{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T02:23:03Z","timestamp":1762050183917,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation (NRF) of Korea","award":["NRF-2016M3A9E4947789","NRF-2017M3A9F9030565","NRF-2019R1A2C2008974","NRF-2022R1A2C3009475","KGM5192221"],"award-info":[{"award-number":["NRF-2016M3A9E4947789","NRF-2017M3A9F9030565","NRF-2019R1A2C2008974","NRF-2022R1A2C3009475","KGM5192221"]}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Science and ICT","doi-asserted-by":"publisher","award":["NRF-2016M3A9E4947789","NRF-2017M3A9F9030565","NRF-2019R1A2C2008974","NRF-2022R1A2C3009475","KGM5192221"],"award-info":[{"award-number":["NRF-2016M3A9E4947789","NRF-2017M3A9F9030565","NRF-2019R1A2C2008974","NRF-2022R1A2C3009475","KGM5192221"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003715","name":"KRIBB Research Initiative Program","doi-asserted-by":"publisher","award":["NRF-2016M3A9E4947789","NRF-2017M3A9F9030565","NRF-2019R1A2C2008974","NRF-2022R1A2C3009475","KGM5192221"],"award-info":[{"award-number":["NRF-2016M3A9E4947789","NRF-2017M3A9F9030565","NRF-2019R1A2C2008974","NRF-2022R1A2C3009475","KGM5192221"]}],"id":[{"id":"10.13039\/501100003715","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>N-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\u2013glycogen flux and methionine cycle and suggest therapeutic values for regulating NDRG3 in disorders with malfunctions in these pathways.<\/jats:p>","DOI":"10.3390\/cells11091536","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T08:21:25Z","timestamp":1651652485000},"page":"1536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Glycogen Storage Disease Phenotypes Accompanying the Perturbation of the Methionine Cycle in NDRG3-Deficient Mouse Livers"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-9535","authenticated-orcid":false,"given":"Hyun Ahm","family":"Sohn","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea"},{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7323-9114","authenticated-orcid":false,"given":"Anna","family":"Park","sequence":"additional","affiliation":[{"name":"Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minho","family":"Kang","sequence":"additional","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5663-5000","authenticated-orcid":false,"given":"Byoung-Ha","family":"Yoon","sequence":"additional","affiliation":[{"name":"Korea Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-5746","authenticated-orcid":false,"given":"Chul-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2224-7202","authenticated-orcid":false,"given":"Kyoung-Jin","family":"Oh","sequence":"additional","affiliation":[{"name":"Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cha Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong-Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1165-3173","authenticated-orcid":false,"given":"Han","family":"Koo","sequence":"additional","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyoung-Chin","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won Kee","family":"Yoon","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae-Sik","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daesoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7730-9466","authenticated-orcid":false,"given":"Kyung Chan","family":"Park","sequence":"additional","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4279-805X","authenticated-orcid":false,"given":"Young Il","family":"Yeom","sequence":"additional","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1096\/fj.09-151464","article-title":"The N-myc downstream regulated gene (NDRG) family: Diverse functions, multiple 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