Article (Scientific journals)
miR-873-5p targets mitochondrialGNMT-Complex II interface contributing tonon-alcoholic fatty liver disease
Fernández-Tussy, Pablo; Fernández-Ramos, David; Lopitz-Otsoa, Fernando et al.
2019In Molecular Metabolism
Peer reviewed
 

Files


Full Text
Fernandez-Tussy et al., 2019.pdf
Publisher postprint (3.06 MB)
Download

All documents in ORBilu are protected by a user license.

Send to



Details



Keywords :
microRNA; Metabolism; Mitochondria
Abstract :
[en] Objective:Non-alcoholic fatty liver disease (NAFLD) is a complex pathology in which several dysfunctions, including alterations in metabolicpathways, mitochondrial functionality and unbalanced lipid import/export, lead to lipid accumulation and progression to inflammation andfibrosis.The enzyme glycine N-methyltransferase (GNMT), the most important enzyme implicated in S-adenosylmethionine catabolism in the liver, isdownregulated during NAFLD progression. We have studied the mechanism involved in GNMT downregulation by its repressor microRNA miR-873-5p and the metabolic pathways affected in NAFLD as well as the benefit of recovery GNMT expression.Methods:miR-873-5p and GNMT expression were evaluated in liver biopsies of NAFLD/NASH patients. Differentin vitroandin vivoNAFLD murinemodels were used to assess miR-873-5p/GNMT involvement in fatty liver progression through targeting of the miR-873-5p as NAFLD therapy.Results:We describe a new function of GNMT as an essential regulator of Complex II activity in the electron transport chain in the mitochondria.In NAFLD, GNMT expression is controlled by miR-873-5p in the hepatocytes, leading to disruptions in mitochondrial functionality in a preclinicalmurine non-alcoholic steatohepatitis (NASH) model. Upregulation of miR-873-5p is shown in the liver of NAFLD/NASH patients, correlating withhepatic GNMT depletion. Importantly, NASH therapies based on anti-miR-873-5p resolve lipid accumulation, inflammation andfibrosis byenhancing fatty acidb-oxidation in the mitochondria. Therefore, miR-873-5p inhibitor emerges as a potential tool for NASH treatment.Conclusion:GNMT participates in the regulation of metabolic pathways and mitochondrial functionality through the regulation of Complex II activityin the electron transport chain. In NAFLD, GNMT is repressed by miR-873-5p and its targeting arises as a valuable therapeutic option for treatment.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Fernández-Tussy, Pablo;  CIC bioGUNE > Liver disease Laboratory
Fernández-Ramos, David;  CIC bioGUNE > Liver metabolism Laboratory
Lopitz-Otsoa, Fernando;  CIC bioGUNE > Liver metabolism Laboratory
Simón, Jorge;  CIC bioGUNE > Liver disease Laboratory
Barbier-Torres, Lucía;  CIC bioGUNE > Liver disease Laboratory
Gomez-Santos, Beatriz;  Universidad del País Vasco (España) = University of the Basque Country (Spain) - UPV > Department of Physiology, Faculty of Medicine and Nursing
Nuñez-Garcia, Maitane;  Universidad del País Vasco (España) = University of the Basque Country (Spain) - UPV > Department of Physiology, Faculty of Medicine and Nursing
Azkargorta, Mikel;  CICbioGUNE, CIBERehd > 2Proteomics Platform
Gutiérrez-de Juan, Virginia;  CIC bioGUNE > Metabolomics
Serrano-Macia, Marina;  CIC bioGUNE > Liver disease Laboratory
Rodríguez-Agudo, Rubén;  CIC bioGUNE > Liver disease Laboratory
Iruzubieta, Paula;  Marques de Valdecilla University Hospital > Gastroenterology and Hepatology Service
Anguita, Juan;  Ikerbasque, Basque Foundation for Science > Macrophage and Tick Vaccine Laboratory, CIC bioGUNE
Castro, Rui Eduardo;  Universidade de Lisboa > Faculty of Pharmacy
Champagne, Devin;  University of Vermont College of Medicine > Department of Medicine
Rincón, Mercedes;  University of Vermont, College of Medicine > Department of Medicine
Elortza, Felix;  CIC bioGUNE > Proteomics Platform
Arslanow, Anita;  Saarland University Medical Center > Department of Medicine II
Krawczyk, Marcin;  Saarland University Medical Center > Department of Medicine II
Lammert, Frank;  Saarland University Medical Center > Department of Decine II
KIRCHMEYER, Mélanie ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
BEHRMANN, Iris ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Crespo, Javier;  University Hospital Marques de Valdecilla > Gastroenterology and Hepatology Service
Lu, Shelly;  Cedars-Sinai Medical Center, Los Angeles, CA, USA > Division of Digestive and Liver Diseases
Mato, José;  CIC bioGUNE > Liver Metabolism
Varela-Rey, Marta;  CIC bioGUNE > Liver disease
Aspichueta, Patricia;  Universidad del País Vasco (España) = University of the Basque Country (Spain) - UPV > Faculty of Medicine and Dentistry
Cardoso Delgado, Teresa;  CIC bioGUNE > Liver disease
Martinez_Chantar, Maria;  Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) > Liver disease Laboratory, Liver metabolism Laboratory, CIC bioGUNE
More authors (19 more) Less
External co-authors :
yes
Language :
English
Title :
miR-873-5p targets mitochondrialGNMT-Complex II interface contributing tonon-alcoholic fatty liver disease
Publication date :
16 August 2019
Journal title :
Molecular Metabolism
Peer reviewed :
Peer reviewed
Available on ORBilu :
since 20 February 2020

Statistics


Number of views
87 (1 by Unilu)
Number of downloads
78 (0 by Unilu)

Scopus citations®
 
34
Scopus citations®
without self-citations
29
OpenCitations
 
20
WoS citations
 
32

Bibliography


Similar publications



Contact ORBilu