PURPOSE: The purpose of this study is to evaluate the diagnostic availability of the morphology of mitochondria to identify the nature or the origin of neoplasms. MATRIALS AND METHODS: We analysed two cases of ovarian malignancy- a case of malignant steroid cell tumor, unclassified and a case of metastatic carcinosarcoma from the adrenal cortex- which were difficult to identify the origin and the nature of the tumor for special staining, immunohistochemical and ultrastructural methods. RESULTS: To evaluate the nature or the origin of neoplasms, we performed immuno histochemistry for various antigens and special stains, however the specific diagnostic clues were not provided by these modalities. The ultrastructural characteristics of mitochondria of neoplastic cells showing tubular or tubulo-vesicular inner mitochondrial membranes provided diagnostic clues as a marker for steroidogenic potential. The morphology of mitochondria is related to the enzyme activity and steroid-biosynthetic capacity of cells. Especially, the inner mitochondrial membrane structure is believed to be related to the steroid biosynthetic activity. In hypofunctional state of corticosteroid productian, a reduced number of inner mitochondrial membranes showing tubular patterns is noted. In cantrast, the stimulation of steroidogenesis result in a progressive increase of mitochondrial membrane showing densely packed rounded vesicular patterns via tubulo-vesicular patterns according to the activity of steroidogenesis. CONCLUSION: The tubular, the vesicular and the tubulo-vesicular mitochondria will be valuable to identify the uncertainty of nature and origin of tumor as a stemidogenic.
Carcinosarcoma ; Coloring Agents ; Diagnosis* ; Mitochondria ; Mitochondrial Membranes ; Uncertainty

PURPOSE: Lipophilic cations including tetraphenylphosphonium (TPP) salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes, resulting in accumulation in mitochondria in response to the negative inner transmembrane potentials. The development of radiolabeled phosphonium cations as a noninvasive imaging agent may serve as a new molecular "voltage sensor" probe to investigate the role of mitochondria in the pathophysiology and diagnosis of cancer. MATERIALS AND METHODS: We have synthesized a reference compound (4-fluorophenyl)triphenylphosphonium (TPP) and a labeled compound [18F]TPP via two step nucleophilic substitution of no-carrier-added [18F]fluoride with the precursor, 4-iodophenyltrimethylammonium iodide, in the presence of Kryptofix-2.2.2 and K2CO3. RESULT: The reference compound (4-fluorophenyl)triphenylphosphonium (TPP) was synthesized in 60% yield. The radiolabeled compound [18F]TPP was synthesized in 10~15% yield. The radiochemical purity of the [18F]TPP was 95.57+/-0.51% (n=11). CONCLUSION: [18F]TPP was successfully synthesized that might have a potential to be utilized as a novel myocardial or cancer imaging agent for PET. However, it is required to improve the radiochemical yield to apply [18F]TPP in preclinical or clinical researches.
Cations ; Diagnosis ; Membrane Potential, Mitochondrial ; Membrane Potentials ; Mitochondria ; Mitochondrial Membranes ; Plasma ; Salts

The mitochondrial respiratory chain supercomplex (mitoSC) is a complex super-assembly formed by free complexes on the mitochondrial inner membrane respiratory chain through the interaction between their subunits, mainly including mitoSCI+III+IV, mitoSCI+III, mitoSCIII+IV, high molecular weight mitoSC (HMW mitoSC) and mitochondrial metacomplex (mitoMC). mitoSC has been shown to improve the efficiency of electron transport in the respiratory chain and reduce the production of reactive oxygen species. The species and content of mitoSC change in different tissues in aging and many mitochondria-related diseases. By summarizing the structure and function of mitoSC in different tissues of human and mammals, and the changes of mitoSC under conditions of aging, heart disease, type 2 diabetes, cancer and genetic defects, this review focuses on the effects of exercise on mitoSC and its related regulation mechanisms in order to offer an insight for exercise interventions in mitochondria-related diseases.
Animals ; Electron Transport ; Exercise ; Humans ; Mitochondria ; Mitochondrial Diseases ; Mitochondrial Membranes ; enzymology

