• Interdisciplinary Bio Central
• /
• v.1 no.2
• /
• pp.7.1-7.7
• /
• 2009

"To be, or not to be?" This question is not only Hamlet's agony but also the dilemma of mitochondria in a cancer cell. Cancer cells have a high glycolysis rate even in the presence of oxygen. This feature of cancer cells is known as the Warburg effect, named for the first scientist to observe it, Otto Warburg, who assumed that because of mitochondrial malfunction, cancer cells had to depend on anaerobic glycolysis to generate ATP. It was demonstrated, however, that cancer cells with intact mitochondria also showed evidence of the Warburg effect. Thus, an alternative explanation was proposed: the Warburg effect helps cancer cells harness additional ATP to meet the high energy demand required for their extraordinary growth while providing a basic building block of metabolites for their proliferation. A third view suggests that the Warburg effect is a defense mechanism, protecting cancer cells from the higher than usual oxidative environment in which they survive. Interestingly, the latter view does not conflict with the high-energy production view, as increased glucose metabolism enables cancer cells to produce larger amounts of both antioxidants to fight oxidative stress and ATP and metabolites for growth. The combination of these two different hypotheses may explain the Warburg effect, but critical questions at the mechanistic level remain to be explored. Cancer shows complex and multi-faceted behaviors. Previously, there has been no overall plan or systematic approach to integrate and interpret the complex signaling in cancer cells. A new paradigm of collaboration and a well-designed systemic approach will supply answers to fill the gaps in current cancer knowledge and will accelerate the discovery of the connections behind the Warburg mystery. An integrated understanding of cancer complexity and tumorigenesis is necessary to expand the frontiers of cancer cell biology.

• Microbiology and Biotechnology Letters
• /
• v.50 no.3
• /
• pp.414-421
• /
• 2022

In this study, we isolated Weizmannia ginsengihumi LGHNH (KCTC 14462BP) from 30-year-old wild Panax ginseng C.A. Meyer and elucidated the characteristics of the isolated bacterium and its industrial potential as an anti-aging material. W. ginsengihumi LGHNH was investigated to produce indole-3-acetic acid (IAA), a plant growth-promoting hormone (1.38 ㎍/ml to 2.22 ㎍/ml). We also confirmed the existence of bioconversion activity via the comparison of the ginsenoside content before and after fermentation. As for the converted minor ginsenoside, Rg2(R), Rg4, Rg6, Rg3(S), Rg3(R), Rk1, Rg5, Rh1(R), Rk3 and Rh4 are known to have high bioavailability and various skin effects. We measured mitochondrial membrane potential and ATP biosynthesis to elucidate W. ginsengihumi LGHNH cultured product (WCP) as an anti-aging material. As a result, the mitochondrial membrane potential in HaCaT cells with UVB decreased to 39.3% compared to the unirradiated group, but was recovered to 57.3% and 58.1% by 0.001% (v/v) and 0.01% (v/v) WCP, respectively. In addition, we measured mitochondrial ATP biosynthesis. It decreased to 94.3% compared to the unirradiated group with UVB, but was recovered to 105.3% and 105.7% by 0.001% (v/v) and 0.01% (v/v) WCP.

• Journal of Korean Neurosurgical Society
• /
• v.59 no.3
• /
• pp.259-268
• /
• 2016

Objective : Accumulation of advanced glycation end-products (AGE) and mitochondrial glycation is importantly implicated in the pathological changes of the brain associated with diabetic complications, Alzheimer disease, and aging. The present study was undertaken to determine whether sildenafil, a type 5 phosphodiesterase type (PDE-5) inhibitor, has beneficial effect on neuronal cells challenged with AGE-induced oxidative stress to preserve their mitochondrial functional integrity. Methods : HT-22 hippocampal neuronal cells were exposed to AGE and changes in the mitochondrial functional parameters were determined. Pretreatment of cells with sildenafil effectively ameliorated these AGE-induced deterioration of mitochondrial functional integrity. Results : AGE-treated cells lost their mitochondrial functional integrity which was estimated by their MTT reduction ability and intracellular ATP concentration. These cells exhibited stimulated generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, induction of mitochondrial permeability transition, and release of the cytochrome C, activation of the caspase-3 accompanied by apoptosis. Western blot analyses and qRT-PCR demonstrated that sildenafil increased the expression level of the heme oxygenase-1 (HO-1). CoPP and bilirubin, an inducer of HO-1 and a metabolic product of HO-1, respectively, provided a similar protective effects. On the contrary, the HO-1 inhibitor ZnPP IX blocked the effect of sildenafil. Transfection with HO-1 siRNA significantly reduced the protective effect of sildenafil on the loss of MTT reduction ability and MPT induction in AGE-treated cells. Conclusion : Taken together, our results suggested that sildenafil provides beneficial effect to protect the HT-22 hippocampal neuronal cells against AGE-induced deterioration of mitochondrial integrity, and upregulation of HO-1 is involved in the underlying mechanism.

