• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.23-30
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• 2008

Mitochondria biogenesis requires a coordination of two genomes, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Disruption of mitochondria function leads to a loss of mitochondrial membrane potential and ATP generating capacity and consequently results in chronic degenerative diseases including insulin resistance, metabolic syndrome and neurodegenerative diseases. Although PPAR-${\gamma}$ coactivator-$1{\alpha}$ (PGC-$1{\alpha}$) was discovered as a central regulator of mitochondria biogenesis and a transcriptional co-activator of nuclear respiratory factor (NRF) and mitochondrial transcription factor A (Tfam), the expressions of PGC-$1{\alpha}$, NRF and Tfam were not significantly altered in tissues showing abnormal mitochondria functions. This observation suggests that there should be another regulator(s) for mitochondria function. Here, we demonstrate microRNAs (miRNAs) can modulate mitochondria function. Overexpression of microRNA dissipated mitochondrial membrane potential and increased ROS production in vitro and in vivo. It will be discussed the target of microRNA and its role in metabolic syndrome.

• Biomedical Science Letters
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• v.26 no.4
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• pp.336-343
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• 2020

The present study was carried out to investigate the possibility that bispidinone derivative makes anticancer drug availability to human cervical carcinoma cell. The B8 has the lowest IC50 value among B8, B9 and B10 which are bispidinone analogue with bromide. According to cytotoxic test through WST-8 assay, B8 shows the most magnificent cytotoxicity effectiveness with 76 μM of IC50 value. In human cervical carcinoma cell treated with B8, it noticeably controlled cellular multiplication by increase of concentration and time. Furthermore, morphological changes like cellular shrink, disruption and nuclear condensation, feature of apoptosis, are observed. Annexin V-FITC/PI double staining assay test proved that B8 can cause apoptosis. Moreover, after treatment with 76 μM of B8, flow cytometry analysis shows that increase of active oxygen species are induced and membrane potential in mitochondria is decreased. Manifestation of Bcl-2 family and caspase cascades protein provides evidence that B8 induces apoptosis through mitochondria and caspase-related pathway. Taken together, we suggested that B8 reduced membrane potential in mitochondria and induce apoptosis through the pathway depended on mitochondria and caspase.

• Applied Biological Chemistry
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• v.28 no.4
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• pp.271-277
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• 1985

A polarograph with specially designed cell compartment usable in kinetic study of the mitochondrial respiration of a small sized sample was made, and its performance and experimental conditions were examined. An applied potential (ca-1.2V vs. SCE) which gives rise to the second step reduction of oxygen caused a considerable level of a residual current independent of oxygen, which is temporarily interpreted as the reduction current of the membrane-bound redox material(s) of mitochondria. A potential corresponding to the first slop reduction of oxygen (ca-0.4V vs SCE) did not produce the residual current. Thus, it is suggested that a measurement of oxygen concentration in a sample of mitochondria and submitochondrial particles by using dropping mercury electrode should be done with an applied potential of about -0.4V vs SCE. Consumption of oxygen by mitochondria was observed to follow practically zero order kinetics. Its rate constant exhibited the proportional relationship with the respiratory activity of mitochondria. Usefulness of tile instrument was properly demonstrated in the work on the temperature effect on the respiration of mitochondria isolated from several plant 4issues which were selected on the basis of chilling susceptivity.

• BMB Reports
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• v.44 no.8
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• pp.517-522
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• 2011

Mitochondrial dynamics not only involves mitochondrial morphology but also mitochondrial biogenesis, mitochondrial distribution, and cell death. To identify specific regulators to mitochondria dynamics, we screened a chemical library and identified niclosamide as a potent inducer of mitochondria fission. Niclosamide promoted mitochondrial fragmentation but this was blocked by down-regulation of Drp1. Niclosamide treatment resulted in the disruption of mitochondria membrane potential and reduction of ATP levels. Moreover, niclosamide led to apoptotic cell death by caspase-3 activation. Interestingly, niclosamide also increased autophagic activity. Inhibition of autophagy suppressed niclosamide-induced cell death. Therefore, our findings suggest that niclosamide induces mitochondria fragmentation and may contribute to apoptotic and autophagic cell death.

• BMB Reports
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• v.51 no.11
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• pp.549-556
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• 2018

Mitochondria are ubiquitous and multi-functional organelles involved in diverse metabolic processes, namely energy production and biomolecule synthesis. The intracellular mitochondrial morphology and distribution change dynamically, which reflect the metabolic state of a given cell type. A dramatic change of the mitochondrial dynamics has been observed in early development that led to further investigations on the relationship between mitochondria and the process of development. A significant developmental process to focus on, in this review, is a differentiation of neural progenitor cells into neurons. Information on how mitochondria-regulated cellular energetics is linked to neuronal development will be discussed, followed by functions of mitochondria and associated diseases in neuronal development. Lastly, the potential use of mitochondrial features in analyzing various neurodevelopmental diseases will be addressed.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.11-11
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• 2001

