• Molecules and Cells
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• v.41 no.1
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• pp.55-64
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• 2018

Autophagy is an intracellular degradation pathway for large protein aggregates and damaged organelles. Recent studies have indicated that autophagy targets cargoes through a selective degradation pathway called selective autophagy. Peroxisomes are dynamic organelles that are crucial for health and development. Pexophagy is selective autophagy that targets peroxisomes and is essential for the maintenance of homeostasis of peroxisomes, which is necessary in the prevention of various peroxisome-related disorders. However, the mechanisms by which pexophagy is regulated and the key players that induce and modulate pexophagy are largely unknown. In this review, we focus on our current understanding of how pexophagy is induced and regulated, and the selective adaptors involved in mediating pexophagy. Furthermore, we discuss current findings on the roles of pexophagy in physiological and pathological responses, which provide insight into the clinical relevance of pexophagy regulation. Understanding how pexophagy interacts with various biological functions will provide fundamental insights into the function of pexophagy and facilitate the development of novel therapeutics against peroxisomal dysfunction-related diseases.

• Journal of Plant Biology
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• v.27 no.4
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• pp.241-251
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• 1984

The present study investigated the effects of triacontanol (TRIA) on plant growth and peroxisomal enzyme activities in radish seedlings. The optimum concentration of TRIA with respect to radish seedling bioassay was decided to 1.0mg $1^{-1}$. In comparison to untreated controls (including Tween 20 treatment), 1.0mg $1^{-1}$ TRIA treatment caused an increase in seed germination rate and root growth, but no stimulation in hypocotyl growth. Chlorophyll accumulation in cotyledon during carly development stage increased rapidly, and degradation of chlorophyll in later stage due to the cotyledon senesence was noticeably retarded. Increase of soluble protein content in cotyledon at early period of development was observed. Isocitrate lyase and catalase activity was not significantly different in both the treated and the untreated plants. But, glycolate oxidase activity was inhibited by TRIA down to 20% against controls. Also, the increase of the activity of peroxidase, a leaf-senescence marker enzyme, was continuously retarded over control for 8 days of development. Based on above results, TRIA was found to be active in both the growth and the peroxisomal enzyme activities of radish seedlings.

• BMB Reports
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• v.42 no.5
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• pp.281-285
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• 2009

Peroxisomes play an important role in cellular defense systems and generate secondary messengers for cellular communication. Saccharomyces cerevisiae containing oleate-induced peroxisomes were subjected to buffer-soluble extraction and two chromatographic procedures, and a protein with antifungal activity was isolated. The results of MALDI-TOF analysis identified the isolated protein as peroxisomal 3-ketoacyl-CoA thiolase (ScFox3). Purified yeast ScFox3 exhibited thiolase activity that catalyzed the thiolytic cleavage of 3-ketoacyl-CoA to acetyl-CoA and acyl-CoA. ScFox3 protein inhibited various pathogenic fungal strains, with the exception of Aspergillus flavus. Using ScFox3-GFP and PTS2 signal-truncated ScFox3M-GFP, we showed that only ScFox3-GFP, with an intact PTS2 peroxisome signal sequence, was able to translocate into peroxisomes. Yeast ScFox3 is a natural antifungal agent found in peroxisomes.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.49-53
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• 2012

X-linked adrenoleukodystrophy (ALD) is a rare inherited metabolic disease which results in impaired peroxisomal ${\beta}$-oxidation and the accumulation of very long chain fatty acids (VLCFA) in the adrenal cortex, the myelin of the central nervous system, and the testes. X-linked ALD is caused by mutations in the ABCD1 gene encoding an ATP-binding cassette transporter superfamily located in the peroxisomal membrane. This disease is characterized by a variety of phenotypes. The classic childhood cerebral ALD is a rapidly progressive demyelinating condition affecting the cerebral white matter before the age of 10 years in boys. We report the case of a 8-year-old with childhood cerebral X-linked ALD who developed inattention, hyperactivity, motor incoordination and hemiparesis. We diagnosed ALD with elevated plasma very long chain fatty acid level and diffuse high signal intensity lesions in both parieto-occipital white matter and cerebellar white matter in brain MRI. We identified a novel c.983delT (p.Met329CysfsX7) mutation of the ABCD1 gene. There is no correlation between X-ALD phenotype and mutations in the ABCD1 gene. Further studies for searching additional non-genetic factor which determine the phenotypic variation will be needed.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.2
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• pp.349-359
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• 2020

