• Journal of Life Science
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• v.27 no.3
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• pp.361-369
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• 2017

Mitochondrial homeostasis is tightly regulated by two major processes: mitochondrial biogenesis and mitochondrial degradation by autophagy (mitophagy). Research in mitochondrial biogenesis in skeletal muscle in response to endurance exercise training has been well established, while the mechanisms regulating mitophagy and the relationship between mitochondrial biogenesis and degradation following endurance exercise training are not yet well defined. Studies have demonstrated that endurance exercise training increases the expression levels of mitochondrial biogenesis-, dynamics-, mitophagy-related genes in skeletal muscle. However, the increased levels of mitochondrial biogenesis marker proteins such as Cox IV and citrate synthase, by endurance exercise training were abolished when autophagy/mitophagy was inhibited in skeletal muscle. This suggests that both autophagy/mitophagy plays an important role in mitochondrial biogenesis/homeostasis and the coordination between the opposing processes may be important for skeletal muscle adaptation to endurance exercise training to improve metabolic function and endurance exercise performance. It is considered that endurance exercise training regulates each of these processes, mitochondrial biogenesis, fusion and fission events and autophagy/mitophagy, ensuring a relatively constant mitochondrial population. Exercise training may also have contributed to mitochondrial quality control which replaces old and/or unhealthy mitochondria with new and/or healthy ones in skeletal muscle. In this review paper, the molecular mechanisms regulating mitochondrial biogenesis and mitophagy and the coordination between the opposing processes is involved in the cellular adaptation to endurance exercise training in skeletal muscle will be discussed.

• Journal of Life Science
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• v.29 no.9
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• pp.1034-1046
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• 2019

The mitochondria is the major cellular organelle of energy metabolism for the supply of cellular energy; it also plays an important role in controlling calcium regulation, reactive oxygen species (ROS) production, and apoptosis. Mitochondrial dysfunction causes various diseases, such as neurodegenerative diseases, Lou Gehrig's disease, cardiovascular disease, mental disorders, diabetes, and cancer. Most of the diseases are age-related diseases. In this review, we focus on the roles of mitochondrial dysfunction in cancer. Mitochondrial dysfunction induces carcinogenesis and is found in many cancers. The factors that cause mitochondrial dysfunction differ depending on the types of carcinoma, and those factors could cause cancer malignancy, such as resistance to therapy and metastasis. Mitochondrial dysfunction is caused by a lack of mitochondria, an inability to provide key substances, or a dysfunction in the ATP synthesis machinery. The main factor associated with cancer malignancy is mtDNA depletion. Mitochondrial dysfunction would leads to malignancy through changes in molecular activity or expression, but it is not known in detail which changes lead to cancer malignancy. In order to explore the relationship between mitochondrial dysfunction and cancer malignancy in detail, mitochondria dysfunctional cell lines are constructed using chemical methods such as EtBr treatment or gene editing methods, including shRNA and CRISPR/Cas9. Those mitochondria dysfunctional cell lines are used in the study of various diseases caused by mitochondrial dysfunction, including cancer.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.1
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• pp.1-10
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• 2017

Purpose: This study aimed to investigate the perception and emotional experiences in rare and intractable diseases for caregivers of pediatric patients with mitochondrial diseases in order to provide therapeutic interventions for patients, caregivers, and families. Methods: A total of 83 caregivers of pediatric patients with mitochondrial diseases were recruited from the pediatric mitochondrial disease clinics of the Gangnam Severance Hospital in South Korea. Participants completed the survey about their perception of mitochondrial disease and emotional experiences after the diagnosis, and these clinical data were analyzed accordingly. Results: Surveys from a total of 83 caregivers of patients were analyzed, and the patients' age ranged from 6 to 12 years (33%), followed by ages 1 to 6 years (30%). Children with mitochondrial diseases were between 0 and 0.5 years of age at the time of first symptom onset (43%), and the duration of illness lasted more than 10 years in most cases (42%). Prior to diagnosis of mitochondrial diseases, the amount of awareness the caregivers had was 'Not at all' for both rare and intractable diseases and mitochondrial diseases in 44 cases and 68 cases, respectively. For the caregivers' emotional experiences, the most common initial responses were 'Discouraged/despair', 'Helpless/lethargic', and 'Disconcerted'. 'Anxious', 'Committed to treatment', and 'Responsibility as family members' were the most common emotional responses from the caregivers, followed by 'Disconcerted' and 'Helpless/lethargic'. Conclusion: It is important to consider the level of perception and emotional experiences of caregivers and patients with rare and intractable mitochondrial diseases for planning treatment programs.