In this study, we examined the developmental potential of reconstructed bovine embryos and the fate of donor mitochondria during their preimplantation development after nuclear transfer. Isolated cumulus cells were used as donor cells in nuclear transfer. Cumulus cells labelled with MitoTracker Green FM fluorochrome were injected into enucleated bovine MII oocytes and cultured in vitro. MitoTracker labelling on donor cells did not have a detrimental effect on blastocyst formation following nuclear transfer. Cleavage rate was about 69%(56/81) and blastocyst formation rate was 6.2% (5/81) at 7 days after nuclear transfer. The labelled mitochondria dispersed to the cytoplasm and became distributed among blastomeres and could be identified up to the 8- to 15-cell stages. Small patches of mitochondria were detected in some 8- to 15-cell stage embryos (5/20). However, donor mitochondria were not detected in embryos at the 16-cell stage and subsequent developmental stages. In the control group, mitochondria could be identified in arrested 1-cell embryos up to 7 days after nuclear transfer These results suggest that donor mitochondria disappear from recipient cytoplasm before 16-cell stage following nuclear transfer in reconstructed bovine embryos.

• BMB Reports
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• v.42 no.11
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• pp.719-724
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• 2009

Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

• Animal cells and systems
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• v.8 no.2
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• pp.97-103
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• 2004

The cytotoxic effect of iron was examined in peritoneal macrophage to determine contributing factors by iron injection to rat. Viability was reduced by 24% by the iron-overload and by 30% by short-term iron addition. Total iron was increased by 45% in the iron-overloaded with remarkable elevation (9 to 14 fold) in the presence of $FeSO_4$. Free calcium was also increased by 19% in control and 44% in iron-overloaded group due to additional $FeSO_4$ NO and MDA were increased by 40% and 136%, respectively, with significant reduction (37%) of NAD(P)H. RCR and cytochrome c oxidase activity were lowered approximately by 10% with reduction of mitochondrial membrane potential. Addition of iron was frequently associated with altered distribution of mitochondria of high membrane potential in the iron-overloaded macrophage. These results suggest altered mitochondria with high NO and low NAD(P)H due to iron.

• Biomolecules & Therapeutics
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• v.22 no.6
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• pp.519-524
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• 2014

We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a trans-stilbene analogue, induces apoptosis in human cancer cells. However, the detailed mechanisms of mitochondria-dependent apoptosis induced by TMS are not fully understood. In the present study, the possible roles of annexin A5 in TMS-mediated apoptosis were investigated in MCF7 human breast cancer cells. Quantitative real-time PCR analysis and Western blot analysis showed that the expression of annexin A5 was strongly increased in TMS-treated cells. TMS caused a strong translocation of annexin A5 from cytosol into mitochondria. Confocal laser scanning microscopic analysis clearly showed that TMS induced translocation of annexin A5 into mitochondria. TMS increased the expression and oligomerization of voltage-dependent anion channel (VDAC) 1, which may promote mitochondria-dependent apoptosis through disruption of mitochondrial membrane potential. When cells were treated with TMS, the levels of Bax, and Bak as well as annexin A5 were strongly enhanced. Moreover, we found that the cytosolic release of apoptogenic factors such as cytochrome c, or apoptosis-inducing factor (AIF) in mitochondria was markedly increased. Annexin A5 depletion by siRNA led to decreased proapoptotic factors such as Bax, Bak, and annexin A5. Taken together, our results indicate that annexin A5 may play an important role in TMS-mediated mitochondrial apoptosis through the regulation of proapoptotic proteins and VDAC1 expression.

• Exercise Science
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• v.26 no.3
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• pp.229-237
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• 2017

PURPOSE: This study was to investigate the Glycolysis mediated sarcoplasmic reticulum (SR) $Ca^{2+}$ signal regulates mitochondria $Ca^{2+}$ during skeletal muscle contraction by using glycolysis inhibitor. METHODS: To examine the effect of Glycolysis inhibitor on SR and mitochondria $Ca^{2+}$ content, we used skeletal muscle fiber from gastrocnemius muscle. 2-deoxy glucose and 3-bromo pyruvate used as glycolysis inhibitor, it applied to electrically stimulated muscle contraction experiment. Intracellular $Ca^{2+}$ content, SR, mitochondria $Ca^{2+}$ level and mitochondria membrane potential (MMP) was detected by confocal microscope. Mitochondrial energy metabolism related enzyme, citric acid synthase activity also examined for mitochondrial function during the muscle contraction. RESULTS: Treatment of 2-DG and 3BP decreased the muscle contraction induced SR $Ca^{2+}$ increase however the mitochondria $Ca^{2+}$ level was increased by treatment of inhibitors and showed and overloading as compared with the control group. Glycolysis inhibitor and thapsigargin treatment showed a significant decrease in MPP of skeletal muscle cells compared to the control group. CS activity significantly decreased after pretreatment of glycolysis inhibitor during skeletal muscle contraction. These results suggest that regulation of mitochondrial $Ca^{2+}$ levels by glycolysis is an important factor in mitochondrial energy production during skeletal muscle contraction CONCLUSIONS: These results suggest that mitochondria $Ca^{2+}$ level can be regulated by SR $Ca^{2+}$ level and glycolytic regulation of intraocular $Ca^{2+}$ signal play pivotal role in regulation of mitochondria energy metabolism during the muscle contraction.