ArticleHepatology (Baltimore, Md.)2020
Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function in Mouse Hepatocytes.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- From hepatic to hematopoietic: LRH-1's expanding cellular repertoire to the immune system.The FEBS journal · 2026Review
- Article
- LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype.Clinical and translational medicine · 2024Article
- Regulation of Betaine Homocysteine Methyltransferase by Liver Receptor Homolog-1 in the Methionine Cycle.Molecular and cellular biology · 2024Article
- Mitochondrial GpC and CpG DNA Hypermethylation Cause Metabolic Stress-Induced Mitophagy and Cholestophagy.International journal of molecular sciences · 2023Article
- LRH-1 activation alleviates diabetes-induced podocyte injury by promoting GLS2-mediated glutaminolysis.Cell proliferation · 2023Article
- Phosphatidylethanolamine N-methyltransferase: from Functions to Diseases.Aging and disease · 2023Review
- LRH-1 induces hepatoprotective nonessential amino acids in response to acute liver injury.The Journal of clinical investigation · 2023Article
- A phospholipid mimetic targeting LRH-1 ameliorates colitis.Cell chemical biology · 2022Article
- Differential Modulation of Nuclear Receptor LRH-1 through Targeting Buried and Surface Regions of the Binding Pocket.Journal of medicinal chemistry · 2022Article
- Hepatic stellate cell reprogramming via exosome-mediated CRISPR/dCas9-VP64 delivery.Drug delivery · 2021Article
- Article
- Perilipin 5 is a novel target of nuclear receptor LRH-1 to regulate hepatic triglycerides metabolism.BMB reports · 2021Article
- Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia.Communications biology · 2021Article
- Enantiomer-specific activities of an LRH-1 and SF-1 dual agonist.Scientific reports · 2020Article
- Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication.Signal transduction and targeted therapy · 2020Review
- GATA6 enhances the stemness of human colon cancer cells by creating a metabolic symbiosis through upregulating LRH-1 expression.Molecular oncology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
aimsLiver 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
resultsHere, 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.
conclusionsA PEMT-LRH-1 axis regulates mitochondrial biogenesis and beta-oxidation in hepatocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.