• BMB Reports
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• 제47권5호
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• pp.280-285
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• 2014

Cancer cells undergo uncontrolled proliferation, and aberrant mitochondrial alterations. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein. TRAP1 mRNA is highly expressed in some cancer cell lines and tumor tissues. However, the effects of its overexpression on mitochondria are unclear. In this study, we assessed mitochondrial changes accompanying TRAP1 overexpression, in a mouse cell line, NIH/3T3. We found that overexpression of TRAP1 leads to a series of mitochondrial aberrations, including increase in basal ROS levels, and decrease in mitochondrial biogenesis, together with a decrease in peroxisome proliferator-activated receptor gamma coactivator-$1{\alpha}$ (PGC-$1{\alpha}$) mRNA levels. We also observed increased extracellular signal-regulated kinase (ERK) phosphorylation, and enhanced proliferation of TRAP1 overexpressing cells. This study suggests that overexpression of TRAP1 might be a critical link between mitochondrial disturbances and carcinogenesis.

• Journal of Microbiology
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• 제37권4호
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• pp.229-233
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• 1999

The mitochondrial plasmid pMLP1 from a white-rot fungus, Pleurotus ostreatus, is a double-stranded DNA containing 381 bp terminal inverted repeat (TIR) whose 5'-ends are covalently bound by terminal proteins. The plasmid contains two major open reading frames (ORFs), encoding putative DNA and RNA polymerases, and a minor ORF encoding a small, highly basic protein. To identify the DNA binding activity that recognizes the TIR region of pMLP1, gel retardation assays were performed with mitochondrial extracts. A specific protein binding to a region between 123 and 248 nt within TIR was observed. We examined whether the gene product of mORF1 bindes to this region specifically. E. coli cell extract which contains an overproduced mORF1 protein formed a complex specific to the region between 123 and 248 nt. Inclusion of mORF1 protein in the specific complex formed between P. ostreatus mitochondrial extract and TIR was confirmed by a supershift assay using polyclonal antibodies against the mORF1 protein. Our result suggest that the product of mORF1 may function as a terminal region recognition factor (TRF), recognizing an internal region in TIR.

• 생명과학회지
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• 제31권12호
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• pp.1057-1065
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• 2021

위암 환자에서 미토콘드리아 DNA (mtDNA)의 양적 변화가 보고 되고 있으며 이러한 변화가 위암의 발암이나 진행에 관여되는 것으로 추정되고 있다. 그리나 위암에서 미토콘드리아 단백질이나 mtDNA에 의해 암호화된 산화적 인산화(OXPHOS) 단백질의 양적 변화에 관한 연구는 아직까지 미비한 실정이다. 본 연구에서는 위암환자 조직 및 세포주를 이용하여 mtDNA 양 그리고 미토콘드리아 단백질 및 OXPHOS 단백질의 양을 분석하였다. 또한, mtDNA 양적 변화와 위암 환자의 임상병리학적 특징을 연관 분석하였다. MtDNA 양을 분석하기 위하여 qPCR 기법을 그리고 단백질 분석에는 Western blot 기법을 각각 활용하였다. 총 27개의 위암 환자 샘플에서 약 80%에 해당하는 22개의 환자 위암조직에서 정상조직에 비해 mtDNA 양이 감소하였으며, 나머지 환자에서는 mtDNA 양이 증가하였다. 이러한 mtDNA 양이 감소한 위암 조직 샘플에서는 미토콘드리아 단백질 및 OXPHOS 단백질의 양도 같이 감소하였다. 한편, 본 연구에 사용된 총 5개의 위암 세포주 모두에서 mtDNA 양이 감소하였다 그러나 위암 세포주에서는 mtDNA 양적 감소와 미토콘드리아 단백질 및 OXPHOS 단백질의 양적 감소가 항상 일치하지는 않았다. 이러한 연구결과는 위암 조직 및 세포주에서 mtDNA 양의 감소가 흔하며 이는 mtDNA 양적 변화가 위암의 생성에 관여함을 제시한다.

