• Archives of Pharmacal Research
• /
• v.26 no.11
• /
• pp.951-959
• /
• 2003

A series of typical (chlorpromazine, haloperidol and thioridazine) and atypical (risperidone, quetiapine, clozapine and olanzapine) antipsychotics were tested for effects on integrated bioenergetic functions of isolated rat liver mitochondria. Polarographic measurement of oxygen consumption in freshly isolated mitochondria showed that electron transfer activity at respiratory complex I is inhibited by chlorpromazine, haloperidol, risperidone, and quetiapine, but not by clozapine, olanzapine, or thioridazine. Chlorpromazine and thioridazine act as modest uncouplers of oxidative phosphorylation. The typical neuroleptics inhibited NADH-coenzyme Q reductase in freeze-thawed mitochondria, which is a direct measure of complex I enzyme activity. The inhibition of NADH-coenzyme Q reductase activity by the atypicals risperidone and quetiapine was 2-4 fold less than that for the typical neuroleptics. Clozapine and olanzapine had only slight effects on NADH-coenzyme Q reductase activity, even at 200 $\mu$ M. The relative potencies of these neuroleptic drugs as inhibitors of mitochondrial bioenergetic function is similar to their relative potencies as risk factors in the reported incidence of extrapyramidal symptoms, including tardive dyskinesia (TD). This suggests that compromised bioenergetic function may be involved in the cellular pathology underlying TD.

• Reproductive and Developmental Biology
• /
• v.35 no.4
• /
• pp.427-434
• /
• 2011

Mitochondria diseases have been reported to involve structural and functional defects of complex I-V. Especially, many of these diseases are known to be related to dysfunction of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I). The dysfunction of mitochondria complex I is associated with neurodegenerative disorders, such as Parkinson's disease, Huntington's disease, and Leber's hereditary optic neuropathy (LHON). Mammalian mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) is largest and consists of at least 46 different subunits. In contrast, the NDI1 gene of Saccharomyces cerevisiae is a single subunit rotenone-insensitive NADH-quinone oxidoreductase that is located on the matrix side of the inner mitochondrial membrane. The Saccharomyces cerevisiae NDI1 gene using a recombinant adeno-associated virus vector (rAAV-NDI1) was successfully expressed in AML12 mouse liver hepatocytes and the NDI1-transduced cells were able to grow in media containing rotenone. In contrast, control cells that did not receive the NDI1 gene failed to survive. The expressed Ndi1 enzyme was recognized to be localized in mitochondria by confocal immunofluorescence microscopic analyses and immunoblotting. Using digitonin-permeabilized cells, it was shown that the NADH oxidase activity of the NDI1-transduced cells was not affected by rotenone which is inhibitor of complex I, but was inhibited by antimycin A. Furthermore, these results indicate that Ndi1 can be functionally expressed in the AML12 mouse liver hepatocytes. It is conceivable that the NDI1 gene is powerful tool for gene therapy of mitochondrial diseases caused by complex I deficiency. In the future, we will attempt to functionally express the NDI1 gene in mouse embryonic stem (mES) cell.

• Applied Microscopy
• /
• v.28 no.2
• /
• pp.159-170
• /
• 1998

The glandular secretory system of the capitate gandular trichomes in leaf of Thymus quinquecostatus Celakovsky was examined by transmission electron microscope. The glandular trichome was consisted of three cell layers; an basal cell layer, a stalk cell with single-celled intermediate layer and a discoid secretory layer with thickened cuticle. The secretory cell was dense, rich in mitochondria, rER, plastds, Golgi complex and had many vesicular structure. Typical plastids with reticulate body and plastoglobule were present in glandular trichome. The tytoplasm of secretory cell was filled with osmiophilic secretory materials. The secretory vesicles, originated from Golgi complex, appeared as membrane bounded vesicles and secreted to the outer wall surface. The presences of well developed rER, mitochondria, Golgi complex, and membrane-bounded vesicles fused with plasmalemma in the secreting cells indicate that the granulocrine mechanism of secretion was occurring in T. quinquecostatus. Subcuticular cavity was developed between the cuticular layer and the secretory cell wall, and it formed above the secretory cell upon separation of cuticle-wall.

