• 대한임상검사과학회지
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• 제38권3호
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• pp.218-223
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• 2006

Sensorineural hearing loss is frequently found in patients with chronic renal failure (CRF). There have been many efforts to elucidate the etiologic factors of hearing loss in patients with CRF. However, there was not any clear identified cause of hearing loss. This study was undertaken to evaluate the activity of mitochondrial respiratory chain (MRC) in CRF patients with hearing impairment. To determine MRC activity, peripheral blood cells were obtained from CRF patients with hearing impairment receiving dialysis and normal subjects without any hearing problems. MRC activity of complex I and complex III was measured by the Trounces method. In MRC activities between the normal subjects group and CRF patients with hearing problems, the complex I and III activities of CRF patients with hearing problems were 63% and 85% compared with normal subjects (p<0.01). These results suggest that the activity of MRC may be implicated in the underlying mechanism of the hearing impairment in CRF patients, through mitochondrial DNA mutations at MRC complex I region with a decrement of MRC activity.

• Journal of Nutrition and Health
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• 제26권5호
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• pp.532-546
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• 1993

This study was done to investigate the effects of different dietary oils on hepatic mitochondrial lipid compositon, adenine nucleotide translocase(AdNT) and ATPase activities in carcinogen treated rats. Sixty male Sprague-Dawley rats, weighing 50∼60g, were fed three different types of dietary oil, beef tallow(BT), corn oil(CO) and sardine oil(SO) at 15% by weight for 14 weeks. Three weeks after feeding rats were intraperitoneally injected with a single dose of diethylnitrosamine(200mg/Kg BW). After five weeks rate fed 0.02% acetylaminofluorene contating diet for 6 weeks, and after seven weeks 0.05% phenobarbital containing diet for 7 weeks. At 14th week, rats were sacrificed and hepatic mitochondrial lipid composition, AdNT and ATPase activities were determined. Percent liver weight per body weight was significantly by carcinogen treatment. Analysis of mitochondrial lipid composition showed that body cholesterol and phospholipid contents were not affected by dietary oils but significantly increased by carcinogen treatment. Individual phospholipid composition as well as phosphatidyl ethanolamine/phosphatidyl choline ratio were altered by either dietary oils or carcinogen treatment. Fatty acid composition was changed by dietary oils but not much by carcinogen treatment. AdNT activity was affected by dietary oils in only carcinogen treated groups. ATPase activity was affected by dietary oils in only carcinogen nontreated groups. These data indicate that both dietary oils and caricinogen treatment can change mitochondrial lipid composition and thereby change AdNT and ATPase activities. Particularly effects of carcinogen treatment on cholesterol/phopholipid ratio, phospholipid compositon and ATPase activity were different among dietary oil groups. Therefore it is suggested that different dietary oils can somewhat modulate the changes of mitochnodrial lipid composition and membrane bound enzyme activites during hepatocarcinogenesis.

• BMB Reports
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• 제55권11호
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• pp.528-534
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• 2022

Mitochondria are cellular organelles that perform various functions within cells. They are responsible for ATP production, cell-signal regulation, autophagy, and cell apoptosis. Because the mitochondrial proteins that perform these functions need Ca²⁺ ions for their activity, mitochondria have ion channels to selectively uptake Ca²⁺ ions from the cytoplasm. The ion channel known to play the most important role in the Ca²⁺ uptake in mitochondria is the mitochondrial calcium uniporter (MCU) holo-complex located in the inner mitochondrial membrane (IMM). This ion channel complex exists in the form of a complex consisting of the pore-forming protein through which the Ca²⁺ ions are transported into the mitochondrial matrix, and the auxiliary protein involved in regulating the activity of the Ca²⁺ uptake by the MCU holo-complex. Studies of this MCU holo-complex have long been conducted, but we didn't know in detail how mitochondria uptake Ca²⁺ ions through this ion channel complex or how the activity of this ion channel complex is regulated. Recently, the protein structure of the MCU holo-complex was identified, enabling the mechanism of Ca²⁺ uptake and its regulation by the MCU holo-complex to be confirmed. In this review, I will introduce the mechanism of action of the MCU holo-complex at the molecular level based on the Cryo-EM structure of the MCU holo-complex to help understand how mitochondria uptake the necessary Ca²⁺ ions through the MCU holo-complex and how these Ca²⁺ uptake mechanisms are regulated.

