• Title/Summary/Keyword: Mitochondrial RNA

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RUNX1 Upregulation Causes Mitochondrial Dysfunction via Regulating the PI3K-Akt Pathway in iPSC from Patients with Down Syndrome

  • Yanna Liu;Yuehua Zhang;Zhaorui Ren;Fanyi Zeng;Jingbin Yan
    • Molecules and Cells
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    • v.46 no.4
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    • pp.219-230
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    • 2023
  • Down syndrome (DS) is the most common autosomal aneuploidy caused by trisomy of chromosome 21. Previous studies demonstrated that DS affected mitochondrial functions, which may be associated with the abnormal development of the nervous system in patients with DS. Runt-related transcription factor 1 (RUNX1) is an encoding gene located on chromosome 21. It has been reported that RUNX1 may affect cell apoptosis via the mitochondrial pathway. The present study investigated whether RUNX1 plays a critical role in mitochondrial dysfunction in DS and explored the mechanism by which RUNX1 affects mitochondrial functions. Expression of RUNX1 was detected in induced pluripotent stem cells of patients with DS (DS-iPSCs) and normal iPSCs (N-iPSCs), and the mitochondrial functions were investigated in the current study. Subsequently, RUNX1 was overexpressed in N-iPSCs and inhibited in DS-iPSCs. The mitochondrial functions were investigated thoroughly, including reactive oxygen species levels, mitochondrial membrane potential, ATP content, and lysosomal activity. Finally, RNA-sequencing was used to explore the global expression pattern. It was observed that the expression levels of RUNX1 in DS-iPSCs were significantly higher than those in normal controls. Impaired mitochondrial functions were observed in DS-iPSCs. Of note, overexpression of RUNX1 in N-iPSCs resulted in mitochondrial dysfunction, while inhibition of RUNX1 expression could improve the mitochondrial function in DS-iPSCs. Global gene expression analysis indicated that overexpression of RUNX1 may promote the induction of apoptosis in DS-iPSCs by activating the PI3K/Akt signaling pathway. The present findings indicate that abnormal expression of RUNX1 may play a critical role in mitochondrial dysfunction in DS-iPSCs.

Integrative analysis of microRNA-mediated mitochondrial dysfunction in hippocampal neural progenitor cell death in relation with Alzheimer's disease

  • A Reum Han;Tae Kwon Moon;Im Kyeung Kang;Dae Bong Yu;Yechan Kim;Cheolhwan Byon;Sujeong Park;Hae Lin Kim;Kyoung Jin Lee;Heuiran Lee;Ha-Na Woo;Seong Who Kim
    • BMB Reports
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    • v.57 no.6
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    • pp.281-286
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    • 2024
  • Adult hippocampal neurogenesis plays a pivotal role in maintaining cognitive brain function. However, this process diminishes with age, particularly in patients with neurodegenerative disorders. While small, non-coding microRNAs (miRNAs) are crucial for hippocampal neural stem (HCN) cell maintenance, their involvement in neurodegenerative disorders remains unclear. This study aimed to elucidate the mechanisms through which miRNAs regulate HCN cell death and their potential involvement in neurodegenerative disorders. We performed a comprehensive microarray-based analysis to investigate changes in miRNA expression in insulin-deprived HCN cells as an in vitro model for cognitive impairment. miR-150-3p, miR-323-5p, and miR-370-3p, which increased significantly over time following insulin withdrawal, induced pronounced mitochondrial fission and dysfunction, ultimately leading to HCN cell death. These miRNAs collectively targeted the mitochondrial fusion protein OPA1, with miR-150-3p also targeting MFN2. Data-driven analyses of the hippocampi and brains of human subjects revealed significant reductions in OPA1 and MFN2 in patients with Alzheimer's disease (AD). Our results indicate that miR-150-3p, miR-323-5p, and miR-370-3p contribute to deficits in hippocampal neurogenesis by modulating mitochondrial dynamics. Our findings provide novel insight into the intricate connections between miRNA and mitochondrial dynamics, shedding light on their potential involvement in conditions characterized by deficits in hippocampal neurogenesis, such as AD.