Objective: Orchastric changes in the mammary glands are vital, especially during lactation. The secretary epithelial cells together with the supporting myoepithelial and stromal cells function cordially to secrete milk. Increase in the number of luminal epithelial cells and a decrease in adipocytes are visible during lactation, whereas the reverse happens in the involution. However, an early involution occurs if the epithelial cells transdifferentiate towards adipocytes during the lactation period. We aimed to inhibit the adipocyte transdifferentiation of luminal cells by restraining the peroxisomal proliferator-activated receptor γ (PPARγ) pathway. Methods: Linolenic acid (LA) and thiazolidinediones (TZDs) induced adipogenesis in mammary epithelial cells were conducted in monolayer, mixed culture as well as in transwell plate co-culture with mammary myoepithelial cells. Results: Co-culture with myoepithelial cells showed higher adipogenic gene expression in epithelial cells under LA+TZDs treatment. Increase in the expressions of PPARγ, CCAAT/enhancer-binding protein α and vimentin in both mRNA as well as protein levels were observed. Whereas, bisphenol A diglycidyl ether treatment blocked LA+TZDs induced adipogenesis, as it could not show a significant rise in adipose related markers. Although comparative results were found in both mixed culture and monolayer conditions, co-culture technic was found to work better than the others. Conclusion: Antagonizing PPARγ pathway in the presence of myoepithelial cells can significantly reduce the adipogenisis in epithelial cells, suggesting therapeutic inhibition of PPARγ can be considered to counter early involution or excessive adipogenesis in mammary epithelium in animals.

• BMB Reports
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• v.52 no.9
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• pp.566-571
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• 2019

Lymphoma is one of the most curable types of cancer. However, drug resistance is the main challenge faced in lymphoma treatment. Peroxisomal acyl-CoA oxidase 1 (ACOX1) is the rate-limiting enzyme in fatty acid ${\beta}$-oxidation. Deregulation of ACOX1 has been linked to peroxisomal disorders and carcinogenesis in the liver. Currently, there is no information about the function of ACOX1 in lymphoma. In this study, we found that upregulation of ACOX1 promoted proliferation in lymphoma cells, while downregulation of ACOX1 inhibited proliferation and induced apoptosis. Additionally, overexpression of ACOX1 increased resistance to doxorubicin, while suppression of ACOX1 expression markedly potentiated doxorubicin-induced apoptosis. Interestingly, downregulation of ACOX1 promoted mitochondrial location of Bad, reduced mitochondrial membrane potential and provoked apoptosis by activating caspase-9 and caspase-3 related apoptotic pathway. Overexpression of ACOX1 alleviated doxorubicin-induced activation of caspase-9 and caspase-3 and decrease of mitochondrial membrane potential. Importantly, downregulation of ACOX1 increased p73, but not p53, expression. p73 expression was critical for apoptosis induction induced by ACOX1 downregulation. Also, overexpression of ACOX1 significantly reduced stability of p73 protein thereby reducing p73 expression. Thus, our study indicated that suppression of ACOX1 could be a novel and effective approach for treatment of lymphoma.

• Journal of Microbiology and Biotechnology
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• v.24 no.2
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• pp.152-159
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• 2014

The regulation of protein tyrosine phosphorylation is mediated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) and is essential for cellular homeostasis. Co-expression of PTKs with PTPs in Pichia pastoris was used to facilitate the expression of active PTKs by neutralizing their apparent toxicity to cells. In this study, the gene encoding phosphatase PTP1B with or without a blue fluorescent protein or peroxisomal targeting signal 1 was cloned into the expression vector pAG32 to produce four vectors. These vectors were subsequently transformed into P. pastoris GS115. The tyrosine kinases EGFR-2 and $PDGFR{\beta}$ were expressed from vector pPIC3.5K and were fused with a His-tag and green fluorescent protein at the N-terminus. The two plasmids were transformed into P. pastoris with or without PTP1B, resulting in 10 strains. The EGFR-2 and $PDGFR{\beta}$ fusion proteins were purified by $Ni^{2+}$ affinity chromatography. In the recombinant P. pastoris, the PTKs co-expressed with PTP1B exhibited higher kinase catalytic activity than did those expressing the PTKs alone. The highest activities were achieved by targeting the PTKs and PTP1B into peroxisomes. Therefore, the EGFR-2 and $PDGFR{\beta}$ fusion proteins expressed in P. pastoris may be attractive drug screening targets for anticancer therapeutics.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.1
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• pp.7-12
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• 2010

