• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.25-28
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• 2015

Mitochondrial disorders are rare metabolic diseases. They often present during neonatal period but with nonspecific clinical features such as feeding difficulties, failure to thrive, and seizures. Mitochondrial defects have also known to be associated with neurological disorders, as well as cancers. We report the first case of neonatal mitochondrial respiratory chain defect with sarcoma botryoides confirmed by pathologic diagnosis, suggesting another possible link between mitochondrial dysfunction and cancer.

• Korean Journal of Acupuncture
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• v.37 no.1
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• pp.37-45
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• 2020

Objectives : Mitochondria are typically known as intracellular double membrane-bound structures that supply energy for intracellular metabolism including Krebs cycle and beta-oxidation. Also, acupuncture has been known to stimulate the flow of energy. To explore the effect of acupuncture on the mitochondrial respiratory chain activities in rat's heart and kidneys, the activities of mitochondrial respiratory chain complexes I to IV were observed. Methods : The rats were divided into 11 groups; Normal (no acupuncture treatment and under anesthesia for 10 min), heart meridian five-transport-points (acupuncture treatment at HT9, HT8, HT7, HT4 and HT3 under anesthesia for 10 min), and kidney meridian five-transport-points (acupuncture treatment at KI1, KI2, KI3, KI7 and KI10 under anesthesia for 10 min). All rats were sacrificed and the heart and kidneys were examined for the changes of respiratory chain activities. Results : Acupuncture at HT7 increased the activity of succinate dehydrogenase; acupuncture at KI2 increased the activity of ubiquinol cytochrome C oxidoreductase; and acupuncture at HT9, HT8, HT3 and KI1 increased activities of cytochrome C oxidase. Conclusions : Acupuncture assists mitochondrial repiratory chain activity via the Cytochrome C oxidase signaling pathway in heart and kidney of rats.

• Journal of Life Science
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• v.26 no.10
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• pp.1137-1152
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• 2016

Cells sense, respond, and adapt to a low oxygen environment called hypoxia, which is widely involved in a variety of human diseases. Adaptation to low oxygen concentrations includes gene expression changes by inducing hypoxic genes and reducing aerobic genes. Recently, the mitochondrial respiratory chain has been implicated in the control of these oxygen-regulated genes when cells experience hypoxia. In order to obtain an insight into an effect of the mitochondrial respiratory chain on cellular response to hyxpoxia, we here examined whole genome transcript signatures of respiration-proficient and respiration-deficient budding yeasts exposed to hypoxia using DNA microarrays. By comparing whole transcriptomes to hypoxia in respiration-proficient and respiration-deficient yeasts, we found that there are several classes of oxygen-regulated genes. Some of them require the mitochondrial respiratory chain for their expression under hypoxia while others do not. We found that the majority of hypoxic genes and aerobic genes need the mitochondrial respiratory chain for their expression under hypoxia. However, we also found that there are some hypoxic and aerobic genes whose expression under hypoxia is independent of the mitochondrial respiratory chain. These results indicate a key involvement of the mitochondrial respiratory chain in oxygen-regulated gene expression and multiple mechanisms for controlling oxygen-regulated gene expression. In addition, we provided gene ontology analyses and computational promoter analyses for hypoxic genes identified in the study. Together with differentially regulated genes under hypoxia, these post-analysis data will be useful resources for understanding the biology of response to hypoxia.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.3
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• pp.95-98
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• 2018

A striking feature of mitochondrial disorders is the vast heterogeneity in their clinical symptoms that ranges from a single organ to severe multisystem involvement. Though a variety of ocular symptoms such as ptosis, pigmentary retinal degeneration, external ophthalmoplegia, and optic nerve atrophy can occur in association with mitochondrial cytopathies, progressive bilateral cataracts are rare among their ocular findings. A 5-year-old girl with no previous medical history came to our hospital presenting symptoms of seizure. She started showing progressive developmental regression, increased seizure frequency, hypotonia, general weakness, dysphagia and decreased vision. Lactic acidosis was noted in metabolic screening test and we confirmed mitochondrial respiratory chain complex I defect in spectrophotometric enzyme assay using the muscle tissue. Progressive bilateral cataracts then developed and were fully evident at the age of 7. She underwent cataract extraction with posterior chamber lens implantation. We are reporting a case of mitochondrial respiratory chain defect with multiorgan involvements including bilateral progressive cataract, an uncommon ocular manifestation. Ophthalmologic evaluation is highly recommended not to overlook the possible ocular manifestations in mitochondrial disorders.

• Korean Journal of Acupuncture
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• v.36 no.4
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• pp.200-209
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• 2019

Objectives : The liver is rich in mitochondria and it plays a key role in whole-body energy homeostasis. Mitochondria is double membrane-bound organelle that supplies energy for intracellular metabolism including Krebs cycle and beta-oxidation. Acupuncture is known to stimulate and regulate the flow of energy. To explore the effect of acupuncture on the mitochondrial respiratory chain activity in the rats' livers, the activity of mitochondrial respiratory chain complexes I to IV was observed. Methods : The rats were divided into 4 groups; Normal 1 (no acupuncture treatment and anesthesia for 5 min), Normal 2 (no acupuncture treatment and anesthesia for 10 min), MA1 (acupuncture treatment at bilateral LR3 under anesthesia for 5 min), and MA2 (acupuncture treatment at bilateral LR3 under anesthesia for 10 min). All rats were sacrificed and the livers were examined for respiratory chain change. Results : There was no difference in ubiquinon oxidoreductase, succinate dehydrogenase, and ubiquinol cytochrome C oxidoreductase after acupuncture at LR3. Acupuncture at LR3 for 10 min increased the activity of cytochrome C oxidase compared with no acupuncture groups. Conclusions : Acupuncture at LR3 mediated mitochondrial respiratory chain activity via the cytochrome C oxidase signaling pathway in the livers of rats.