Mitochondrial Dysfunction and Cancer (미토콘드리아 기능 이상과 암)

  • Han, Yu-Seon;Jegal, Myeong-Eun;Kim, Yung-Jin
    • 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.

Phylogenetic relationships among Acanthamoeba spp. based on PCR-RFLP analyses of mitochondrial small subunit rRNA gene

  • Yu, Hak-Sun;Hwang, Mee-Yul;Kim, Tae-Olk;Yun, Ho-Cheol;Kim, Tae-Ho;Kong, Hyun-Hee;Chung, Dong-Il
    • Parasites, Hosts and Diseases
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    • v.37 no.3
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    • pp.181-188
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    • 1999
  • We investigated the value of mitochondrial small subunit rRNA gene (mt SSU rDNA) PCR-RFLP as a taxonomic tool for Acanthamoeba isolates with close inter-relationships. Twenty-five isolates representing 20 species were included in the analysis. As in nuclear 18s rDNA analysis, two type strains (A. astronyxis and A. tubiashi) of morphological group 1 diverged earliest from the other strains, but the divergence between them was less than in 18s riboprinting. Acanthamoeba griffini of morhological group 2 branched between pathogenic (A. culbertsoni A-1 and A. healyi OC-3A) and nonpathogenic (A.palestinensis Reich, A. pustulosa GE-3a, A. royreba Oak Ridge, and A lenticulata PD2S) strains of morphological group 3. Among the remaining isolates of morphological group 2, the Chang strain had the identical mitochondrial riboprints as the type strain of A. hatchetti. AA2 and AA1, the type strains of A. divionensis and A. paradivionensis, respectively, had the identical riboprints as A. quina Vil3 and A. castellanii Ma. Although the branching orders of A. castellanii Neff, A. polyphaga P23, A. triangularis SH621, and A. lugdunensis L3a were different from those in 18S riboprinting analysis, the results obtained from this study generally coincided well with those from 18S riboprinting. Mitochondrial riboprinting may have an advantage over nuclear 18S rDNA riboprinting beacuse the mt SSU rDNAs do not seem to have introns that are found in the 18S genes of Acanthamoeba and that distort phylogenetic analyses.

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Anti-Inflammatory Effect of the Extracts from Leaves and Stems of Thymus quinquecistatus var. japonica (H.Hara) (섬백리향 잎과 줄기 추출물의 항염 활성에 관한 세포생물학적 연구)

  • Lee, Sun-Mi;Baek, Jeong-In
    • The Korea Journal of Herbology
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    • v.36 no.5
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    • pp.125-133
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    • 2021
  • Objectives : Thymus quinquecistatus var. japonica (H.Hara) is a member of the genus Thymus of perennial aromatic herb, and it's designated as a natural monument of South Korea. It has traditionally been known to have protective or therapeutic effects on various human disease including cerebrovascular and neurological disease. Recently it was suggested that essential oil extracted from thyme has anti-fungal and anti-bacterial effect. The aim of this study is to investigate anti-inflammatory effect of Thymus quinquecistatus var. japonica in Raw 264.7 macrophage cell line. Methods : The cytotoxic effects of water and 70% ethanol extracts from Thymus quinquecistatus var. japonica, was tested using MTT assay. Inhibitory effects of the extracts to nitric oxide production and mRNA expression of inflammatory cytokines were examined by RT-PCR. Also, MitoSOX-red assay and JC-1 assay were performed to determine if the extracts can inhibit mitochondrial ROS accumulation and maintain mitochondrial membrane potential. Results : In LPS-induced inflammatory response, the extracts efficiently reduced nitric oxide NO production through inhibiting mRNA expression of iNOS enzyme. In addition, expression of the proinflammatory cytokines, IL-1𝛽 and IL-6, was also down-regulated by the extract treatments. Excessive accumulation of mitochondrial ROS induced by LPS was inhibited in the extract treated cells, which finally protected mitochondrial membrane potential. Conclusions : These results showed that water and 70% ethanol extracts from Thymus quinquecistatus var. japonica have anti-inflammatory effect through down regulation of IL-1𝛽, IL-6, and iNOS, and also have antioxidative effect against mitochondrial ROS accumulation that promote inflammatory response.

