DC Field | Value | Language |
---|---|---|
dc.contributor.author | Choi, Sungwoo | ko |
dc.contributor.author | Dong, Bingning | ko |
dc.contributor.author | Lin, Chih-Chun Janet | ko |
dc.contributor.author | Heo, Mi Jeong | ko |
dc.contributor.author | Kim, Kang Ho | ko |
dc.contributor.author | Sun, Zhen | ko |
dc.contributor.author | Wagner, Martin | ko |
dc.contributor.author | Putluri, Nagireddy | ko |
dc.contributor.author | Suh, Jae Myoung | ko |
dc.contributor.author | Wang, Meng C. | ko |
dc.contributor.author | Moore, David D. | ko |
dc.date.accessioned | 2020-10-21T00:55:38Z | - |
dc.date.available | 2020-10-21T00:55:38Z | - |
dc.date.created | 2020-01-07 | - |
dc.date.created | 2020-01-07 | - |
dc.date.created | 2020-01-07 | - |
dc.date.issued | 2020-03 | - |
dc.identifier.citation | HEPATOLOGY, v.71, no.3, pp.1055 - 1069 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | http://hdl.handle.net/10203/276737 | - |
dc.description.abstract | Background and Aims Liver receptor homolog-1 (LRH-1; NR5A2) is a nuclear receptor that regulates metabolic homeostasis in the liver. Previous studies identified phosphatidylcholines as potential endogenous agonist ligands for LRH-1. In the liver, distinct subsets of phosphatidylcholine species are generated by two different pathways: choline addition to phosphatidic acid through the Kennedy pathway and trimethylation of phosphatidylethanolamine through phosphatidylethanolamine N-methyl transferase (PEMT). Approach and Results Here, we report that a PEMT-LRH-1 pathway specifically couples methyl metabolism and mitochondrial activities in hepatocytes. We show that the loss of Lrh-1 reduces mitochondrial number, basal respiration, beta-oxidation, and adenosine triphosphate production in hepatocytes and decreases expression of mitochondrial biogenesis and beta-oxidation genes. In contrast, activation of LRH-1 by its phosphatidylcholine agonists exerts opposite effects. While disruption of the Kennedy pathway does not affect the LRH-1-mediated regulation of mitochondrial activities, genetic or pharmaceutical inhibition of the PEMT pathway recapitulates the effects of Lrh-1 knockdown on mitochondria. Furthermore, we show that S-adenosyl methionine, a cofactor required for PEMT, is sufficient to induce Lrh-1 transactivation and consequently mitochondrial biogenesis. Conclusions A PEMT-LRH-1 axis regulates mitochondrial biogenesis and beta-oxidation in hepatocytes. | - |
dc.language | English | - |
dc.publisher | WILEY | - |
dc.title | Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function in Mouse Hepatocytes | - |
dc.type | Article | - |
dc.identifier.wosid | 000504014200001 | - |
dc.identifier.scopusid | 2-s2.0-85076933078 | - |
dc.type.rims | ART | - |
dc.citation.volume | 71 | - |
dc.citation.issue | 3 | - |
dc.citation.beginningpage | 1055 | - |
dc.citation.endingpage | 1069 | - |
dc.citation.publicationname | HEPATOLOGY | - |
dc.identifier.doi | 10.1002/hep.30884 | - |
dc.contributor.localauthor | Suh, Jae Myoung | - |
dc.contributor.nonIdAuthor | Choi, Sungwoo | - |
dc.contributor.nonIdAuthor | Dong, Bingning | - |
dc.contributor.nonIdAuthor | Lin, Chih-Chun Janet | - |
dc.contributor.nonIdAuthor | Heo, Mi Jeong | - |
dc.contributor.nonIdAuthor | Kim, Kang Ho | - |
dc.contributor.nonIdAuthor | Sun, Zhen | - |
dc.contributor.nonIdAuthor | Wagner, Martin | - |
dc.contributor.nonIdAuthor | Putluri, Nagireddy | - |
dc.contributor.nonIdAuthor | Wang, Meng C. | - |
dc.contributor.nonIdAuthor | Moore, David D. | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | PHOSPHATIDYLETHANOLAMINE-N-METHYLTRANSFERASE | - |
dc.subject.keywordPlus | PLASMA HIGH-DENSITY | - |
dc.subject.keywordPlus | HORMONE-RECEPTOR | - |
dc.subject.keywordPlus | PHOSPHATIDYLCHOLINE | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | DELETION | - |
dc.subject.keywordPlus | REVEALS | - |
dc.subject.keywordPlus | DOMAIN | - |
dc.subject.keywordPlus | ALPHA | - |
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