دورية أكاديمية
Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease
| العنوان: | Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease |
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| المؤلفون: | Hernández-Alvarez, María Isabel, Sebastián Muñoz, David, Vives, Sara, Ivanova, Saska, Bartoccioni, Paola, Kakimoto, Pamela, Plana, Natalia, Veiga, Sonia R., Hernandez, Vanessa, Vasconcelos, Nuno, Peddinti, Gopal, Adrover, Anna, Jove, Mariona, Pamplona, Reinald, Gordaliza-Alaguero, Isabel, Calvo, Enrique, Cabre, Noemí, Castro, Rui, Kuzmanic, Antonija, Boutant, Marie, Sala, David, Hyotylainen, Tuulia, Oresic, Matej, Fort i Baixeras, Joana, Errasti-Murugarren, Ekaitz, Rodrigues, CMP., Orozco López, Modesto, Joven, Jorge, Cantó, Carles, Palacín Prieto, Manuel, Fernandez-Veledo, Sonia, Vendrell, Joan, Zorzano Olarte, Antonio |
| المصدر: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2019 |
| المجموعة: | Dipòsit Digital de la Universitat de Barcelona |
| مصطلحات موضوعية: | Malalties del fetge, Proteïnes de membrana, Mitocondris, Liver diseases, Membrane proteins, Mitochondria |
| الوصف: | 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 nonalcoholic 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 33 p.; application/pdf |
| اللغة: | English |
| تدمد: | 0092-8674 |
| العلاقة: | Versió postprint del document publicat a: https://doi.org/10.1016/j.cell.2019.04.010Test; Cell, 2019, vol. 177, num. 4, p. 881-895; https://doi.org/10.1016/j.cell.2019.04.010Test; http://hdl.handle.net/2445/171647Test; 703669 |
| الإتاحة: | https://doi.org/10.1016/j.cell.2019.04.010Test http://hdl.handle.net/2445/171647Test |
| حقوق: | cc-by-nc-nd (c) Elsevier, 2019 ; http://creativecommons.org/licenses/by-nc-nd/3.0/esTest ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.A4A43A7 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00928674 |
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