Phylogenetic Relationship and DNA Polymorphism of Boleophthalmus pectinirostris and Scartelaos gigas (Teleostei: Gobiidae) of Korea (한국산 짱뚱어(Boleophthalmus pectinirostris)와 남방짱뚱어(Scartelaos gigas) (Gobiidae)의 분자유전학적 계통연관과 DNA 다형화)

  • Choi, Ki Ho;Chung, Ee Yung;Park, Gab Man
    • Korean Journal of Ichthyology
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    • v.25 no.3
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    • pp.149-156
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    • 2013
  • Phylogenetic relationships and DNA polymorphism among local populations of two Korean gobiidae species: Boleophthalmus pectinirostris and Scartelaos gigas were investigated based on 12S and 16S mitochondrial DNA and mitochondrial cytochrome b DNA sequences. DNA polymorphisms of B. pectinirostris between Suncheon and Gunsan populations were 100% identity from 434 bp segment of 12S rRNA gene and from 444 bp segment of mitochondrial cytochrome b genes, and 99.6% (2 bp different) identity from 484 bp segments of 16S rRNA genes. These results indicated the long period of geographic isolation between two populations of B. pectinirostris in Korea caused such high degrees of DNA polymorphisms. Based on the phylogenetic tree constructed from the two gobiid species in Korea, two genetically distinct groups of B. pectinirostris and S. gigas groups were recognized.

Mitochondrial Genome Sequence of Echinostoma revolutum from Red-Crowned Crane (Grus japonensis)

  • Ran, Rongkun;Zhao, Qi;Abuzeid, Asmaa M.I.;Huang, Yue;Liu, Yunqiu;Sun, Yongxiang;He, Long;Li, Xiu;Liu, Jumei;Li, Guoqing
    • Parasites, Hosts and Diseases
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    • v.58 no.1
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    • pp.73-79
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    • 2020
  • Echinostoma revolutum is a zoonotic food-borne intestinal trematode that can cause intestinal bleeding, enteritis, and diarrhea in human and birds. To identify a suspected E. revolutum trematode from a red-crowned crane (Grus japonensis) and to reveal the genetic characteristics of its mitochondrial (mt) genome, the internal transcribed spacer (ITS) and complete mt genome sequence of this trematode were amplified. The results identified the trematode as E. revolutum. Its entire mt genome sequence was 15,714 bp in length, including 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and one non-coding region (NCR), with 61.73% A+T base content and a significant AT preference. The length of the 22 tRNA genes ranged from 59 bp to 70 bp, and their secondary structure showed the typical cloverleaf and D-loop structure. The length of the large subunit of rRNA (rrnL) and the small subunit of rRNA (rrnS) gene was 1,011 bp and 742 bp, respectively. Phylogenetic trees showed that E. revolutum and E. miyagawai clustered together, belonging to Echinostomatidae with Hypoderaeum conoideum. This study may enrich the mitochondrial gene database of Echinostoma trematodes and provide valuable data for studying the molecular identification and phylogeny of some digenean trematodes.

The Effect of Aerobic Exercise Training Versus Resveratrol Supplementation on Mitochondrial Biogenesis in Skeletal Muscle of High-fat Diet-induced Obese Mice (고지방식이로 유도된 비만 쥐의 골격근에서 유산소 운동 훈련 또는 레스베라트롤 투여가 미토콘드리아 생합성에 미치는 영향)