The full-length cDNA of the porcine peroxisomal ${\Delta}^3$,${\Delta}^2$-enoyl-CoA isomerase (PECI) gene encodes a monofunctional peroxisomal ${\Delta}^3$,${\Delta}^2$-enoyl-CoA isomerase. Cloning and sequencing of the porcine PECI cDNA revealed the presence of an 1185-base pair open reading frame predicted to encode a 394-amino acid protein by the 5'rapid amplification of cDNA ends (5'RACE) and EST sequences. The porcine PECI gene was expressed in seven tissues (heart, liver, spleen, lung, kidney, skeletal muscle, fat) which was revealed by reverse transcriptase-polymerase chain reaction (RT-PCR). The porcine PECI was mapped to SSC71/2 p11-13 using the somatic cell hybrid panel (SCHP) and the radiation hybrid panel (RH) (LOD score 12.84). The data showed that PECI was closely linked to marker S0383. A C/T single nucleotide polymorphism in PECI exon 10 (3'UTR) was detected as a PvuII PCR-RFLP. Association analysis in our experimental pig population showed that different genotypes of PECI gene were significantly associated with the Average Backfat thickness (ABF) (p<0.05) and Buttock backfat thickness (p<0.01).

• Molecules and Cells
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• v.38 no.2
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• pp.187-194
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• 2015

Thioredoxin (TRX) is a disulfide reductase present ubiquitously in all taxa and plays an important role as a regulator of cellular redox state. Recently, a redox-independent, chaperone function has also been reported for some thioredoxins. We previously identified nodulin-35, the subunit of soybean uricase, as an interacting target of a cytosolic soybean thioredoxin, GmTRX. Here we report the further characterization of the interaction, which turns out to be independent of the disulfide reductase function and results in the co-localization of GmTRX and nodulin-35 in peroxisomes, suggesting a possible function of GmTRX in peroxisomes. In addition, the chaperone function of GmTRX was demonstrated in in vitro molecular chaperone activity assays including the thermal denaturation assay and malate dehydrogenase aggregation assay. Our results demonstrate that the target of GmTRX is not only confined to the nodulin-35, but many other peroxisomal proteins, including catalase (AtCAT), transthyretin-like protein 1 (AtTTL1), and acyl-coenzyme A oxidase 4 (AtACX4), also interact with the GmTRX. Together with an increased uricase activity of nodulin-35 and reduced ROS accumulation observed in the presence of GmTRX in our results, especially under heat shock and oxidative stress conditions, it appears that GmTRX represents a novel thioredoxin that is co-localized to the peroxisomes, possibly providing functional integrity to peroxisomal proteins.

• Molecules and Cells
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• v.37 no.1
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• pp.74-80
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• 2014

The peroxisome is an intracellular organelle that responds dynamically to environmental changes. Various model organisms have been used to study the roles of peroxisomal proteins in maintaining cellular homeostasis. By taking advantage of the zebrafish model whose early stage of embryogenesis is dependent on yolk components, we examined the developmental roles of the D-bifunctional protein (Dbp), an essential enzyme in the peroxisomal ${\beta}$-oxidation. The knockdown of dbp in zebrafish phenocopied clinical manifestations of its deficiency in human, including defective craniofacial morphogenesis, growth retardation, and abnormal neuronal development. Overexpression of murine Dbp rescued the morphological phenotypes induced by dbp knockdown, indicative of conserved roles of Dbp during zebrafish and mammalian development. Knockdown of dbp impaired normal development of blood, blood vessels, and most strikingly, endoderm-derived organs including the liver and pancreas - a phenotype not reported elsewhere in connection with peroxisome dysfunction. Taken together, our results demonstrate for the first time that zebrafish might be a useful model animal to study the role of peroxisomes during vertebrate development.