Articles producció científica> Medicina i Cirurgia

Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease

  • Dades identificatives

    Identificador: imarina:5097887
    Autors:
    Hernández-Alvarez MISebastián DVives SIvanova SBartoccioni PKakimoto PPlana NVeiga SRHernández VVasconcelos NPeddinti GAdrover AJové MPamplona RGordaliza-Alaguero ICalvo ECabré NCastro RKuzmanic ABoutant MSala DHyotylainen TOreši? MFort JErrasti-Murugarren ERodrígues CMPOrozco MJoven JCantó CPalacin MFernández-Veledo SVendrell JZorzano A
    Resum:
    © 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.
  • Altres:

    Autor segons l'article: 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
    Departament: Medicina i Cirurgia
    Autor/s de la URV: Calvo Manso, Enrique / Fernandez Veledo, Sonia / Joven Maried, Jorge / Vendrell Ortega, Juan José
    Paraules clau: 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
    Resum: © 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.
    Àrees temàtiques: 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
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 00928674
    Adreça de correu electrònic de l'autor: enrique.calvo@urv.cat sonia.fernandez@urv.cat jorge.joven@urv.cat juanjose.vendrell@urv.cat
    Identificador de l'autor: 0000-0003-2906-3788 0000-0003-2749-4541 0000-0002-6994-6115
    Data d'alta del registre: 2024-10-26
    Versió de l'article dipositat: info:eu-repo/semantics/acceptedVersion
    Enllaç font 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 Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Cell. 177 (4): 881-895.e17
    Referència 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 de l'article: 10.1016/j.cell.2019.04.010
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2019
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Biochemistry & Molecular Biology,Biochemistry, Genetics and Molecular Biology (Miscellaneous),Cell Biology
    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
    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
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