• Korean Journal of Veterinary Research
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• v.36 no.3
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• pp.565-570
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• 1996

Cardiac, hepatic and renal mitochondria in rats fed lead containing diets were isolated and their activities were studied in terms of NADH oxidation. In normal rats, cardiac and renal mitochondria had similar activities and showed activity values of higher than those in hepatic mitochondria. Cardiac mitochondiral activities in rats fed lead containing diets were increased after 4 weeks of feeding but decreased to activity values close to normal. Renal mitochondrial activities showed a trend of inhibition in all groups fed lead containing diets but were no differenes by feeding periods of 4 and 8 weeks. Feeding of lead containing diets could not be attributed to any changes in the hepatic mitochondrial antivities at experimental doses during 4~8 weeks.

• Applied Microscopy
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• v.26 no.3
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• pp.315-328
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• 1996

This study aims to demonstrate the effect of SOD (superoxide dismutase), one of the antioxidant enzymes, on the ultrastructural changes in the parietal cells caused by the administration of cisplatin in the rat. A total of 60 healthy Sprague-Dawley rats weighing about 200 gm were used as experimental animals. Cisplatin (6 mg/kg) was administered intraperitoneally to rats pretreated with 15,000 unit/kg of SOD or rats without the pretreatment. The experimental animals were sacrificed at 6 hours, 12 hours, 24 hours and 3 days after the administration of cisplatin. The results were as follows: 1. SOD alone did not affect the ultrastructural changes in the gastric parietal cells in the rat. 2. Irregular shaped mitochondria, mitochondria with dim cristae, dilated cristae, ruptured outer membrane, electron lucent matrix and degenerative mitochondria were seen in cisplatin treated rat. Whorled membranous body, many lysosomes and large vacuole were observed in the gastric parietal cells in cisplatin treated rat. 3. Mitochondria with dilated cristae and electron lucent matrix and irregular shaped mitochondria were observed in the gastric parietal cells of the cisplatin treated rat with pretreatment of SOD. These results suggest that SOD attenuates the toxic effect of the cisplatin in the gastric parietal cells of the rat.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.89-102
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• 1982

The $Na^+-and\;K^+-induced\;Ca^{++}$ release was measured isotopically by millipore filter technique in pig heart mitochondria. With EGTA-quenching technique, the characteristics of mitochondrial $Ca^{++}-pool$ and the sources of $Ca^{++}$ released from mitochondria by $Na^+\;or\;K^+$ were analyzed. The mitochondrial $Ca^{++}-pool$ could be distinctly divided into two components: internal and external ones which were represented either by uptake through inner membrane, or by energy independent passive binding to external surface of mitochondria, respectively. In energized mitochondria, a large portion of $Ca^{++}$was transported into internal pool with little external binding, while in de-enerigzed state, a large portion of transported $Ca^{++}$ existed in the external pool with limited amount of $Ca^{++}$ in the internal pool which was possibly transported through the $Ca^{++}-carrier$ present in the inner membrane. $Na^+$ induced the $Ca^{++}$ release from both internal pool and external pool and external binding pool of mitochondria. In contrast, $K^+$ did not affect $Ca^{++}$ of the internal pool, but, displaced $Ca^{++}$ bound to external surface of the mitochondria. When the $Ca^{++}-reuptake$ was blocked by EGTA, the $Ca^{++}$ release from the internal pool by $Na^+$ was rapid; the rate of $Ca^{++}-efflux$ appeared to be a function of $[Na^+]^2$ and about 8mM $Na^+$ was required to elicit half-maximal velocity of $Ca^{++}-efflux$. So it was revealed that $Ca^{++}-efflux$ velocity was particulary sensitive to small changes of the $Na^+$ concentration in physiological range. Energy independent $Ca^{++}-binding$ sites of mitochondrial external surface showed unique characteristics. The total number of external $Ca^{++}-binding$ sites of pig heart mitochondria was 29 nmoles per mg protein and the dissociation constant(Kd) was $34{\mu}M$. The $Ca^{++}-binding$ to the external sites seemed to be competitively inhibited by $Na^+\;and\;K^+$; the inhibition constant(Ki) were 9.7 mM and 7.1 mM respectively. Considering the intracellular ion concentrations and large proportion of $Ca^{++}$ uptake in energized mitochondria, the external $Ca^{++}-binding$ pool of the mitochondria did not seem to play a significant role on the regulation of intracellular free $Ca^{++}$ concentration. From this experiment, it was suggested that a small change of intracellular free $Na^+$ concentration might play a role on regulation of free $Ca^{++}$ concentration in cardiac cell by influencing $Ca^{++}-efflux$ from the internal pool of mitochondria.

