Glycogen storage disease phenotypes accompanying the perturbation of the methionine cycle in NDRG3-deficient mouse livers

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dc.contributor.authorHyun Ahm Sohn-
dc.contributor.authorDong Chul Lee-
dc.contributor.authorAnna Park-
dc.contributor.authorMinho Kang-
dc.contributor.authorByoung-Ha Yoon-
dc.contributor.authorChul-Ho Lee-
dc.contributor.authorYong-Hoon Kim-
dc.contributor.authorKyoung-Jin Oh-
dc.contributor.authorCha Yeon Kim-
dc.contributor.authorSeong-Hwan Park-
dc.contributor.authorHan Koo-
dc.contributor.authorHyoung-Chin Kim-
dc.contributor.authorWoon Kee Yoon-
dc.contributor.authorD S Lim-
dc.contributor.authorD Kim-
dc.contributor.authorKyung Chan Park-
dc.contributor.authorYoung Il Yeom-
dc.date.accessioned2022-05-16T15:31:30Z-
dc.date.available2022-05-16T15:31:30Z-
dc.date.issued2022-
dc.identifier.issn2073-4409-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/26001-
dc.description.abstractN-Myc downstream regulated gene 3 (NDRG3) is a unique pro-tumorigenic member among NDRG family genes, mediating growth signals. Here, we investigated the pathophysiological roles of NDRG3 in relation to cell metabolism by disrupting its functions in liver. Mice with liver-specific KO of NDRG3 (Ndrg3 LKO) exhibited glycogen storage disease (GSD) phenotypes including excessive hepatic glycogen accumulation, hypoglycemia, elevated liver triglyceride content, and several signs of liver injury. They suffered from impaired hepatic glucose homeostasis, due to the suppression of fasting-associated glycogenolysis and gluconeogenesis. Consistently, the expression of glycogen phosphorylase (PYGL) and glucose-6-phosphate transporter (G6PT) was significantly down-regulated in an Ndrg3 LKO-dependent manner. Transcriptomic and metabolomic analyses revealed that NDRG3 depletion significantly perturbed the methionine cycle, redirecting its flux towards branch pathways to upregulate several metabolites known to have hepatoprotective functions. Mechanistically, Ndrg3 LKO-dependent downregulation of glycine N-methyltransferase in the methionine cycle and the resultant elevation of the S-adenosylmethionine level appears to play a critical role in the restructuring of the methionine metabolism, eventually leading to the manifestation of GSD phenotypes in Ndrg3 LKO mice. Our results indicate that NDRG3 is required for the homeostasis of liver cell metabolism upstream of the glucose-glycogen flux and methionine cycle and suggest therapeutic values for regulating NDRG3 in disorders with malfunctions in these pathways.-
dc.publisherMDPI-
dc.titleGlycogen storage disease phenotypes accompanying the perturbation of the methionine cycle in NDRG3-deficient mouse livers-
dc.title.alternativeGlycogen storage disease phenotypes accompanying the perturbation of the methionine cycle in NDRG3-deficient mouse livers-
dc.typeArticle-
dc.citation.titleCells-
dc.citation.number9-
dc.citation.endPage1536-
dc.citation.startPage1536-
dc.citation.volume11-
dc.contributor.affiliatedAuthorHyun Ahm Sohn-
dc.contributor.affiliatedAuthorDong Chul Lee-
dc.contributor.affiliatedAuthorAnna Park-
dc.contributor.affiliatedAuthorMinho Kang-
dc.contributor.affiliatedAuthorByoung-Ha Yoon-
dc.contributor.affiliatedAuthorChul-Ho Lee-
dc.contributor.affiliatedAuthorYong-Hoon Kim-
dc.contributor.affiliatedAuthorKyoung-Jin Oh-
dc.contributor.affiliatedAuthorCha Yeon Kim-
dc.contributor.affiliatedAuthorSeong-Hwan Park-
dc.contributor.affiliatedAuthorHan Koo-
dc.contributor.affiliatedAuthorHyoung-Chin Kim-
dc.contributor.affiliatedAuthorWoon Kee Yoon-
dc.contributor.affiliatedAuthorKyung Chan Park-
dc.contributor.affiliatedAuthorYoung Il Yeom-
dc.contributor.alternativeName손현암-
dc.contributor.alternativeName이동철-
dc.contributor.alternativeName박안나-
dc.contributor.alternativeName강민호-
dc.contributor.alternativeName윤병하-
dc.contributor.alternativeName이철호-
dc.contributor.alternativeName김용훈-
dc.contributor.alternativeName오경진-
dc.contributor.alternativeName김차연-
dc.contributor.alternativeName박성환-
dc.contributor.alternativeName구한-
dc.contributor.alternativeName김형진-
dc.contributor.alternativeName윤원기-
dc.contributor.alternativeName임대식-
dc.contributor.alternativeName김대수-
dc.contributor.alternativeName박경찬-
dc.contributor.alternativeName염영일-
dc.identifier.bibliographicCitationCells, vol. 11, no. 9, pp. 1536-1536-
dc.identifier.doi10.3390/cells11091536-
dc.subject.keywordNDRG3-
dc.subject.keywordGlycogen storage disease-
dc.subject.keywordPYGL-
dc.subject.keywordMethionine cycle-
dc.subject.keywordReprogramming-
dc.subject.keywordGNMT-
dc.subject.localNDRG3-
dc.subject.localGlycogen storage disease-
dc.subject.localPYGL-
dc.subject.localMethionine cycle-
dc.subject.localreprogramming-
dc.subject.localReprogramming-
dc.subject.localGNMT-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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