• Journal of Korean Medicine for Obesity Research
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• v.14 no.2
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• pp.55-62
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• 2014

Objective: The prevalence of metabolic syndrome and type 2 diabetes is increasing worldwide. Mitochondrial dysfunction is known to be involved in insulin resistance and obesity, researches have been increasing highly. Astragali Radix extract (ARE) or its main components have been shown to perform comparably to insulin by significantly reducing blood glucose levels in animal models however, the influence on mitochondrial dysfunction are not well understood. Methods: ARE (0.2, 0.5 and 1.0 mg/ml) or metformin (2.5 mM) were treated in C2C12 after 6 day-differentiation. The expressions of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and phosphorylation AMPK, peroxisome proliferators-activated receptror ${\gamma}$ coactivator $1{\alpha}$ ($PGC1{\alpha}$), nuclear respiratory factors 1 (NRF1), mitochondrial transcription factor (Tfam) and myosin heavy chain were detected with western blotting or polymerase chain reaction analysis. The morphological changes were also investigated. Results: ARE dose dependently increased phosphorylation of AMPK and respectively activated mRNA expressions of $PGC1{\alpha}$, NRF1 and Tfam which are mitochondrial biogenesis regulators. Furthermore, there were some morphologic differences of differentiated cells between ARE treatment and control. Conclusions: This study suggests that ARE has the potential to increase muscle mitochondrial function by activating AMPK and $PGC1{\alpha}$.

• Clinical and Experimental Pediatrics
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• v.52 no.4
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• pp.471-475
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• 2009

Purpose : Mitochondrial disorders are a clinical entity characterized by diverse symptoms and signs of involvement of various systems. Furthermore, the disorders are known to show ophthalmologic manifestations as well as neurological findings. Visually evoked potential is a sensitive measure to check the integrity of the visual pathway. In this study, we have investigated the value of visually evoked potential in mitochondrial disorders with respiratory chain defects. Methods : Nineteen patients diagnosed with mitochondrial respiratory chain complex I defect as confirmed by spectrophotometric enzyme assay in muscle samples were enrolled for this study. The patients underwent a visually evoked potential study. We classified the results into four groups and compared these with clinical ophthalmologic findings. Results : Among the 19 patients, 14 showed abnormal visually evoked potential findings. Seven patients showed abnormal clinical ophthalmologic findings. All patients with abnormal ophthalmologic findings showed abnormal visually evoked potential findings. Among the 12 patients with normal ophthalmologic findings, seven showed abnormal results in visually evoked potential. Conclusion : Visually evoked potential study could be used as an effective screening tool for mitochondrial disorders to detect ophthalmologic and neurological abnormalities.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.750-758
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• 2022

Background: Mild cognitive impairment (MCI) is a transitional condition between normality and dementia. Ginseng is known to have effects on attenuating cognitive deficits in neurogenerative diseases. Ginsenosides are the main bioactive component of ginseng, and their protein targets have not been fully understood. Furthermore, no thorough analysis is reported in ginsenoside-related protein targets in MCI. Methods: The candidate protein targets of ginsenosides in brain tissues were identified by drug affinity responsive target stability (DARTS) coupled with label-free liquid chromatography-mass spectrometry (LC-MS) analysis. Network pharmacology approach was used to collect the therapeutic targets for MCI. Based on the above-mentioned overlapping targets, we built up a proteineprotein interaction (PPI) network in STRING database and conducted gene ontology (GO) enrichment analysis. Finally, we assessed the effects of ginseng total saponins (GTS) and different ginsenosides on mitochondrial function by measuring the activity of the mitochondrial respiratory chain complex and performing molecular docking. Results: We screened 2526 MCI-related protein targets by databases and 349 ginsenoside-related protein targets by DARTS. On the basis of these 81 overlapping genes, enrichment analysis showed the mitochondria played an important role in GTS-mediated MCI pharmacological process. Mitochondrial function analysis showed GTS, protopanaxatriol (PPT), and Rd increased the activities of complex I in a dose-dependent manner. Molecular docking also predicted the docking pockets between PPT or Rd and mitochondrial respiratory chain complex I. Conclusion: This study indicated that ginsenosides might alleviate MCI by targeting respiratory chain complex I and regulating mitochondrial function, supporting ginseng's therapeutic application in cognitive deficits.

• Applied Microscopy
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• v.48 no.4
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• pp.81-86
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• 2018

The respiratory chain complex forms a supercomplex (SC) in the inner mitochondrial membrane. This complex facilitates the process of electron transfer to produce the proton gradient used to synthesize ATP. Understanding the precise structure of the SC is considered an important challenge. However, it has not yet been reported. The development of a Cryo-electron microscopy (EM) technique provides an effective way to obtain high-resolution micrographs to determine the high-resolution three-dimensional structure of biomolecules. In this brief review, the currently reported Cryo-EM structures of the mammalian respirasome have been described in order to establish a direction for further research in the respiratory system.