• Molecules and Cells
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• 제46권6호
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• pp.374-386
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• 2023

Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pathways. Mitochondrial ribosomal protein (MRP) depletion enhanced the nucleolar granule formation of HSP70 and ubiquitin during HSR while facilitating the recovery of damaged nuclear proteins and impaired nucleocytoplasmic transport. Treatment of the mitochondrial proton gradient uncoupler masked MRP-depletion effects, implicating oxidative phosphorylation in these nuclear HSRs. On the other hand, MRP depletion and a reactive oxygen species (ROS) scavenger non-additively decreased mitochondrial ROS generation during HSR, thereby protecting the nuclear genome from DNA damage. These results suggest that suboptimal mitochondrial activity sustains nuclear homeostasis under cellular stress, providing plausible evidence for optimal endosymbiotic evolution via mitochondria-to-nuclear communication.

• Plant Biotechnology Reports
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• 제4권4호
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• pp.281-291
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• 2010

The rice CHLH gene encodes the $Mg^{2+}$-chelatase H subunit, which is involved in chlorophyll biosynthesis. Growth of the chlorophyll-deficient oschlh mutant is supported by mitochondrial activity. In this study, we investigated the activity of mitochondrial respiration in the illuminated leaves during oschlh seedling development. Growth of mutant plants was enhanced in the presence of 3% sucrose, which may be used by mitochondria to meet cellular energy requirements. ATP content in these mutants was, however, significantly lowered in light conditions. Low cytosolic levels of NADH in illuminated oschlh mutant leaves further indicated the inhibition of mitochondrial metabolism. This down-regulation was particularly evident for oxidative stressresponsive genes in the mutant under light conditions. Hydrogen peroxide levels were higher in oschlh mutant leaves than in wild-type leaves; this increase was largely caused by the impairment of the expression of the antioxidant genes, such as OsAPXl, OsRACl, and OsAOXc in knockout plants. Moreover, treatment of mesophyll protoplasts with ascorbic acid or catalase recovered ATP content in the mutants. Taken together, these results suggest that the light-mediated inhibition of mitochondrial activity leads to stunted growth of CHLH rice seedlings.

• Preventive Nutrition and Food Science
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• 제21권4호
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• pp.317-322
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• 2016

Mitochondrial biogenesis is a complex process requiring coordinated expression of nuclear and mitochondrial genomes. The peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-$1{\alpha}$) is a key regulator of mitochondrial biogenesis, and it controls mitochondrial DNA (mtDNA) replication within diverse tissues, including muscle tissue. The aim of this study was to investigate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mtDNA copy number and PGC-$1{\alpha}$ promoter activity in $C_2C_{12}$ muscle cells. mtDNA copy number and mRNA levels of genes related to mitochondrial biogenesis such as PGC-$1{\alpha}$, nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam) were assayed by quantitative real-time PCR. The PGC-$1{\alpha}$ promoter from -970 to +412 bp was subcloned into the pGL3-basic vector, which includes a luciferase reporter gene. Both EPA and DHA significantly increased mtDNA copy number, dose and time dependently, and up-regulated mRNA levels of PGC-$1{\alpha}$, NRF1, and Tfam. Furthermore, EPA and DHA stimulated PGC-$1{\alpha}$ promoter activity in a dose-dependent manner. These results suggest that EPA and DHA may modulate mitochondrial biogenesis, which was partially associated with increased mtDNA replication and PGC-$1{\alpha}$ gene expression in $C_2C_{12}$ muscle cells.

• The Korean Journal of Physiology and Pharmacology
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• 제9권5호
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• pp.299-304
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• 2005

Cardiac hypertrophy contributes an increased risk to major cerebrovascular events. However, the molecular mechanisms underlying cerebrovascular dysfunction during cardiac hypertrophy have not yet been characterized. In the present study, we examined the molecular mechanism of isoproterenol (ISO)-evoked activation of Ras/Raf/MAPK pathways as well as PKA activity in cerebral artery of rabbits, and we also studied whether the activations of these signaling pathways were altered in cerebral artery, during ISO-induced cardiac hypertrophy compared to heart itself. The results show that the mRNA level of c-fos (not c-jun and c-myc) in heart and these genes in cerebral artery were considerably increased during cardiac hypertrophy. These results that the PKA activity and activations of Ras/Raf/ERK cascade as well as c-fos expression in rabbit heart during cardiac hypertrophy were consistent with previous reports. Interestingly, however, we also showed a novel finding that the decreased PKA activity might have differential effects on Ras and Raf expression in cerebral artery during cardiac hypertrophy. In conclusion, there are differences in molecular mechanisms between heart and cerebral artery during cardiac hypertrophy when stimulated with β2 adrenoreceptor (AR), suggesting a possible mechanism underlying cerebrovascular dysfunction during cardiac hypertrophy.

