May 2019

Researchers at iMed.ULisboa participate in study identifying a key mitochondrial protein that protects against non-alcoholic fatty liver disease

A global epidemy of obesity and metabolic syndrome, mainly fueled by the ingestion of excessive calories and sedentary lifestyles, is contributing for the increased worldwide incidence of non-alcoholic fatty liver disease (NAFLD). This liver disease encompasses several severity stages, ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis, cirrhosis and, eventually, hepatocellular carcinoma.

No pharmacotherapy is currently available for treating NAFLD. In this regard, Rui Castro and Cecília Rodrigues, from iMed.ULisboa’s Cellular Function and Therapeutic Targeting Group, participated in a study led by Antonio Zorzano from IRB Barcelona, showing that mitofusion-2 protein confers protection against NAFLD, thus embodying an attractive target for therapeutic intervention.

The study, just published in the journal Cell, illustrates that mitofusin-2 protein is reduced in NAFLD animal models and patients, leading to a reduced transfer of phosphatidylserine from endoplasmic reticulum to mitochondria and, as a consequence, development of a NASH-like phenotype and liver cancer.

Both groups continue to collaborate on trying to identify and characterize novel molecular modulators of mitofusin-2, aiming at its targeting in the NAFLD clinical context.

Reference 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, Boutant M, Sala D, Hyotylainen T, Orešič M, Fort J, Errasti-Murugarren E, Rodrigues CMP, Orozco M, Joven J, Cantó C, Palacin M, Fernández-Veledo S, Vendrell J, Zorzano A.

Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease.

Cell (2019) DOI: https://doi.org/10.1016/j.cell.2019.04.010