• Journal of Life Science
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• v.27 no.5
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• pp.530-535
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• 2017

Mitochondria were isolated from bird and mammals. The activity of monoamine oxidase (EC 1.4.3.4) was then measured to identify mitochondrial isolation. Lactate dehydrogenase (EC 1.1.1.27, lactate dehydrogenase, LDH) isozymes in mitochondrial fractions were analyzed by biochemical and immunochemical methods. The activity of mitochondrial LDH was lower in mammals than in bird. Therefore, the role of mitochondrial LDH seems to be more important in bird than in mammals. The concentration of protein in all tissues of bird and mammals was less in the mitochondria than in the cytosol. In the cytosol of mice and golden hamsters, testis-specific LDH $C_4$ isozyme was expressed in testis in addition to the LDH $A_4$, $A_3B$, $A_2B_2$, $AB_3$, and $B_4$ isozymes. A single LDH AB hybrid isozyme was expressed in the chicken mitochondria. In mammals, mitochondrial LDH isozymes were differed according to tissues. LDH $A_4$ and testis-specific LDH $C_4$ isozymes were expressed in the mitochondria of mice. The mitochondrial testis-specific LDH $C_4$ isozyme was expressed only in the mice. In the golden hamster mitochondria, the LDH $B_4$ isozyme functioned as a lactate oxidase. As our results show, the mitochondrial LDH seemed to be playing the different role in the bird and mammals in relation with their metabolic conditions and habitats.

• Journal of Life Science
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• v.24 no.7
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• pp.791-797
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• 2014

Sixty-two conserved orthologous groups (OGs) of proteins, in 63 prokaryotes and seven eukaryotes were analyzed to identify essential proteins in the mitochondria of eukaryotes, and their counterparts in prokaryotes. Twenty OGs were common in eukaryotic mitochondria, and all were translation related. Encephalitozoon cuniculi, an obligate parasitic eukaryote, shares no common mitochondrial OGs with the other 69 organisms. Seventeen conserved OGs were mitochondria related in the 69 organisms. Mitochondria related- and nonrelated-OGs were divided into prokaryotic genomes (p<0.001, paired t-test) unlike eukaryotic genomes in the distance value analysis. The most commonly conserved mitochondria-related OG was COG0048-KOG1750 (ribosomal small subunit S12), whereas it was COG0100-KOG0407 (ribosomal small subunit S11) in nonrelated OGs. These results could be applied in scientific research to determine phylogenetic relationships and in areas such as drug development.

• The Korean Journal of Zoology
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• v.35 no.1
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• pp.70-79
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• 1992

미국흰불나방(Hyphontria cunea Drury) 종령유충과 나, 그리고 성충을 재료로하여 정세포가 정자로 변형되는 과정에서 나타나는 미토콘드리아의 분화과정을 전자현미경으로 관찰하였다. 다핵체를 이루고 있는 초기 정세포의 미토콘드리아는 축사가 형성되는 부위를 중심으로 집적된 후, 서로 유합되어 대형의 미토콘드리아 복합체인 부핵(Nebenkern)을 형성하였다. 부핵은 첨체형성 시기를 전후하여 세포의 장축을 따라서 길게 신장되며, 편모가 형성됨에 따라 축사를 중심으로 두께와 전자밀도가 서로 다른 두개의 미토콘드리아로 분리되었다. 분화가 계속됨에 따라서 서로 동일한 모양으로 변형된 미토콘드리아의 주변에서는 장축방향을 따라 다수의 미세소관이 분포하였고, 기질에서는 intramitochondrial crystalloid의 축적이 관찰되었다. 정자변형이 끝난 성숙정자의 미토콘드리아는 기질내부에 전자밀도가 높은 준결정물질이 함유된 미토콘드리아 유도체로 변형되었는데, 정자의 중편에서는 하나로 융합되어 있는 반면, 미부에서는 크기가 같은 두개의 유도체로 분리된 매우 독특한 형태로 관찰되었다.

• The Journal of the Korea Contents Association
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• v.9 no.4
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• pp.355-363
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• 2009

Increased oxidative stress by abnormal mitochondrial function can damage cell signal transduction and gene expression, and induce insulin resistance or diabetes. Autophagy, however, improve insulin resistance by clearance of malfunctioning mitochondria. Exercise also recovers the muscle dysfunction and degeneration by activating mitochondrial biogenesis. As it seems that exercise and autophagy might act as an orchestrated network to induce mitochondrial biogenesis, we investigated whether autophagy is involved in AMPK signal pathway stimulated by exercise or AICAR to increase mitochondrial biogenesis. And it showed that PGC-1 and mtTFA, but not autophagy marker LC3 mRNA expression were significantly increased by 6 hr of acute exercise. On the other hand, PGC-1 and mtTFA mRNA expression were upregulated by AICAR treatment to C2C12 myotube. However these genes were not inhibited by LC3 siRNA transfection. These results provide the evidence that autopahgy affects on mitochondrial biogenesis through different signal pathway from AMPK signal transduction.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.106-106
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• 2002

