Key discovery in cellular adaptation to fasting

A national and international collaborative study led by the Liver Disease laboratory of Dr. Malu Martínez-Chantar (CIC bioGUNE – member of BRTA -, CIBER of Hepatic and Digestive Diseases (CIBEREHD) and by the Gene Regulatory Control in Disease team of the Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) directed by Dr. Marta Varela, has identified the levels of the methyl group donor SAMe (S-adenosylmethionine) as a novel molecular mechanism underlying the physiological response of fasting and cellular adaptation to nutritional stress.

The study demonstrated a significant decrease in liver SAMe levels during fasting, which acts as a critical intracellular sensor. This phenomenon activates the interaction between the endoplasmic reticulum (ER) and mitochondria, as well as β-oxidation, a vital process for lipid metabolism in the liver. These results provide a new perspective on how the organism adapts and responds to fasting conditions.

In addition, researchers have also shown that the local synthesis of SAMe in mitochondrial membranes (MAMs) plays a protective role by reducing liver damage. This discovery highlights the importance of the precise regulation of SAMe levels in liver cells during fasting and provides further insight into the molecular mechanisms involved in the adaptive response to nutritional stress conditions.

The implications of this research could have significant implications in the design of therapeutic approaches for diseases related to hepatic metabolism and nutritional regulation.

Reference: Alba Capelo-Diz, Sofía Lachiondo-Ortega, David Fernández-Ramos, Jorge Cañas-Martin, Naroa Goikoetxea-Usandizaga, Marina Serrano-Maciá, Maria J. González-Rellan, Laura Mosca, Joan Blazquez-Vicens, Alberto Tinahones-Ruano, Marcos F. Fondevila, Mason Buyan, Teresa C. Delgado, Virginia Gutierrez de Juan, Paula Ayuso-García, Alejandro Sánchez-Rueda, Sergio Velasco-Avilés, Héctor Fernández-Susavila, Cristina Riobello-Suárez, Bartlomiej Dziechciarz, Cristina Montiel-Duarte, Fernando Lopitz-Otsoa, Maider Bizkarguenaga, Jon Bilbao-García, Ganeko Bernardo-Seisdedos, Ana Senra, Mario Soriano-Navarro, Oscar Millet, Ángel Díaz-Lagares, Ana B. Crujeiras, Aida Bao-Caamano, Diana Cabrera, Sebastiaan van Liempd, Miguel Tamayo-Carro, Luigi Borzacchiello, Beatriz Gomez-Santos, Xabier Buqué, Diego Sáenz de Urturi, Francisco González-Romero, Jorge Simon, Rubén Rodríguez-Agudo, Asier Ruiz, Carlos Matute, Daniel Beiroa, Juan M. Falcon-Perez, Patricia Aspichueta, Juan Rodríguez-Cuesta, Marina Porcelli, María A. Pajares, Cristina Ameneiro, Miguel Fidalgo, Ana M. Aransay, Tomas Lama-Díaz, Miguel G. Blanco, Miguel López, Ricardo Villa-Bellosta, Timo D. Müller, Rubén Nogueiras, Ashwin Woodhoo, María Luz Martínez-Chantar,* and Marta Varela-Rey,**.

Cell Metabolism. DOI: 10.1016/j.cmet.2023.07.002

About CIC bioGUNE

The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.

About CIBEREHD

The Consortium of Biomedical Network Research Centres (CIBER) is a public research consortium created on the initiative of the Instituto de Salud Carlos III / Carlos III Health Institute, of the Ministry of Science and Innovation, to further research of excellence in biomedicine and health sciences conducted within the National Health System and the Science and Technology System. The scientific programme of the CIBER is organised around 13 thematic areas of research, including the area of Liver Diseases (CIBEREHD) and Diabetes and Associated Metabolic Diseases (CIBERDEM).

About CiMUS

The Singular Centre for Research in Molecular Medicine and Chronic Diseases is a research centre located in Santiago de Compostela, which aims to promote the development of interdisciplinary research in the field of biomedical sciences, through internal interaction and collaboration and with relevant national and international groups.

About BRTA

BRTA is an alliance of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 12 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Lortek, Neiker, Tecnalia, Tekniker and Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.

With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centres, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.

BRTA has a workforce of 3,500 professionals, executes 22% of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.