Miniatura

Fitxers

703669.pdf (3.99 MB)

Tipus de document

Article

Versió

Versió acceptada

Data de publicació

2019-05-02

Llicència de publicació

cc-by-nc-nd (c) Elsevier, 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/171647

Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1016/j.cell.2019.04.010

Resum

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.

Matèries

Malalties del fetge, Proteïnes de membrana, Mitocondris

Matèries (anglès)

Liver diseases, Membrane proteins, Mitochondria

Citació

Col·leccions

Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

HERNÁNDEZ-ALVAREZ, María isabel, SEBASTIÁN MUÑOZ, David, VIVES, Sara, IVANOVA, Saška, BARTOCCIONI, Paola, KAKIMOTO, Pamela, PLANA, Natalia, VEIGA, Sonia rosa pereira da, 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. Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease. _Cell_. 2019. Vol. 177, núm. 4, pàgs. 881-895. [consulta: 21 de gener de 2026]. ISSN: 0092-8674. [Disponible a: https://hdl.handle.net/2445/171647]

Exportar metadades

JSON - METS

Compartir registre