• Biomolecules & Therapeutics
• /
• v.27 no.1
• /
• pp.48-53
• /
• 2019

Reactive oxygen species (ROS) are widely generated in biological processes such as normal metabolism and response to xenobiotic exposure. While ROS can be beneficial or harmful to cells and tissues, generation of ROS by diverse anti-cancer drugs or phytochemicals plays an important role in the induction of apoptosis. We recently identified a derivative of naphthalene, MS-5, that induces apoptosis of an ovarian cell, CAOV-3. Interestingly, MS-5 induced apoptosis by down-regulating the ROS. Cell viability was evaluated by water-soluble tetrazolium salt (WST-1) assay. Apoptosis was evaluated by flow cytometry analysis. Intracellular ROS ($H_2O_2$), mitochondrial superoxide, mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was assessed by western blotting. The level of ATP was measured using ATP Colorimetric/Fluorometric Assay kit. MS-5 inhibited growth of ovarian cancer cell lines, CAOV-3, in a concentration- and time-dependent manner. MS-5 also induced G1 cell cycle arrest in CAOV-3 cells, while MS-5 decreased intracellular ROS generation. In addition, cells treated with MS-5 showed the decrease in MMP and ATP production. In this study, we found that treatment with MS-5 in CAOV-3 cells induced apoptosis but decreased ROS level. We suspect that MS-5 might interfere with the minimum requirements of ROS for survival. These perturbations appear to be concentration-dependent, suggesting that MS-5 may induce apoptosis by interfering with ROS generation. We propose that MS-5 may be a potent therapeutic agent for inducing apoptosis in ovarian cancer cell through regulation of ROS.

• The Korean Journal of Mycology
• /
• v.21 no.3
• /
• pp.165-171
• /
• 1993

The effects of the iron ions for the light-induced mitochondrial $F_0F_1-ATPase$ of Lentinus edodes was studied. The enzyme activity was stimulated up to 202% by 0.1 mM $Fe^{2-}$ ion, but was inhibited by $Fe^{3+}\;and\;Mg^{2+}$. In the presence of 0.5 mM $Mg^{2+}$, the activity also increased 32% by 0.1 mM $Fe^{2+}$ ion, and decreased to a similar extent by $Fe^{3+}$ ion than by only $Fe^{3+}$ ion. Also, the activity was inhibited 53% by 5.0 mM $Fe^{2-}$ ion in the presence of 0.5 mM $Mg^{2+}$ ion and various concentration of $Fe^{3+}$ ion(mM). These results showed that $Fe^{2+}$ strongly stimulated the enzyme activity and its role for the enzyme was independent of $Mg^{2+}$ ion, but was dependent of $Fe^{3+}$ ion. From inactivation of the enzyme by addition of metal chelating agent, EDTA, it is suggested that the enzyme is to be metalloenzyme. The optimal pH and temperature of the enzyme in the presence of 0.1 mM $Fe^{2+}$ was 7.6 and $63^{\circ}C$, respectively.

• Korean Journal of Food Science and Technology
• /
• v.49 no.6
• /
• pp.685-692
• /
• 2017

Mitochondrial biogenesis-a process that leads to an increment in the number and density of mitochondria, improves physical performance and body health by enhancing exercise capacity. In the present study, we investigated the stimulatory effect of Ashitaba and red ginseng complex (ARC) on exercise capacity in L6 skeletal muscle cells and mice. In L6 skeletal muscle cells, ARC increased the mitochondrial contents and ATP production by activating AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-$1{\alpha}$) and up-regulating the mRNA expression of nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM). In the animal experiments, mice treated with ARC showed an increment in exercise capacity as compared with mice treated with Ashitaba extract or red ginseng extract alone. These studies indicate that ARC might serve as a potential natural candidate for enhancing exercise capacity by stimulation of mitochondrial biogenesis.

• Biomedical Science Letters
• /
• v.14 no.4
• /
• pp.239-242
• /
• 2008

Obesity results from a combination of genetic, environmental, and behavioral factors. Uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCP separates oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCP facilitates the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. Therefore, we investigated the genotype for the G>A polymorphism at the position -866 of UCP2 gene in Koreans and compared genotype of patients with control group. 50 patients (Male 22, Female 28), who previously underwent type 2 diabetcs (T2DM) and 30 controls (Male 14, Female 16) participated in this study. There was a weak significant association between -866 G>A polymorphism in UCP2 gene and T2DM. The present study shows that UCP2 -866 G>A polymorphism may not be associated with the pathogenesis of T2DM as opposed to the previous reports in other countries. Further studies with larger population may be needed for the development of diagnostic methods at genetic level such as DNA chip.