• Clinical and Experimental Pediatrics
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• v.53 no.12
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• pp.994-999
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• 2010

Purpose: Mitochondrial dysfunction can present with various symptoms depending on the organ it has affected. This research tried to analyze the ophthalmologic symptoms and ophthalmologic examination (OE) results in patients with mitochondrial disease (MD). Methods: Seventy-four patients diagnosed with mitochondrial respiratory chain complex defect with biochemical enzyme assay were included in the study. They were divided into 2 groups based on the OE results by funduscopy and were analyzed on the basis of their clinical features, biochemical test results, morphological analysis, and neuroimaging findings. Results: Thirty-seven (50%) of the 74 MD patients developed ophthalmologic symptoms. Abnormal findings were observed in 36 (48.6%) patients during an OE, and 16 (21.6%) of them had no ocular symptoms. Significantly higher rates of prematurity, clinical history of epilepsy or frequent apnea events, abnormal light microscopic findings in muscle pathology, diffuse cerebral atrophy in magnetic resonance imaging, and brainstem hyperintensity and lactate peaks in magnetic resonance spectroscopy were noted in the group with abnormal OE results. Conclusion: Although the ophthalmologic symptoms are not very remarkable in MD patients, an OE is required. When the risk factors mentioned above are observed, a more active approach should be taken in the OE because a higher frequency of ocular involvement can be expected.

• Journal of Microbiology
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• v.41 no.1
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• pp.41-45
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• 2003

N crassa mutant strain nap showed reduced growth rate, decreased electric membrane potential, and elevated intracellular ATP content in comparison to the wild type. Blue light induced a hyperpolarization of the membrane potential in both strains. The analysis of oxidative and phosphorylation activities of mitochondria isolated from the two strains has revealed that nap utilized more efficient oxidative pathways. The higher intracellular ATP content in the nap was presumably due to impaired transport systems of the plasma membrane, and to a lesser extent to the functioning of the fully competent respiratory chain. The excess ATP possibly accounts for carotenoid accumulation in the mutant.

• Journal of Photoscience
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• v.1 no.1
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• pp.9-14
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• 1994

Exposure of isolated intact mitochondria to near UV to visible light resulted in not only loss of respiration, the most well-documented phenomenon regarding phototoxic effects in the respiring organelles, but also lipid peroxidation of membranes and mitochondrial swelling; these turned out to be O$_2$-dependent and thus prevented by anaerobiosis, enhanced by a partial deuteration of the suspension medium, and suppressed by the presence of a singlet oxygen ($^1O_2$) scavenger. Measurements of the spectral dependence of such detrimental effects of light on mitochondrial structure and function revealed that all the resulting spectra bear a significant resemblance to the action spectrum for photogeneration of $^1O_2$ from mitochondrial membranes, which in turn carries the spectral characteristics of light absorption by mitochondrial Fe-S centers. Futhermore, destructing the Fe-S centers by a mercurial treatment of mitochondria brought about a striking reduction of the light-induced membrane peroxidation and swelling of mitochondria. These results are consistent with the suggestion that the impairment of functional, structural integrity of mitochondria caused by strong irradiation is directly related to the production of $^1O_2$ in mitochondria, photosensitized by the Fe-S centers. This paper also presents kinetic data which indicate that, among various membrane-bound protein systems associated with mitochondrial energy metabolism, the respiratory chain is the primary target for photodamage.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.2
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• pp.72-77
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• 2015

Purpose: Deficits of the respiratory chain are reported to be the major cause of Leigh syndrome is said to be the underlying causes. The need for biochemical diagnosis to draw more accurate diagnosis or prognosis to support treatments is rapidly increasing. This study tried to analyze the aspects of clinical characteristics and biochemical diagnosis of mitochondrial respiratory chain complex (MRC) defect in Leigh syndrome, using methods of biochemical enzyme assay. Methods: We included total number of 47 patients who satisfied the clinical criteria of Leigh syndrome and confirmed by biochemical diagnosis. All those patients went through muscle biopsy to perform biochemical enzyme assay to analyze MRC enzyme in order to find the underlying cause of Leigh syndrome. Results: MRC I defect was seen in 23 (48.9%) cases taking the first place and MRC IV defect in 15 (31.9%) following it. There were 9 (19.2%) cases of combined MRC defect. Combined cases of type I and IV were detected in 7 (14.9%) patients while type I and V in 2 (4.3%). The onset age of symptom was less than 1 year old in 28 (59.6%). The most common early symptom, observed in 23 (48.9%), was delayed development, but there were other various neurological symptoms observed as well. In regard with the disease progression, 35 (74.5%) patients showed slowly progressive course, the one that progressed continuously but slowly over 2 years of period. As for Maximum motor development, 22 (46.8%) were bed-ridden state, most of them suffering serious delayed development. Patients showed various symptoms with different organs involved, though neuromuscular involvement was most prominent. Delayed development was seen in all cases. Multifocal lesion in brain MRI study was seen in 36 (76.6 %) cases, taking a greater percentage than 11 (23.4%) cases with single lesion. In MR spectroscopy study, the characteristic lactate peak of mitochondrial disease was identified in 20 (42.6%) patients. Conclusions: Further analysis of clinical and biochemical diagnosis on more extended group of patients with Leigh syndrome will enable us to improve diagnostic precision and to understand the natural course of mitochondrial disease.

• BMB Reports
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• v.42 no.11
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• pp.719-724
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• 2009

Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.2
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• pp.191-194
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• 2014

Mitochondrial myopathy results from a primary dysfunction of the respiratory chain and is frequently accompanied with endocrine manifestations. Among the endocrine manifestations of mitochondrial disease, diabetes mellitus is relatively common. Diabetes mellitus in the mitochondrial myopathy is usually insulin dependent due to the defect in insulin secretion resulted from mitochondrial dysfunction. But it is seldom manifested as diabetes ketoacidosis and doesn't usually have an auto-antibody. We report a patient with mitochondrial myopathy who was diagnosed as having diabetes mellitus by presenting as diabetes ketoacidosis and had both of the auto-glutamic acid decarboxylase (GAD) antibody and anti-insulin auto-antibody.