• The Korean Journal of Pharmacology
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• v.8 no.1
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• pp.67-75
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• 1972

Many studies on the mechanism of the inotropic action of cardiac glycosides have shown the possible intimate relationship between the mobilization of intracellular calcium and inotropic effect. Evidence obtained from recent studies suggests that cardiac glycosides may increase the intracellular $Ca^{++}$ concentration through the release of this ion from cellular or intracellular membrane. It seemed imperative to study the effect of ouabain on the interaction between mitochondria and $Ca^{++}$, because mitochondria are known to have a rather powerful $Ca^{++}$ pump mechanism which may have an important role on the regulation of intracellular $Ca^{++}$ concentration. The present investigations was made into the effect of ouabain on $Ca^{++}$ untake of mitochondria in the presence of ATP and its dependence on $K^+$ and $Na^+$ in the medium. The results are summarized as follows: 1. The rate of rise in the turbidity of superprecipitation was solely influenced by ionic strength of the medium, not by the species of ion, i.e. $Na^+$ or $K^+$. The higher ionic strength suppressed and the lower enhanced the rate of superprecipitation respectively. 2. No effect of ouabain was found on the rate of superprecipitation. 3. Mitochondria depressed the rate of superpretipitation, and the depressed rate of superprecipitation by mitochondria was reversed by ouabain, and the degree of this reversal was almost identical in $Na^+$ and $K^+$ medium. 4. $Ca^{++}$ uptake of mitochondria was inhibited by ouabain in the presence of ATP and the degree of inhibition showed the dose-response manner in terms of concentration of ouabain. 5. In the absence of ATP, mitochondria took or the $Ca^{++}$ in initial period but released it later. Such uptake and release of $Ca^{++}$ was not influenced by ouabain. 6. It is suggested that intracellular calcium mobilization by ouabain through the action upon the mitochondria was due to inhibition on ATP-dependent $Ca^{++}$ uptake by this agent, not to the action upon so called binding.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1283-1288
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• 2000

Objectives : The subcellular locations of Bad, Bid, Bax and Bcl-XL change during apoptosis and this change is important for the regulation of cell death. The purpose this study was to elucidate binding of Bad with Bcl-XL in vivo Methods : We mads Bad with Green Fluorescent Protein(GFP) using PCR method. We transfected and overexpressed GFP-Bad with or without Bcl-XL cotransfection in living COS-7 cell. Results : Bad and Bcl- XL bind one another in healthy living cells and this association controled mitochondrial docking. In the absence of Bad-XL, Bad was mainly cytosolic and partially bound to mitochondria. Upon coexpression of Bad and Bcl-XL, most of Bad translocated to mitochondria. These should suggest that Bad binds to the mitochondrial and cytoplasmic forms of Bcl-XL and Bad bound to cytoplasmic Bcl-XL translocates to mitochondria. These in vivo findings confirm that Bad make a complexes with Bcl- XL and cause mitochondrial translocation of Bad-Bcl-XL complex.

• Molecules and Cells
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• v.44 no.9
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• pp.637-646
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• 2021

Free fatty acids are converted to acyl-CoA by long-chain acyl-CoA synthetases (ACSLs) before entering into metabolic pathways for lipid biosynthesis or degradation. ACSL family members have highly conserved amino acid sequences except for their N-terminal regions. Several reports have shown that ACSL1, among the ACSLs, is located in mitochondria and mainly leads fatty acids to the β-oxidation pathway in various cell types. In this study, we investigated how ACSL1 was localized in mitochondria and whether ACSL1 overexpression affected fatty acid oxidation (FAO) rates in C2C12 myotubes. We generated an ACSL1 mutant in which the N-terminal 100 amino acids were deleted and compared its localization and function with those of the ACSL1 wild type. We found that ACSL1 adjoined the outer membrane of mitochondria through interaction of its N-terminal region with carnitine palmitoyltransferase-1b (CPT1b) in C2C12 myotubes. In addition, overexpressed ACSL1, but not the ACSL1 mutant, increased FAO, and ameliorated palmitate-induced insulin resistance in C2C12 myotubes. These results suggested that targeting of ACSL1 to mitochondria is essential in increasing FAO in myotubes, which can reduce insulin resistance in obesity and related metabolic disorders.