• Biomolecules & Therapeutics
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• 제30권5호
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• pp.409-417
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• 2022

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, and accumulating evidence indicates that mitochondrial dysfunction is associated with progressive deterioration in PD patients. Previous studies have shown that sinapic acid has a neuroprotective effect, but its mechanisms of action remain unclear. The neuroprotective effect of sinapic acid was assayed in a PD mouse model generated by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as well as in SH-SY5Y cells. Target protein expression was detected by western blotting. Sinapic acid treatment attenuated the behavioral defects and loss of dopaminergic neurons in the PD models. Sinapic acid also improved mitochondrial function in the PD models. MPTP treatment increased the abundance of mitochondrial fission proteins such as dynamin-related protein 1 (Drp1) and phospho-Drp1 Ser616. In addition, MPTP decreased the expression of the REV-ERB α protein. These changes were attenuated by sinapic acid treatment. We used the pharmacological REV-ERB α inhibitor SR8278 to confirmation of protective effect of sinapic acid. Treatment of SR8278 with sinapic acid reversed the protein expression of phospho-Drp1 Ser616 and REV-ERB α on MPTP-treated mice. Our findings demonstrated that sinapic acid protects against MPTP-induced PD and these effects might be related to the inhibiting abnormal mitochondrial fission through REV-ERB α.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.879-879
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• 2005

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.867-867
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• 2005

• BMB Reports
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• 제56권12호
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• pp.663-668
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• 2023

C-reactive protein (CRP) is an inflammatory marker and risk factor for atherosclerosis and cardiovascular diseases. However, the mechanism through which CRP induces myocardial damage remains unclear. This study aimed to determine how CRP damages cardiomyocytes via the change of mitochondrial dynamics and whether survivin, an anti-apoptotic protein, exerts a cardioprotective effect in this process. We treated H9c2 cardiomyocytes with CRP and found increased intracellular ROS production and shortened mitochondrial length. CRP treatment phosphorylated ERK1/2 and promoted increased expression, phosphorylation, and translocation of DRP1, a mitochondrial fission-related protein, from the cytoplasm to the mitochondria. The expression of mitophagy proteins PINK1 and PARK2 was also increased by CRP. YAP, a transcriptional regulator of PINK1 and PARK2, was also increased by CRP. Knockdown of YAP prevented CRP-induced increases in DRP1, PINK1, and PARK2. Furthermore, CRP-induced changes in the expression of DRP1 and increases in YAP, PINK1, and PARK2 were inhibited by ERK1/2 inhibition, suggesting that ERK1/2 signaling is involved in CRP-induced mitochondrial fission. We treated H9c2 cardiomyocytes with a recombinant TAT-survivin protein before CRP treatment, which reduced CRP-induced ROS accumulation and reduced mitochondrial fission. CRP-induced activation of ERK1/2 and increases in the expression and activity of YAP and its downstream mitochondrial proteins were inhibited by TAT-survivin. This study shows that mitochondrial fission occurs during CRP-induced cardiomyocyte damage and that the ERK1/2-YAP axis is involved in this process, and identifies that survivin alters these mechanisms to prevent CRP-induced mitochondrial damage.

• BMB Reports
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• 제55권7호
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• pp.354-359
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• 2022

MitoNEET, a mitochondrial outer membrane protein containing the Asn-Glu-Glu-Thr (NEET) sequence, controls the formation of intermitochondrial junctions and confers autophagy resistance. Moreover, mitoNEET as a mitochondrial substrate undergoes ubiquitination by activated Parkin during the initiation of mitophagy. Therefore, mitoNEET is linked to the regulation of autophagy and mitophagy. Mitophagy is the selective removal of the damaged or unnecessary mitochondria, which is crucial to sustaining mitochondrial quality control. In numerous human diseases, the accumulation of damaged mitochondria by impaired mitophagy has been observed. However, the therapeutic strategy targeting of mitoNEET as a mitophagy-enhancing mediator requires further research. Herein, we confirmed that mitophagy is indeed activated by mitoNEET inhibition. CCCP (carbonyl cyanide m-chlorophenyl hydrazone), which leads to mitochondrial depolarization, induces mitochondrial dysfunction and superoxide production. This, in turn, contributes to the induction of mitophagy; mitoNEET protein levels were initially increased before an increase in LC3-II protein following CCCP treatment. Pharmacological inhibition of mitoNEET using mitoNEET Ligand-1 (NL-1) promoted accumulation of Pink1 and Parkin, which are mitophagy-associated proteins, and activation of mitochondria-lysosome crosstalk, in comparison to CCCP alone. Inhibition of mitoNEET using NL-1, or mitoNEET shRNA transfected into RAW264.7 cells, abrogated CCCP-induced ROS and mitochondrial cell death; additionally, it activated the expression of PGC-1α and SOD2, regulators of oxidative metabolism. In particular, the increase in PGC-1α, which is a major regulator of mitochondrial biogenesis, promotes mitochondrial quality control. These results indicated that mitoNEET is a potential therapeutic target in numerous human diseases to enhance mitophagy and protect cells by maintaining a network of healthy mitochondria.

