Autor según el artículo: Hernández-Alvarez MI; Sebastián D; Vives S; Ivanova S; Bartoccioni P; Kakimoto P; Plana N; Veiga SR; Hernández V; Vasconcelos N; Peddinti G; Adrover A; Jové M; Pamplona R; Gordaliza-Alaguero I; Calvo E; Cabré N; Castro R; Kuzmanic A; Boutant M; Sala D; Hyotylainen T; Oreši? M; Fort J; Errasti-Murugarren E; Rodrígues CMP; Orozco M; Joven J; Cantó C; Palacin M; Fernández-Veledo S; Vendrell J; Zorzano A
Departamento: Medicina i Cirurgia
Autor/es de la URV: Calvo Manso, Enrique / Fernandez Veledo, Sonia / Joven Maried, Jorge / Vendrell Ortega, Juan José
Palabras clave: Triglycerides Triacylglycerol Signal transduction Protein transport Protein lipid interaction Protein function Protein expression Protein deficiency Protein binding Priority journal Primary cell culture Physiology Phospholipid transfer Phospholipid synthesis Phosphatidylserines Phosphatidylserine Phosphatidylethanolamine Phenotype Pathology Nonhuman Nonalcoholic fatty liver Non-alcoholic fatty liver disease Nash Mouse model Mouse Mitofusin 2 Mitochondrion Mitochondrial proteins Mitochondrial protein Mitochondria Mice, inbred c57bl Mice Mfn2 protein, human Mfn2 Metabolism Mams Male Liver protection Liver fibrosis Liver diseases Liver disease Liver cell Liver cancer Liver biopsy Liver Lipid transport Lipid metabolism Inflammation Hypertriglyceridemia Humans Human tissue Human Hepatocytes Hepatitis Guanosine triphosphatase Gtp phosphohydrolases Endoplasmic reticulum stress Endoplasmic reticulum Disease models, animal Disease model Controlled study Cell growth C57bl mouse Article Apoptosis Animals Animal tissue Animal model Animal experiment Animal
Resumen: © 2019 Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.
Áreas temáticas: Odontología Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar General medicine General biochemistry,genetics and molecular biology Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cell biology Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Biochemistry & molecular biology
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 00928674
Direcció de correo del autor: enrique.calvo@urv.cat sonia.fernandez@urv.cat jorge.joven@urv.cat jvortega@iispv.cat
Identificador del autor: 0000-0003-2906-3788 0000-0003-2749-4541 0000-0002-6994-6115
Fecha de alta del registro: 2024-11-09
Versión del articulo depositado: info:eu-repo/semantics/acceptedVersion
Enlace a la fuente original: https://www.cell.com/cell/fulltext/S0092-8674(19)30396-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867419303964%3Fshowall%3Dtrue
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Cell. 177 (4): 881-895.e17
Referencia de l'ítem segons les normes APA: Hernández-Alvarez MI; Sebastián D; Vives S; Ivanova S; Bartoccioni P; Kakimoto P; Plana N; Veiga SR; Hernández V; Vasconcelos N; Peddinti G; Adrover A (2019). Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease. Cell, 177(4), 881-895.e17. DOI: 10.1016/j.cell.2019.04.010
DOI del artículo: 10.1016/j.cell.2019.04.010
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2019
Tipo de publicación: Journal Publications
Repositori URV