• 한국균학회지
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• 제22권2호
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• pp.122-129
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• 1994

표고버섯의 mitochondria에 금속 chelating agent인 10 mM EDTA 및 10 mM o-Phe을 포함하는 10 mM Tris-HCl 완충용액(pH 7.5)으로 48시간 동안 각각 투석처리 하였을 때 mitochondria 내의 철 이온 함량이 투석처리를 하지 않은 대조구에 비하여 각각 74% 및 68% 감소되며, mitochondrial $F_1-ATPase$의 활성도는 대조구에 비하여 각각 56% 및 49%의 활성을 상실하였다. EDTA 투석에 의하여 활성을 상실한 metal-free mitochondrial $F_1-ATPase$는 $0.5\;mM\;Fe^{3+}$과 $0.05\;mM\;Mg^{2+}$에 의하여 각각 81% 및 70%의 활성이 회복되었으며, $Fe^{2+}$에 의해서는 활성이 회복되지 않았다. 또한 이 효소는 $0.5\;mM\;Fe^{3+}$와 $0.05\;mM\;Mg^{2+}$이 공존할 때 95%의 재활성화를 나타내었으며, $Fe^{2+}$와 $Mg^{2+}$의 공존 효과는 없었다. o-Phe으로 투석한 효소도 각 이온에 대하여 EDTA로 투석한 효소와 유사한 결과를 나타내었다. 그러므로, 표고버섯 내의 mitochondrial $F_1-ATPase$는 그 활성을 나타내는 데 있어서 $Fe^{3+}$ 및 $Mg^{2+}$을 필요로 함을 알았다. 기질 ATP에 대한 효소의 Km값은 1.67 mM이나, 효소를 가장 크게 활성화시키는 $0.5\;mM\;Fe^{3+}$와 $0.05\;mM\;Mg^{2+}$이 존재할 때의 Km값은 0.65 mM로서 기질 친화성이 증가되었다.

• Journal of Nutrition and Health
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• 제26권5호
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• pp.547-557
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• 1993

This study was done to investigate whether dietary fats differing in their fatty acid compositions change hepatic mitochondrial lipid composition and thereby change adenine nucleotide translocase activity. Male Sprague-Dawley rats were fed 5 different wxperimental diets for 6 weeks, which were different in their fatty acid compositions. The dietary fats were beef tallow(BT), olive oil(OO), corn oil(CO), perilla oil(PO) and sardine oil(SO) as a source of saturated fatty acid, oleic acid, n-6 linoleic acid, n-3 $\alpha$-linolenic acid and n-3 eiocosapentaenoic acid+docosahexaenoic acid respectively. Body weight of PO group was significantly higher than that of either BT or SO group. This increase in body weight of PO group was due to the increase of food intake. Although there was no difference in liver weight, % liver weight per body weight of SO group was significantly higher than BT and OO groups. Analysis of mitochondrial lipid composition showed that dietary oils differing their fatty acid compositions altered mitochondrial fatty acid patterns, especially n-6/n-3 ratio, cholesterol/phospholipid ratio and phopsholipid composition. The n-6/n-3 ratio was highest in CO group but lowest in SO group whereas the ratio of Chol/PL was highest in SO group but lowest in CO group. Such changes in mitochondrial lipids did not lead to a significant alteration in the activities of adenine nucleotide translocase, which is embedded in mitochodrial inner membrane.

• BMB Reports
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• 제55권9호
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• pp.459-464
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• 2022

Various mechanisms have been suggested to explain the chemopreventive and tumor-inhibitory effects of melatonin. Despite the growing evidence supporting melatonin-induced mitochondrial dysfunction, it remains largely unknown how this phenomenon modulates metabolic reprogramming in cancer cells. The aim of our study was to identify the mechanism underlying the anti-proliferative and apoptotic effects of melatonin, which is known to inhibit glycolysis. We analyzed the time-dependent effects of melatonin on mitochondrial respiration and glycolysis in liver cancer cells. The results showed that from a cell bioenergetic point of view, melatonin caused an acute reduction in mitochondrial respiration, however, increased reactive oxygen species production, thereby inhibiting mTORC1 activity from an early stage post-treatment without affecting glycolysis. Nevertheless, administration of melatonin for a longer time reduced expression of c-Myc protein, thereby suppressing glycolysis via downregulation of HK2 and LDHA. The data presented herein suggest that melatonin suppresses mitochondrial respiration and glycolysis simultaneously in HCC cells, leading to anti-cancer effects. Thus, melatonin can be used as an adjuvant agent for therapy of liver cancer.