We carried out a series of experiment demonstrating the role of mitochondria in the cytosolic and mitochondrial Ca2+ transients and compared the results with those from computer simulation. In rat ventricular myocytes, increasing the rate of stimulation (1~3 Hz) made both the diastolic and systolic [Ca2+] bigger in mitochondria as well as in cytosol. As L-type Ca2+ channel has key influence on the amplitude of Ca2+-induced Ca2+ release, the relation between stimulus frequency and the amplitude of Ca2+ transients was examined under the low density (1/10 of control) of L-type Ca2+ channel in model simulation, where the relation was reversed. In experiment, block of Ca2+ uniporter on mitochondrial inner membrane significantly reduced the amplitude of mitochondrial Ca2+ transients, while it failed to affect the cytosolic Ca2+ transients. In computer simulation, the amplitude of cytosolic Ca2+ transients was not affected by removal of Ca2+ uniporter. The application of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) known as a protonophore on mitochondrial membrane to rat ventricular myocytes gradually increased the diastolic [Ca2+] in cytosol and eventually abolished the Ca2+ transients, which was similarly reproduced in computer simulation. The model study suggests that the relative contribution of L-type Ca2+ channel to total transsarcolemmal Ca2+ flux could determine whether the cytosolic Ca2+ transients become bigger or smaller with higher stimulus frequency. The present study also suggests that cytosolic Ca2+ affects mitochondrial Ca2+ in a beat-to-beat manner, however, removal of Ca2+ influx mechanism into mitochondria does not affect the amplitude of cytosolic Ca2+ transients.
Animals ; Computer Simulation ; Cytosol ; Hydrazones ; Ion Transport ; Membranes ; Mitochondria ; Mitochondrial Membranes ; Muscle Cells ; Nitriles ; Rats

A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated. Cells with a higher MMP exhibited greater migration and invasion than those with a lower MMP. Cells that survived treatment with cisplatin, a standard chemotherapeutic drug for lung adenocarcinoma, exhibited increased MMP and enhanced migration and invasion compared with parental cells. Consistent with these findings, inhibition of mitochondrial activity significantly impeded the migration and invasion of cisplatin-resistant cells. RNA-sequencing analysis indicated that the expression of mitochondrial complex genes was upregulated in cisplatin-resistant cells. These results suggested that drug-resistant cells have a greater MMP and that inhibition of mitochondrial activity could be used to prevent metastasis of drug-resistant lung adenocarcinoma cells.
Adenocarcinoma* ; Cause of Death ; Cisplatin ; Humans ; Lung* ; Membrane Potential, Mitochondrial ; Metabolism ; Mitochondria ; Mitochondrial Membranes ; Neoplasm Metastasis ; Oxidative Phosphorylation ; Parents ; Prognosis

Ceramide induces cell death in a dose- and time-dependent manner in neuroblastoma SK-N-SH cells. To investigate the mechanism of SK-N-SH cell death by C2-ceramide, morphological features and Hoechst 33258 staining were analyzed. In these morphlogic study the cell death by ceramide showed typical apoptotic features, nuclear condensation, fragmentation, and membrane blebbing. Ceramide-induced apoptosis was accompanied by nuclear accumulation of p53. Inhibition of p53 expression with p53 antisense oligonucleotides inhibited apoptosis evoked by ceramide. Also, ceramide induced mitochondrial event, collapse of mitochondrial membrane potential (delta psi m) and interestingly, inhibition of p53 attenuated collapse of mitochondrial membrane potential, suggests that ceramide induces mitochondrial dysfunction through upregulation of p53 expression. These results suggest that ceramide-induced apoptosis is dependent upon increase in cellular p53 levels which play a critical role in the regulation of apoptotic cell death and p53 modulates mitochondrial function such as mitochondrial membrane potential level.
Apoptosis ; Bisbenzimidazole ; Blister ; Cell Death* ; Membrane Potential, Mitochondrial ; Membranes ; Neuroblastoma ; Neurons* ; Oligonucleotides, Antisense ; Up-Regulation

Amorphous silica particles, whose applications are increasing in many biomedical fields, are known to be less toxic than crystalline silica. In this study, the inflammatory effects of amorphous silica nanoparticles were investigated using 30-nm amorphous silica nanoparticles and human peripheral blood mononuclear cells (PBMCs) or purified monocytes. As a result, production of IL-1beta and IL-8 were increased. In addition, the mitochondrial reactive oxygen species (ROS) was detected, which may lead to mitochondrial membrane disruption. Most importantly, inflammasome formation was observed. Therefore, these results provide immunological information about amorphous silica nanoparticles and suggest that amorphous silica nanoparticles can evoke innate immune reactions in human monocytes through production of IL-1beta and IL-8.
Crystallins ; Humans ; Interleukin-8 ; Mitochondrial Membranes ; Monocytes ; Nanoparticles ; Reactive Oxygen Species ; Silicon Dioxide