• Applied Microscopy
• /
• v.24 no.4
• /
• pp.41-51
• /
• 1994

The topology of the enzyme has been investigated by biochemical studies including chemical labeling and cross linking. Thirteen subunits(polypeptides) of the cytochrome-c-oxidase have localistic characteristics of existing in the matrix side or cytoplasmic side in the mitochondria. In order to observe the distribution of the enzyme subunit on the mitochondria membrane, immunogold-labeling methods were employed. Antibody was obtained from the serum of immunized rabbit with enzyme subunit antigen which was obtained from cytochrome-c-oxidase of the beef heart muscle mitochondria. Beef heart muscle tissue as a tissue antigen was stained with immunized rabbit IgG and protein A gold complex. Electron microscopy has identified the existance of cytochrome-c-oxidase subunit $Mt_I,\;Mt_{II}\;and\;Mt_{III}$ on the membrane of cristae and outer chamber of mitochondria and the subunit $C_{IV}$ on the membrane of cristae and matrix of mitochondria. Particularly, the subunit $C_{IV}$ was also observed to exist in the sarcoplasm of muscle tissue.

• Molecules and Cells
• /
• v.23 no.3
• /
• pp.363-369
• /
• 2007

Mitochondria play a central role in energy-generating processes and may be involved in the regulation of channels and receptors. Here we investigated TRPM7, an ion channel and functional kinase, and its regulation by mitochondria. Proton ionophores such as CCCP elicited a rapid decrease in outward TRPM7 whole-cell currents but a slight increase in inward currents with pipette solutions containing no MgATP. With pipette solutions containing 3 mM MgATP, however, CCCP increased both outward and inward TRPM7 currents. This effect was reproducible and fully reversible, and repeated application of CCCP yielded similar decreases in current amplitude. Oligomycin, an inhibitor of $F_1/F_O$-ATP synthase, inhibited outward whole-cell currents but did not affect inward currents. The respiratory chain complex I inhibitor, rotenone, and complex III inhibitor, antimycin A, were without effect as were kaempferol, an activator of the mitochondrial $Ca^{2+}$ uniporter, and ruthenium red, an inhibitor of the mitochondrial $Ca^{2+}$ uniporter. These results suggest that the inner membrane potential (as regulated by proton ionophores) and the $F_1/F_O$-ATP synthase of mitochondria are important in regulating TRPM7 channels.

• Korean Journal of Ichthyology
• /
• v.19 no.4
• /
• pp.286-291
• /
• 2007

The bitterling, Acheilognathus koreensis spermatozoon has been examined by electron microscopy. The epididymal spermatozoa of A. koreensis are representing typical characteristic of cyprinid spermatozoa including the lateral insertion of flagellum, the organization of centriolar complex in shallow nuclear fossa and the asymmetrical arrangement of mitochondria. The sperm mid-piece contains a large mitochondrion characteristic enclosed by membranous vesicles. The mitochondria aspect is different from that of other cyprinid spermatozoa, which their mitochondria have a conventional aspect and never fuse to form a mitochondrial derivative. In term of sperm evolution, the fused mitochondria are regarded as the apomorphic character in comparison with the separate mitochondria. The single mitochondrion is not found in cyprinid spermatozoon except for Rodeus and Pungtungia.

• Development and Reproduction
• /
• v.22 no.3
• /
• pp.213-223
• /
• 2018

Ultrastructural studies on oocyte differentiation and vitellogenesis in the oocytes of female Kareius bicoloratus were investigated by transmission electron microscopy. The Golgi complex in the cytoplasm is involved in the formation of yolk vesicles that contain yolk carbohydrates in the yolk vesicle of oocytes in the early vitellogenic phase. In this phase, many pinocytotic vesicles (PVs), which are formed by pinocytosis, contain yolk precursors (exogenous substances). These substances are associated with exogenous heterosynthetic vitellogenesis. In yolked oocytes in the late vitellogenic phase, two morphologically different bodies, which formed by modified mitochondria, appear in oocytes. One is a multivesicular body (synthesized by autosynthetic vitellogenesis), and the other is a yolk precursor (an exogenous substance formed by heterosynthetic vitellogenesis). The multivesicular bodies (MVB) are taken into the yolk precursors (YP) and are transformed into primary yolk globules. However, after the YP mix with exogenous PVs near the zona pellucida, they are transformed into primary yolk globules. Vitellogenesis of this species occurs via endogenous autosynthesis and exogenous heterogenesis. Vitellogenesis occurs through endogenous autosynthesis, which involves the combined activity of the Golgi complex, mitochondria and MVB formed by modified mitochondria. However, heterosynthesis involves pinocytotic incorporation of extraovarian precursors (such as vitellogenin in the liver) into the zona pellucida (via granulosa cells and thecal cells) of the yolked oocyte.

