Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Choi, S; Dong, B; Lin, CJ; Heo, MJ; Kim, KH; Sun, Z; Wagner, M; Putluri, N; Suh, JM; Wang, MC; Moore, DD.
Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function in Mouse Hepatocytes.
Hepatology. 2020; 71(3):1055-1069 Doi: 10.1002/hep.30884 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

Wagner Martin

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Abstract:

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). 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. A PEMT-LRH-1 axis regulates mitochondrial biogenesis and beta-oxidation in hepatocytes. © 2019 by the American Association for the Study of Liver Diseases.

Find related publications in this database (using NLM MeSH Indexing)

Animals -

Hep G2 Cells -

Hepatocytes - metabolism

Humans -

Male -

Mice -

Mitochondria - physiology

Oxidation-Reduction -

Phosphatidylethanolamine N-Methyltransferase - physiology

Receptors, Cytoplasmic and Nuclear - physiology

S-Adenosylmethionine - metabolism

S-Adenosylmethionine - pharmacology

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