• Clinical and Experimental Pediatrics
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• v.53 no.5
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• pp.644-647
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• 2010

Purpose: To evaluate myocardial conductivity to understand cardiac involvement in patients with mitochondrial disease. Methods: We performed retrospective study on fifty-seven nonspecific mitochondrial encephalopathy patients with no clinical cardiac manifestations. The patients were diagnosed with mitochondrial respiratory chain complex defects through biochemical enzyme assays of muscle tissue. We performed standard 12-lead electrocardiography (ECG) on all patients. Results: ECG abnormalities were observed in 30 patients (52.6%). Prolongation of the QTc interval (>440 ms) was seen in 19 patients (33.3%), widening of the corrected QRS interval in 15 (26.3%), and bundle branch block in four (7.0%). Atrioventricular block, premature atrial contraction and premature ventricular contraction were seen in two patients each (3.5%) and Wolff-Parkinson-White syndrome in one patient (1.8%). Conclusion: Given this finding, we recommend active screening with ECG in patients with mitochondrial disease even in patients without obvious cardiac manifestation.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.10 no.1
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• pp.1-25
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• 2010

• Molecules and Cells
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• v.40 no.4
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• pp.307-313
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• 2017

Caloric restriction (CR) has been shown to extend lifespan and prevent cellular senescence in various species ranging from yeast to humans. Many effects of CR may contribute to extend lifespan. Specifically, CR prevents oxidative damage from reactive oxygen species (ROS) by enhancing mitochondrial function. In this study, we characterized 33 single electron transport chain (ETC) gene-deletion strains to identify CR-induced chronological lifespan (CLS) extension mechanisms. Interestingly, defects in 17 of these 33 ETC gene-deleted strains showed loss of both respiratory function and CR-induced CLS extension. On the contrary, the other 16 respiration-capable mutants showed increased CLS upon CR along with increased mitochondrial membrane potential (MMP) and intracellular adenosine triphosphate (ATP) levels, with decreased mitochondrial superoxide generation. We measured the same parameters in the 17 non-respiratory mutants upon CR. CR simultaneously increased MMP and mitochondrial superoxide generation without altering intracellular ATP levels. In conclusion, respiration is essential for CLS extension by CR and is important for balancing MMP, ROS, and ATP levels.

• Journal of Life Science
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• v.9 no.1
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• pp.1-4
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• 1999

Large-scale deletions of mitochondrial DNA(mtDNA) have been documented in patients with mitochondrial myopathies and seem to be especially frequent in patients with Kearns-Sayre syndrome (KSS). About one third of all patients shows a 4,977 bp deletion, known as the "common deletion", that removes a segment of DNA that includes several genes encoding for respiratory chain subunits. In this disorder, the population of deleted mtDNA molecules coexists with population of normal, wild-type full length mtDNAs, a situation known as heteroplasmy. We have performed polymerase chain reaction (PCR) on paraffin-embedded muscle tissues from two korean KSS patients. The PCR analysis revealed the existence of two amplified fragments, the deleted fragments, the deleted fragment of 123 bp characteristic for common deletion and the wild-type fragment of 152 bp.of 152 bp.

• BMB Reports
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• v.44 no.5
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• pp.298-305
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• 2011

Most intracellular reactive oxygen species (ROS), especially superoxide anion ($O_2^{{\bullet}_-}$) that is converted from oxygen, are overproduced by excessive electron leakage from the mitochondrial respiratory chain. Intracellular oxidative stress that damages cellular components can contribute to lifestyle-related diseases such as diabetes and arteriosclerosis, and age-related diseases such as cancer and neuronal degenerative diseases. We have previously demonstrated that the excessive mitochondrial $O_2^{{\bullet}_-}$ production caused by SDHC mutations (G71E in C. elegans, I71E in Drosophila and V69E in mouse) results in premature death in C. elegans and Drosophila, cancer in mouse embryonic fibroblast cells and infertility in transgenic mice. SDHC is a subunit of mitochondrial complex II. In humans, it has been reported that mutations in SDHB, SDHC or SDHD often result in inherited head and neck paragangliomas (PGLs). Recently, we established Tet-mev-1 conditional transgenic mice using our uniquely developed Tet-On/Off system, which equilibrates transgene expression to endogenous levels. These mice experienced mitochondrial respiratory chain dysfunction that resulted in $O_2^{{\bullet}_-}$ overproduction. The mitochondrial oxidative stress caused excessive apoptosis leading to low birth weight and growth retardation in the neonatal developmental phase in Tet-mev-1 mice. Here, we briefly describe the relationships between mitochondrial $O_2^{{\bullet}_-}$ and aging phenomena in mev-1 animal models