• 한국생물공학회:학술대회논문집
• /
• 2005.10a
• /
• pp.868-869
• /
• 2005

• 한국생물공학회:학술대회논문집
• /
• 2005.10a
• /
• pp.916-916
• /
• 2005

• 한국생물공학회:학술대회논문집
• /
• 2005.10a
• /
• pp.225-225
• /
• 2005

• BMB Reports
• /
• v.29 no.4
• /
• pp.300-307
• /
• 1996

ATP and ADP are potential regulators of mitochondtial respiration and at physiological concentrations they affect the rate of electron transfer between cytochrome c and cytochrome c oxidase. The electron transfer, however, depends on the electrostatic interaction between the two proteins. In order to exclude any nonspecific ionic effects by these polyvalent nucleotides, we used 2'-O-(2,4,6)trinitro(TNP)-derivatives of ATP and ADP which have three orders of magnitude higher affinity for cytochrome c oxidase. A simple titration of the fluorescence intensity of TNP by cytochrome c oxidase showed a binding stoichiometry of 2:1 cytochrome c:cytochrome c oxidase. Higher ionic strength was required for TNP-ATP than for TNP-ADP to be dissociated from cytochrome c oxidase, indicating that the negative charges on the phosphate group are at least partially responsible for the binding. In both spectrophotometric and polarographic assays, addition of ATP (and ADP to a less extent) showed an enhanced cytochrome c oxidase activity. Both electron paramagnetic resonance and fluorescence spectra indicate that there is no Significant change in the cytochrome c-cytochrome c oxidase interaction. Instead, reduction levels of the cytochromes at steadystate suggest that the increased activity of nucleotide-bound cytochrome c oxidase is due to faster electron transfer from cytochrome ${\alpha}$ to cytochrome ${\alpha}_3$, which is known to be the fate limiting step in the oxygen reduction by cytochrome c oxidase.

• BMB Reports
• /
• v.48 no.10
• /
• pp.539-540
• /
• 2015

It has been proposed that the selective elimination of cancer stem cells (CSCs) using targeted therapy could greatly reduce tumor growth, recurrence, and metastasis. To develop effective therapeutic targets for CSC elimination, we aimed to define the properties of CSC mitochondria, and identify CSC-mitochondria-specific targets in colon cancer. We found that colon CSCs utilize mitochondrial oxidative phosphorylation (OXPHOS) to produce ATP. We also found that forkhead box protein 1 (FOXM1)-induced peroxiredoxin 3 (PRDX3) maintains the mitochondrial function, and the FOXM1/PRDX3 mitochondrial pathway maintains survival of colon CSCs. Furthermore, FOXM1 induces CD133 (PROM1/prominin 1) expression, which maintains the stemness of colon CSCs. Together, our findings indicate that FOXM1, PRDX3, and CD133 are potential therapeutic targets for the elimination of CSCs in colon cancer.

• Biomolecules & Therapeutics
• /
• v.18 no.3
• /
• pp.235-245
• /
• 2010

Mitochondria have long been recognized as ATP engines for the cell and recently as a dynamic and mobile organelles that control cell death and life. This exquisite organelle is the site of reactive oxygen species production and is highly vulnerable to exogenous stresses, resulting in catastrophic damage to the cell. Mitochondrial dysfunction is linked to a wide range of age-associated degenerative diseases, such as metabolic syndrome, cardiovascular disease, and neurodegenerative diseases. Understanding the molecular mechanisms of mitochondria-dependent pathogenesis may provide important strategies to treat these diseases. Indeed, mitochondria are emerging therapeutic targets for the mitochondria-related diseases. In this paper, we review the recent concepts of mitochondrial biology and how mitochondria are involved in age-associated degenerative diseases. Furthermore, we summarize the therapeutics which target to improve mitochondrial functions.

• International Journal of Oral Biology
• /
• v.42 no.3
• /
• pp.85-90
• /
• 2017

Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide ($NAD^+$) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.

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

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.6
• /
• pp.567-577
• /
• 2017

Obesity is known to induce inhibition of glucose uptake, reduction of lipid metabolism, and progressive loss of skeletal muscle function, which are all associated with mitochondrial dysfunction in skeletal muscle. Mitochondria are dynamic organelles that regulate cellular metabolism and bioenergetics, including ATP production via oxidative phosphorylation. Due to these critical roles of mitochondria, mitochondrial dysfunction results in various diseases such as obesity and type 2 diabetes. Obesity is associated with impairment of mitochondrial function (e.g., decrease in $O_2$ respiration and increase in oxidative stress) in skeletal muscle. The balance between mitochondrial fusion and fission is critical to maintain mitochondrial homeostasis in skeletal muscle. Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion and fission by favorably shifting fission or reducing fusion proteins. Mitophagy is the catabolic process of damaged or unnecessary mitochondria. Obesity reduces mitochondrial biogenesis in skeletal muscle and increases accumulation of dysfunctional cellular organelles, suggesting that mitophagy does not work properly in obesity. Mitochondrial dysfunction and oxidative stress are reported to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in skeletal muscle. It is well known that exercise is the most effective intervention to protect against obesity. Although the cellular and molecular mechanisms by which exercise protects against obesity-induced mitochondrial dysfunction in skeletal muscle are not clearly elucidated, exercise training attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in obese skeletal muscle.

• Biomolecules & Therapeutics
• /
• v.12 no.1
• /
• pp.25-33
• /
• 2004

In this study we investigated whether ATP loss was involved in the potentiated death of immunostimulated rat primary astrocytes in glucose-deprived condition. Rat primary astrocytes immunostimulated with LPS plus IFN-${\gamma}$ for 48 h underwent death upon glucose deprivation, which dependent on the production of peroxynitrite. Intracellular ATP level synergistically decreased by glucose deprivation in immunostimulated astrocytes but not in control cells, and the loss of ATP occurred well ahead of the LDH release. The synergistic cell death and ATP loss by immunostimulation and glucose deprivation were inhibited by iNOS inhibitor (L-NAME and L-NNA) or peroxynitrite decomposition catalyst (also a superoxide anion scavenger), Mn(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (MnTMPyP). Exogenous addition of peroxynitrite generator, SIN-l timedependently induced ATP loss and cell death in the glucose-deprived astrocytes. Depletion of intracellular glutathione (GSH) and dis겨ption of mitochondrial transmembrane potential (MTP) were also observed under same conditions. Supply cellular ATP by the addition of exogenous adenosine or ATP during glucose deprivation inhibited ATP depletion, GSH depletion, MTP disruption and cell death in SIN-l treated or immunostimulated astrocytes. This study showed that perturbation in the regulation of intracellular ATP level in immunostimulated astrocytes might make them more vulnerable to energy challenging stimuli.