미토콘드리아는 세포내의 에너지대사에서 중요한 역할을 수행하는 세포내 소기관이며, 자체의 유전물질이 모계를 통해 유전되는 특징을 가지고 있다. 포유류 초기 배아의 발생과정에서 미토콘드리아의 역할과 기능에 대한 연구는 미진한 상태이다. 본 연구에서는 생쥐 초기 배아의 발생과정에서 관찰할 수 있는 미토콘드리아 미세구조의 변화 양상을 살펴보고, 이와 초기 배아의 발생 능력과의 관련성을 밝혀보고자 하였다. 과배란 유도된 ICR 생쥐로부터 배란된 난자와 2-세포기 배아를 수획하여 76 배양액으로 포배기까지 체외배양하면서, 각각의 발생단계에 따라 시료를 수획하였다. 미토콘드리아 미세구조의 변화는 일반적인 투과전자현미경방법(TEM)을 이용하여 관찰하였다. 미토콘드리아의 미세구조는 배란 난자에서 4-세포기 배아까지는 구형이고 크리스타가 발달하지 않은 원시형태였지만, 포배기로 발달함에 따라 크리스타가 발달된 막대형의 전형적인 미토콘드리아로 분화됨이 관찰되었다. 체외배양 중에 발생이 지연되거나 정지된 배아에서 관찰한 미토콘드리아의 미세구조는 공포화 (vacuolization), 크리스타 발달 지연, 손상된 미토콘드리아의 세포막 등과 같은 비정상적인 변형을 관찰할 수 있었다. 또한, 극체에 존재하는 미토콘드리아의 미세구조는 정상적인 핵내의 유전자와의 상호작용이 없어 미분화 상태로 포배기까지 유지되는 것을 관찰하였다. 이상의 결과를 통해 미토콘드리아의 정상적인 분화 과정이 초기 배아의 발생능력과 관련되어 있음을 알 수 있었으며, 포유류 초기 배아의 체외배양시스템을 개선하는데 미토콘드리아 미세구조의 관찰과 변화에 대한 고려가 있어야 될 것으로 생각된다. buffer A 용액으로 세척하여 유리 petri dish의 바닥에 부착된 macrophage만을 cell scraper로 분리하였다. 분리한 macrophage는 0.5-1 $\times$ $10^{6}$ cells/$m\ell$가 되게 조정하여, IL-I 을 0.001, 0.01, 0.1 또한 1 ng/$m\ell$를 첨가하여 농도에 따른 효과를 조사하였고, 각각 24, 48, 72, 96 또한 120시간을 배양하여 시간에 의한 효과도 실시하였다. 각 배치구에서 얻어진 배양액은 TGF-$\beta$를 조사하기 전까지 -2$0^{\circ}C$에 동결 보존하였다. TGF-$\beta$의 측정은 TGF-$\beta$ kit(promega, USA)를 이용하여 실시하였으며, 통계학적 분석은 Anova test를 Statview program을 이용하여 분석하였다. 시험의 결과 대조구에 비해 IL-I 첨가구는 2-3배의 TGF-$\beta$생산을 보였으며, 배양시간에 따른 생산은 시간이 지남에 따라 약간 상승하는 경향을 보였으나, 유의적인 차이를 보이지는 않았다. 또한 IL-I의 농도에 따른 생산의 변화는 IL-I의 농도에 따라 약간의 차이를 보였고 유의적인 차이는 인정되지 않았다. 임신 및 비임신의 경우 임신우의 비장 macrophage가 비임신보다는 약간 상승하는 거스로 나타났다. 이상의 결과로 볼 때 IL-I $\alpha$ 는$\bet

• Applied Microscopy
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• v.41 no.4
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• pp.249-255
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• 2011

Neurons utilize a large quantity of energy for their survival and function, and thereby require active mitochondrial function. Mitochondrial morphology shows dynamic changes, depending on the cellular condition, and mitochondrial dynamics are required for neuronal development and function. In this study, we found that the length of mitochondria in the distal axon is significantly shorter than that of mitochondria in dendrites or proximal axons of cerebral cortical neurons, and the reason for this difference is the local fission within the axon. We also found that suppression of Drp1, a key regulator of mitochondrial fission, resulted in significant elongation of mitochondria in axons. Collectively, these results suggest that local mitochondrial fission within the axon contributes to region-dependent mitochondrial length differences in the axons of cortical neurons.

• Proceedings of the Korean Society of Broadcast Engineers Conference
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• 2011.07a
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• pp.454-455
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• 2011

미토콘드리아의 수송은 치매, 다형성 경화증, 알츠하이머병 등의 신경성 질환과 관련하여 활발하게 연구되고 있다. 하지만 미토콘드리아 영상의 경우 일반 영상에 비해 노이즈(noise)가 많고 초당 프레임 수(frame-persecond)가 낮기 때문에 분석이 쉽지 않다. 이에 따라 미토콘드리아의 수송 통로인 축색돌기(axon)를 사전에 검출하고자 하는 연구들이 진행되고 있다. 본 논문에서는 이러한 배경을 바탕으로 미토콘드리아 영상에서 축색돌기를 자동으로 분리, 검출해내는 알고리즘을 제안한다. 배경이 비해 밝게 착색되어 있다는 미토콘드리아의 특성을 이용하여 축색돌기를 구분하는 데에 최대 화소값 기법(maximum intensity)과 혈관 증폭 필터(vessel enhancement filter)를 이용한다. 두 기법을 통해 얻은 축색돌기의 파편들은 로젠펠드 세선화(rosenfeld thinning)와 선형 보간법(linear interpolation)을 이용하여 연결되고 최종적인 검출 결과를 얻어낸다. 제시된 실험결과는 영상에서 전체적인 축색돌기가 성공적으로 검출되고 있음을 보여준다.