmic and this state is changed in culture. Moreover, the nuclear background and the mitochondrial haplotype may affect the behaviour of cells. Transfer of patient mitochondria to rho zero cell lines is also not optimal as these cells in general have many nuclear changes which may also affect cell behaviour. Thus, we decided to use inhibitors of mitochondrial genome expression, such as thiamphenicol, ethidium bromide and dideoxycytidine to investigate the bioenergetic metabolism of HeLa cells. We found that oxidative phosphorylation and glycolysis participate equally in ATP production in HeLa cells and that decreased activity of the respiratory chain leads to increased glycolysis and the reduction of cell growth. Insufficient ATP production in the oxidative phosphorylation process was not compensated by increased proliferation of the mitochondria. However, we were able to show that there are some mechanisms compensating limited expression of the mitochondrial genome within the mitochondria. Experiments with dideoxycytidine revealed that 10-fold decrease of the mtDNA copy number resulted in almost normal activity of cytochrome c oxidase. We found that mtDNA depletion is compensated mostly on the level of RNA metabolism in the mitochondria. Thus, our results are in agreement with the hypothesis that transcription initiation rather than mtDNA copy number is a rate limiting factor for expression of the mitochondrial genome.

Dependence of Platelet Adenyl Cyclase System on Oxidative Phosphorylation

1975 ◽  
Vol 34 (01) ◽  
pp. 042-049 ◽  
Author(s):  
Shuichi Hashimoto ◽  
Sachiko Shibata ◽  
Bokro Kobayashi
Keyword(s):  
Cyclic Amp ◽  
Oxidative Phosphorylation ◽  
Sodium Succinate ◽  
Potassium Cyanide ◽  
Adenyl Cyclase ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Adenyl Cyclase Activity ◽  
Intact Rabbit ◽  
Adenyl Cyclase System ◽  
Cyclic Amp Synthesis

SummaryThe radioactive adenosine 3′,5′-monophosphate (cyclic AMP) level derived from 8-14C adenine in intact rabbit platelets decreased in the presence of mitochondrial inhibitor (potassium cyanide) or uncoupler (sodium azide), and markedly increased by the addition of NaF, monoiodoacetic acid (MIA), or 2-deoxy-D-glucose. The stimulative effect of the glycolytic inhibitors was distinctly enhanced by the simultaneous addition of sodium succinate. MIA did neither directly stimulate the adenyl cyclase activity nor inhibit the phosphodiesterase activity. These results suggest that cyclic AMP synthesis in platelets is closely linked to mitochondrial oxidative phosphorylation.

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