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  • Hernández-Alvarez, María IsabelInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Institut Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain (författare)

Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease

  • Artikel/kapitelEngelska2019

Förlag, utgivningsår, omfång ...

  • Cell Press,2019
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:oru-74195
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-74195URI
  • https://doi.org/10.1016/j.cell.2019.04.010DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies:CONACYT, Mexico  MICINN Spain  Coordenacao de Aperfeicoamento do Pessoal de Nivel Superior (CAPES)  MINECO  SAF201675246R Generalitat de Catalunya (ICREA Academia)  2014SGR48  2017SGR696 INFLAMES (ISCIII) PIE-14/00045 CIBERDEM, ISCIII, INTERREG IV-B-SUDOE-FEDER (DIOMED)  SOE1/P1/E178 "la Caixa'' Foundation  Miguel Servet tenure-track program from the Fondo de Investigacion Sanitaria  CP10/00438  CPII16/00008 ERD  MINECO through the Centres of Excellence Severo Ochoa Award  CERCA Programme of the Generalitat de Catalunya 
  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Sebastián, DavidInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Departament de Bioquímica i Biomedicina Molecular, Facultat de Biología, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain (författare)
  • Vives, SaraInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain (författare)
  • Ivanova, SaškaInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Departament de Bioquímica i Biomedicina Molecular, Facultat de Biología, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain (författare)
  • Bartoccioni, PaolaInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; CIBERER, Instituto de Salud Carlos III, Madrid, Spain (författare)
  • Kakimoto, PamelaInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Departamento de Bioquímica, Instituto de Química, Universidad de São Paulo, São Paulo, Brazil (författare)
  • Plana, NataliaInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain (författare)
  • Veiga, Sónia R.Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Departamento de Bioquímica, Instituto de Química, Universidad de São Paulo, São Paulo, Brazil (författare)
  • Hernández, VanessaInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain (författare)
  • Vasconcelos, NunoInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain (författare)
  • Peddinti, GopalVTT Technical Research Center of Finland, Espoo, Finland (författare)
  • Adrover, AnnaInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain (författare)
  • Jové, MarionaDepartment of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain (författare)
  • Pamplona, ReinaldDepartment of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain (författare)
  • Gordaliza-Alaguero, IsabelInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Departament de Bioquímica i Biomedicina Molecular, Facultat de Biología, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain (författare)
  • Calvo, EnriqueInstitut Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain (författare)
  • Cabré, NoemíInstitut Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain; Universitat Rovira i Virgili, Department of Medicine and Surgery, Reus, Spain; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Reus, Spain (författare)
  • Castro, RuiResearch Institute for Medicines (iMed.ULisboa), and Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal (författare)
  • Kuzmanic, AntonijaInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain (författare)
  • Boutant, MarieNestlé Institute of Health Sciences SA, Lausanne, Switzerland (författare)
  • Sala, DavidDevelopment, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA (författare)
  • Hyötyläinen, Tuulia,1971-Örebro universitet,Institutionen för naturvetenskap och teknik(Swepub:oru)tihn (författare)
  • Oresic, Matej,1967-Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland(Swepub:oru)moc (författare)
  • Fort, JoanaInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Departament de Bioquímica i Biomedicina Molecular, Facultat de Biología, Barcelona, Spain; CIBERER, Instituto de Salud Carlos III, Madrid, Spain (författare)
  • Errasti-Murugarren, EkaitzInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain (författare)
  • Rodrígues, Cecilia M. P.Research Institute for Medicines (iMed.ULisboa), and Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal (författare)
  • Orozco, ModestoInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain (författare)
  • Joven, JorgeInstitut Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain; Universitat Rovira i Virgili, Department of Medicine and Surgery, Reus, Spain; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Reus, Spain (författare)
  • Cantó, CarlesNestlé Institute of Health Sciences SA, Lausanne, Switzerland (författare)
  • Palacin, ManuelInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Departament de Bioquímica i Biomedicina Molecular, Facultat de Biología, Barcelona, Spain; CIBERER, Instituto de Salud Carlos III, Madrid, Spain (författare)
  • Fernández-Veledo, SoniaInstitut Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain (författare)
  • Vendrell, JoanInstitut Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain; Universitat Rovira i Virgili, Tarragona, Spain (författare)
  • Zorzano, AntonioInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Departament de Bioquímica i Biomedicina Molecular, Facultat de Biología, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain (författare)
  • Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Institut Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, SpainInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Departament de Bioquímica i Biomedicina Molecular, Facultat de Biología, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Cell: Cell Press177:4, s. 881-895.e170092-86741097-4172

Internetlänk

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  • Cell (Sök värdpublikationen i LIBRIS)

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