• Journal of Nutrition and Health
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• 제37권9호
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• pp.786-793
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• 2004

Women with menopause or rats with ovariectomy is associated with increased body weight, body fat and insulin resistance, which are components of metabolic syndrome. Increased prevalence of metabolic syndrome after menopause might be associated with mitochondrial dysfunction, since mitochondrial oxidative and phosphorylation activity is strongly correlated with insulin sensitivity. Although estradiol replacement prevents the metabolic syndrome, harmful effect of estradiol hampers the casual usage to prevent the metabolic syndrome. It has been reported that genistein has a mild estrogenic activity, decreases fat mass in mice and has an antidiabetic role in diabetic rats. Although insulin resistance is closely related to mitochondrial functions, there has not been yet any study in regard to the effect of dietary genistein on mitochondrial function in the insulin resistant female subjects induced by ovariectomy or similar situation. The present study investigated whether the supplementation of genistein in the high fat diet affected the mitochondrial function of high fat fed ovariectomized rats. Female Sprague Dawley rats (8 weeks old) were assigned to the following groups: sham-operated+ high fat diet (S, n=6); sham-operated + high fat diet with 0.1% genistein (S + G, n=7); ovariectomized + high fat diet (OVX, n=8); ovariectomized + high fat diet with 0.1% genistein (OVX+ G, n=8). Ovariectomy significantly increased body weight compared with S group. Genistein consumption in ovariectomized (OVX + G) rats decreased body weight gain compared with OVX rats. Liver weights were increased by ovariectomy. The hepatic mitochondrial protein density expressed as mg per g liver was lower in the OVX group than in the S group. However, OVX + G group showed the increased mitochondrial protein density similar to the level of S group. When mRNA levels of genes related to mitochondria such as peroxisome proliferator-activated receptor ${\gamma}$ coactivator 1 (PGC-1) and cytochrome c oxidase subunit III (COX III) were measured, there were decreases in the mRNA levels of PGC-1 and COX III in S + G, OVX and OVX + G group. The activity of cytochrome c oxidase was not different between groups. We could observe the decrease in succinate dehydrogenase (SDH) activity per g liver in OVX rats. Genistein supplement increased SDH activity. In conclusion, genistein supplementation to the OVX rats enhanced mitochondrial function by increasing mitochondrial protein density and SDH activity. The improvement in mitochondrial function by genistein can contribute to the improvement in metabolic syndrome.

• Animal Systematics, Evolution and Diversity
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• 제26권3호
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• pp.197-201
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• 2010

We sequenced the whole mitochondrial genome of Dendronephthya gigantea (Anthozoa: Octocorallia: Nephteidae), the first mitochondrial genome sequence report in the Family Nephtheidae. The mitochondrial genome of D. gigantea was 18,842 bp in length, and contained 14 protein coding genes (atp6 and 8, cox1-3, cytb, nd1-6 and 4L, and msh1), two ribosomal RNAs, and only one transfer RNA. The gene content and gene order is identical to other octocorals sequenced to date. The portion of the noncoding regions is slightly larger than the other octocorals (5.08% compared to average 3.98%). We expect that the information of gene content, gene order, codon usage, noncoding region and protein coding gene sequence could be used in the further analysis of anthozoan phylogeny.