• Journal of Life Science
• /
• v.28 no.12
• /
• pp.1397-1405
• /
• 2018

Mitochondria have multiple functions in cells: providing chemical energy, storing cellular $Ca^{2+}$, generating reactive oxygen species, and regulating apoptosis. Through these functions, mitochondria are also involved in the maintenance, proliferation, and differentiation of stem/progenitor cells. In the brain, the subventricular zone (SVZ) is one of the neurogenic regions that contains neural stem cells (NSCs) throughout a lifetime. However, reports on the role of mitochondria in SVZ NSCs are scarce. Here, we show that rotenone, a complex I inhibitor of mitochondria, inhibits the proliferation and differentiation of SVZ NSCs in different ways. In proliferating NSCs, rotenone decreases mitosis as measured through phosphorylated histone H3 detection; moreover, apoptosis is not induced by rotenone at 50 nM. In differentiating NSCs, rotenone blocks neurogenesis and oligodendrogenesis while glial fibrillary acidic protein-positive astrocytes are not affected. Interestingly, in this study there were more cells in the differentiating NSCs treated with rotenone for 4-6 days than in the vehicle control group which was a different effect from the reduced number of cells in the proliferating NSCs. We examined both apoptosis and mitosis and found that rotenone decreased apoptosis as detected by staining cleaved caspase-3 but did not affect mitosis. Our results suggest that functional mitochondria are necessary in both the proliferation and differentiation of SVZ NSCs. Furthermore, mitochondria might be involved in the mitosis and apoptosis that occur during those processes.

• Microbiology and Biotechnology Letters
• /
• v.5 no.4
• /
• pp.185-189
• /
• 1977

After administering overdosage of vitamin A, D ＆ E to the matured female chicken, the changes of the epithelial cells of the proximal convoluted tubule were observed and the results were summarized at follows. In the group treated with 2.5 ml of Rovisol, the mitochondria were slightly swollen and free ribosomes were mildly increased. The mitochondria were more swollen, microvilli were somewhat irregular and fused chondriosphere were noted when the chicken were treated with 7.5 ml of Rovisol. When the thicken were treated with 12.5ml of Rovisol the cell sap was markedly edematous so that the cellular organelles seemed to reduce. Also noted were chondriospgere and increased free ribosomes. According to the results of this study it is considered that the changes of the epithelial cells of proximal convoluted tubules of tile matured hens after administering overdosage of vitamin complex are mainly cellular swelling and are reversible ones.

• Development and Reproduction
• /
• v.7 no.2
• /
• pp.89-93
• /
• 2003

The present study observed the ultrastructure of testis of bluespotted mud hopper(Boleophthalmus pectinirostris), and sperrnatogenesis was discussed also. The testis was surrounded by a thin adventitia, inside which spermatocyst composed the parenchyma of testis. Each lobule was enwrapped by many spermatocysts, which were filled with different kinds of spermatogenic cell clusters at the same developmental stage. In the lobule lumen there are large numbers of spermatozoa The thin adventitia(outer wall) of testis was composed of outer epithelium, and the underlying layers, such as collagen fiber layer, and myoid tissue. The myoid tissue elongated into the inside of testis, became the main componentof interstitium between spermatocyst where sperrnatogenesis occurred. In addition interstitial cells containing dense homogeneous nucleus and abundant mitochondria were observed. Spermatogonia contained round nucleus with diffuse chromatin and nucleolus, and dense nuclear bodies surround by mitochondria in cytoplasm. The synaptonemal . complex was observed in primary spermatocytes clearly. Early spermatid presented larger round nucleus composed of granular chromatin, which was located in the center of cytoplasm. The nucleus of mid-spermatid composed of finely granular chromatin lied on one side of spermatid, and abundant mitochondria had migrated another side. A nuclear fossa appeared in the site near mitochondria in late-spermatid, and the centriole was formed in nuclear fossa.