Release of reactive oxygen species (ROS) generated in the mitochondria to the cytosol is well controlled by various proteins in order to maintain and regulate redox homeostasis and cellular signaling pathways, however, the exact mechanisms by which the proteins located in the mitochondrial membrane control ROS release still remains to be identified. Although there are reports that several proteins play a role in mitochondrial ROS release to the cytosol, little is known about how it is released into the cytosol or its origin. Recently, several reports demonstrated that the ROS modulator 1 (Romo1) protein located on the mitochondrial membrane modulates ROS release into the cytosol and that these ROS are indispensible for survival in both normal cells and tumor cells. If these ROS are over-produced or dysregulated in pathological conditions, they may cause oxidative damages resulting in a variety of diseases. Therefore, understanding and identifying the mechanisms by which ROS are released to the cytosol may offer new strategies for pharmaceutical therapy of diseases related to oxidative stresses.
Cytosol ; Homeostasis ; Mitochondria ; Mitochondrial Membranes ; Oxidation-Reduction ; Oxidative Stress ; Proteins ; Reactive Oxygen Species

Excessive use of alcohol is a serious problem in our society and induces various, severe alcohol related diseases. The cytotoxicities of ethanol are still largely unknown. We studied the molecular mechanisms of EtOH-induced SK-N-SH neuronal cell death and protective effects of baicalein and gramineus against EtOH-induced cytotoxicities. In our results, the cell death by EtOH showed morphologic features of apoptosis like as membrane blebbing, nuclear condensation and fragmentation. Furthermore, pretreated baicalein attenuated EtOH-induced neuronal cell death effectively. EtOH increased expression levels of p53 and both p53 antisense oligonucleotide and Pifithrin protected the cell death against EtOH. Also, EtOH induced mitochondrial event, collapse of mitochondrial membrane potential ( delta psi m ) and caspase cascade as a downstream of mitochondria. Interestingly, baicalein decreased expression levels of p53 and inhibited collapse of mitochondrial membrane potential. These results suggest that baicalein reduces mitochondrial dysfunction induced by EtOH through down-regulation of p53 expression levels. Also, baicalein attenuated activation of caspase, which was triggered by mitochondrial malfunction. But gramineus didn't have any protective effect. These results imply that baicalein significantly protects EtOH-induced neuronal cell death through regulating p53, mitochondrial dysfunction and caspase activation.
Apoptosis ; Blister ; Cell Death* ; Down-Regulation ; Ethanol ; Membrane Potential, Mitochondrial ; Membranes ; Mitochondria ; Neurons* ; Signal Transduction*

Excessive use of alcohol is a serious problem in our society and induces various, severe alcohol related diseases. The cytotoxicities of ethanol are still largely unknown. We studied the molecular mechanisms of EtOH-induced SK-N-SH neuronal cell death and protective effects of baicalein and gramineus against EtOH-induced cytotoxicities. In our results, the cell death by EtOH showed morphologic features of apoptosis like as membrane blebbing, nuclear condensation and fragmentation. Furthermore, pretreated baicalein attenuated EtOH-induced neuronal cell death effectively. EtOH increased expression levels of p53 and both p53 antisense oligonucleotide and Pifithrin protected the cell death against EtOH. Also, EtOH induced mitochondrial event, collapse of mitochondrial membrane potential ( delta psi m ) and caspase cascade as a downstream of mitochondria. Interestingly, baicalein decreased expression levels of p53 and inhibited collapse of mitochondrial membrane potential. These results suggest that baicalein reduces mitochondrial dysfunction induced by EtOH through down-regulation of p53 expression levels. Also, baicalein attenuated activation of caspase, which was triggered by mitochondrial malfunction. But gramineus didn't have any protective effect. These results imply that baicalein significantly protects EtOH-induced neuronal cell death through regulating p53, mitochondrial dysfunction and caspase activation.
Apoptosis ; Blister ; Cell Death* ; Down-Regulation ; Ethanol ; Membrane Potential, Mitochondrial ; Membranes ; Mitochondria ; Neurons* ; Signal Transduction*