  • Kim, Kyung-Il;An, Sang-Min;Park, Hee-Geun;Lee, Wang-Lok
    • Journal of Life Science
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    • v.29 no.8
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    • pp.837-845
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    • 2019
  • The purpose of this study was to analyze the effects of aerobic exercise and resveratrol supplementation on mitochondrial biogenesis in skeletal muscle of high-fat diet-induced obese mice. In this study, 4-wk-old C57BL/6 male mice were divided into four groups, with 10 animals in each group: a normal diet group (NC), high-fat diet group (HC), high-fat diet group with resveratrol supplementation (HRe), and high-fat diet GROUP with exercise (HE). Aerobic exercise was performed on a treadmill for 40~60 min/d at 10~14 m/min, 0% grade, 4 d/wk for 16 wk. Resveratrol (25 mg/kg bodyweight) was administrated once a day, 4 d/wk for 16 wk. There was a significance difference in COX-IV mRNA expression in the NC group versus that in the HC group (p<0.05). The expression of the SIRT-3, PGC-1a, and COX-IV mRNA genes in the HE group increased significantly as compared with the expression of these genes in the HC and HRe groups (p<0.05). These results indicated that high- fat diet-induced obesity did not affect mitochondria biogenesis gene expression in skeletal muscle. In contrast, aerobic exercise training increased the expression of mitochondria biogenesis gene expression in skeletal muscle in high-fat diet-induced obese mice. These findings suggested that aerobic exercise but not resveratrol supplementation had a positive effect on mitochondrial biogenesis in skeletal muscle in high-fat diet-induced obese mice.

Phylogenetic Analysis of Mitochondrial DNA Control Region in the Swimming Crab, Portunus trituberculatus

  • Cho, Eun-Min;Min, Gi-Sik;Kanwal, Sumaira;Hyun, Young-Se;Park, Sun-Wha;Chung, Ki-Wha
    • Animal cells and systems
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    • v.13 no.3
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    • pp.305-314
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    • 2009
  • The control region of mitochondrial DNA (13516-14619) is located between srRNA and $tRNA^{lle}$ gene in swimming crab, Portunus trituberculatus. The present study was investigated the genetic polymorph isms of the control region in samples of P. trituberculatus collected at coastal waters of the Yellow Sea in Korea. A total of 300 substitution and indel polymorphic sites were identified. In addition to SNPs and indel variation, a hypervariable microsatellite motif was also identified at position from 14358 to 14391, which exhibited 10 alleles including 53 different suballeles. When the hypervariable microsatellite motif was removed from the alignment, 95 haplotypes were identified (93 unique haplotypes). The nucleotide and haplotype diversities were ranged from 0.024 to 0.028 and from 0.952 to 1.000, respectively. The statistically significant evidence for geographical structure was not detected from the analyses of neighbor-joining tree and minimum-spanning network, neither. This result suggest that population of P. trituberculatus are capable of extensive gene flow among populations. We believed that the polymorph isms of the control region will be used for informative markers to study phylogenetic relationships of P. trituberculatus.

Intraspecific variation of gene structure in the mitochondrial large subunit ribosomal RNA and cytochrome c oxidase subunit 1 of Pyropia yezoensis (Bangiales, Rhodophyta)

  • Hwang, Il Ki;Kim, Seung-Oh;Hwang, Mi Sook;Park, Eun-Jeong;Ha, Dong-Soo;Lee, Sang-Rae
    • ALGAE
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    • v.33 no.1
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    • pp.49-54
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    • 2018
  • Red algal mitochondrial genomes (mtDNAs) can provide useful information on species identification. mtDNAs of Pyropia / Porphyra (Bangiales, Rhodophyta) have shown diverse variation in their size and gene structure. In particular, the introns and intronic open reading frames found in the ribosomal RNA large subunit gene (rnl) and cytochrome c oxidase subunit 1 gene (cox1) significantly vary the mitochondrial genome size in Pyropia / Porphyra species. In this study, we examined the exon / intron structure of rnl and cox1 genes of Pyropia yezoensis at the intraspecific level. The combined data of rnl and cox1 genes exhibited 12 genotypes for 40 P. yezoensis strains, based on the existence of introns. These genotypes were more effective to identify P. yezoensis strains in comparison to the traditional DNA barcode cox1 marker (5 haplotypes). Therefore, the variation in gene structure of rnl and cox1 can be a novel molecular marker to discriminate the strains of Pyropia species.