• BMB Reports
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• v.38 no.5
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• pp.619-623
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• 2005

The efficacy of chemotherapeutic agents on tumor cells has been shown to be modulated by tumor suppressor gene p53 and its target genes such as Bcl-2 family members (Bax, Noxa, and PUMA). However, various chemotherapeutic agents can induce cell death in tumor cells that do not express the functional p53, suggesting that some chemotherapeutic agents may induce cell death in a p53-independent pathway. Here we showed that etoposide can induce the similar degree of cell death in p53-deficient HCT 116 cells, whereas 5'-FU-mediated cell death is strongly dependent on the existence of functional p53 in HCT 116 cells. Further, we provide the evidence that etoposide can induce the cytochrome c release from isolated mitochondria, and etoposide-induced cytochrome c release is not accompanied with the large amplitude swelling of mitochondria. These data suggest that etoposide can directly induce the mitochondrial dysfunction irrespective of p53 status, and it may, at least in part, account for the p53-independent pathway in cell death induced by chemotherapeutic agents.

• BMB Reports
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• v.48 no.10
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• pp.541-548
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• 2015

Cardiomyopathy is an inherited or acquired disease of the myocardium, which can result in severe ventricular dysfunction. Mitochondrial dysfunction is involved in the pathological process of cardiomyopathy. Many dysfunctions in cardiac mitochondria are consequences of mutations in nuclear or mitochondrial DNA followed by alterations in transcriptional regulation, mitochondrial protein function, and mitochondrial dynamics and energetics, presenting with associated multisystem mitochondrial disorders. To ensure correct diagnosis and optimal management of mitochondrial dysfunction in cardiomyopathy caused by multiple pathogenesis, multidisciplinary approaches are required, and to integrate between clinical and basic sciences, ideal translational models are needed. In this review, we will focus on experimental models to provide insights into basic mitochondrial physiology and detailed underlying mechanisms of cardiomyopathy and current mitochondria-targeted therapies for cardiomyopathy.

• BMB Reports
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• v.52 no.12
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• pp.679-688
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• 2019

The decrease of metabolism in the brain has been observed as the important lesions of Alzheimer's disease (AD) from the early stages of diagnosis. The cumulative evidence has reported that the failure of mitochondria, an organelle involved in diverse biological processes as well as energy production, maybe the cause or effect of the pathogenesis of AD. Both amyloid and tau pathologies have an impact upon mitochondria through physical interaction or indirect signaling pathways, resulting in the disruption of mitochondrial function and dynamics which can trigger AD. In addition, mitochondria are involved in different biological processes depending on the specific functions of each cell type in the brain. Thus, it is necessary to understand mitochondrial dysfunction as part of the pathological phenotypes of AD according to each cell type. In this review, we summarize that 1) the effects of AD pathology inducing mitochondrial dysfunction and 2) the contribution of mitochondrial dysfunction in each cell type to AD pathogenesis.

• Molecules and Cells
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• v.43 no.1
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• pp.10-22
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• 2020

Mitochondria have several quality control mechanisms by which they maintain cellular homeostasis and ensure that the molecular machinery is protected from stress. Mitophagy, selective autophagy of mitochondria, promotes mitochondrial quality control by inducing clearance of damaged mitochondria via the autophagic machinery. Accumulating evidence suggests that mitophagy is modulated by various microbial components in an attempt to affect the innate immune response to infection. In addition, mitophagy plays a key role in the regulation of inflammatory signaling, and mitochondrial danger signals such as mitochondrial DNA translocated into the cytosol can lead to exaggerated inflammatory responses. In this review, we present current knowledge on the functional aspects of mitophagy and its crosstalk with innate immune signaling during infection. A deeper understanding of the role of mitophagy could facilitate the development of more effective therapeutic strategies against various infections.