• Proceedings of the Microbiological Society of Korea Conference
• /
• 2002.10a
• /
• pp.76-78
• /
• 2002

Heat shock proteins (HSPs) are induced in most living cells by mild heat treatment, ethanol, heavy metal ions and hypoxia. In yeast Saccharomyces cerevisiae, mild heat pretreatment strongly induces Hsp104 and thus provide acquired thermotolerance. The ability of hsp104 deleted mutant $({\triangle}hsp104)$ to acquire tolerance to extreme temperature is severely impaired. In providing thermotolerance, two ATP binding domains are indispensible, as demonstrated in ClpA and ClpB proteases of E. coli. The mechanisms by which Hsp104 protects cells from severe heat stress are not yet completely elucidated. We have investigated regulation of mitochondrial metabolic pathways controlled by the functional Hsp104 protein using $^{13}C_NMR$ spectroscopy and observed that the turnover rate of TCA cycle was enhanced in the absence of Hsp104. Production of ROS, which are toxic to kill cells radiply via oxidative stress, was also examined by fluorescence assay. Mitochondrial dysfunction was manifested in increased ROS levels and higher sensitivity for oxidative stress in the absence of Hsp104 protein expressed. Finally, we have identified mitochondrial complex I and Ferritin as binding protein(s) of Hsp104 by yeast two hybrid experiment. Based on these observations, we suggest that Hsp104 protein functions as a protector of oxidative stress via either keeping mitochondrial integrity, direct binding to mitochonrial components or regulating metal-catalyzed redox chemistry.

• Proceedings of the Korean Society of Crop Science Conference
• /
• 2017.06a
• /
• pp.126-126
• /
• 2017

Mitochondria are important in wheat, as in all crops, as the main source of ATP for cell maintenance and growth including vitamin synthesis, amino acid metabolism and photorespiration. To investigate the mitochondrial proteome of the roots of wheat seedlings, a systematic and targeted analysis were carried out on the mitochondrial proteome from 15 day-old wheat seedling root material. Mitochondria were isolated by Percoll gradient centrifugation; and extracted proteins were separated and analyzed by Tricine SDS-PAGE along with LTQ-FTICR mass spectrometry. From the isolated the sample, 184 proteins were identified which is composed of 140 proteins as mitochondria and 44 proteins as other subcellular proteins that are predicted by the freeware subcellular predictor. The identified proteins in mitochondria were functionally classified into 12 classes using the ProtFun 2.2 server based on biological processes. Proteins were shown to be involved in amino acid biosynthesis (17.1%), biosynthesis of cofactors (6.4%), cell envelope (11.4%), central intermediary metabolism (10%), energy metabolism (20%), fatty acid metabolism (0.7%), purines and pyrimidines (5.7%), regulatory functions (0.7%), replication and transcription (1.4%), translation (22.1%), transport and binding (1.4%), and unknown (2.8%). These results indicate that many of the protein components present and functions of identifying proteins are common to other profiles of mitochondrial proteins performed to date. This dataset provides the first extensive picture, to our knowledge, of mitochondrial proteins from wheat roots. Future research is required on quantitative analysis of the wheat mitochondrial proteomes at the spatial and developmental level.

• Preventive Nutrition and Food Science
• /
• v.5 no.4
• /
• pp.230-233
• /
• 2000

The present work was designed to determine whether change in fluidity of the mitochondrial membrane affects mitochondrial {TEX}$F_{1}${/TEX}{TEX}$F_{0}${/TEX}ATPase characteristics in NIDDM-prone BHE/Cdb rat. Isolated mitochondria fom BHE/Cdb rat fed a 6% coconut oil or corn oil were functionally tested by an analysis of its respiration and the coupling of this process to ATP synthesis in presence of oligomycin, a specific inhibitor of oxidative phosphorylation (OXPHOS), that binds to the {TEX}$F_{1}${/TEX}{TEX}$F_{0}${/TEX}ATPase. Mitochondria from rats fed coconut oil were more responsive to the inhibitory action of oligomycin with respect to state 3 respiration, respiratory control (RC) ratio and ADP:P (P/O) ratio than were mitochondria from rats fed corn oil. In state 3 respiration, mitochondria from rats fed coconut oil consumed less oxygen than did mitochondria from rats fed corn oil. RC ratio was lower in the mitochondria from rats fed coconut oil than was mitochondria from rats fed corn oil. In P/O ratio, the mitochondria from rats fed coconut oil had a lower P/O ratio than did mitochondria from rats fed corn oil. The data showed that the chang influidity of the mitochondrial membrane by dietary fat affected mitochondrial {TEX}$F_{1}${/TEX}{TEX}$F_{0}${/TEX}ATPase characteristics. The present study on diet differences in {TEX}$F_{1}${/TEX}{TEX}$F_{0}${/TEX}ATPase characteristics provides considerable insight into the role diets play in the control of mitochondrial function, expecially OXPHOS in NIDDM with mitochondrial defects.