Mithocondrial Regulation of Cell Death


José Carlos Fernández-Checa

Research Professor
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The laboratory of “Mitochondrial Regulation of Cell Death”, directed by Jose Carlos Fernandez-Checa, was created in 1992 upon the incorporation of Jose C. Fernandez-Checa and Carmen Garcia Ruiz from the University of Los Angeles (UCLA) and the University of Southern California (USC), where they worked for almost 10 years as Faculty, to the University of Barcelona and the Liver Unit of the Hospital Clinic i Provincial of Barcelona. The laboratory is nowadays based at the Institute of Biomedical Research of Barcelona from the Spanish Research Council (IIBB-CSIC) and at the “Instituto de Investigaciones Biomédicas Agustí Pi i Sunyer” (IDIBAPS) in Barcelona. Throughout these 30 years, many scientists have contributed with great effort and dedication to an extraordinary academic production both in magnitude and in quality.There have been many collaborators who, with their commitment and dedication, have contributed to a first-rate academic production. A large number of pre and postdoctoral students, both national and international, have been trained and the laboratory has directed 32 doctoral theses, some recognized with the Extraordinary Prize and others with International Mention. Many of them now lead their own research teams, evidencing the great educational work carried out by the group.

The work conducted in the group throughout these years has been highly effective, having contributed to the more than 70 joint publications published in high-impact journals. Our group that actively participates and attends international and national conferences to share our work and establish links with other researchers. It is a highly internationalized group, reflected by the extensive collaborations it maintains with various centers and universities throughout different countries: Prof. M Karin (University of California, San Diego, USA), Prof. Neil Kaplowitz ( University of Southern California, Los Angeles, USA), Prof. M Grompe (Oregon Stem Cell Centre, Oregon, USA), Prof. S Zalungo (Pontifical Catholic University of Chile, Chile), Prof. MA Avila (Center for Applied Medical Research University of Navarra, Spain), Prof. JM Mato (CIC bioGUNE, Derio, Spain), Prof. C Gutiérrez (Metropolitan University of Mexico), Prof. I. Bergheim (University of Vienna), Prof. M Sorice (Sapienza University of Rome, Rome, Italy), and a long etcetera.

In parallel, the group participates in various scientific outreach activities and actively contributes to society by participating in public engagement activities such as "Science Week", seminars, or master classes for high school students.



The overarching goal of the “Mitochondrial Regulation of Cell Death” laboratory is to expand the knowledge of the biological mechanisms that modulate mitochondrial function and how this modulation contributes to hepatic and neurodegenerative diseases with the aim of improving current medical practice, from diagnosis to treatment, of such disorders.

The group focuses on the study of the contribution of lipids, such as cholesterol, in regulating the function of the mitochondria. Healthy mitochondrial function is essential for cell survival. That is why the laboratory investigates how variations in mitochondrial activity contributes to the development of liver diseases, such as steatohepatitis, and its progression towards liver cancer, and neurodegenerative diseases such as Alzheimer's (AD) or Niemann Pick Type C (NPC), with the aim of identifying new therapeutic targets and design better and more specific drugs.

The laboratory uses cellular and mice models to investigate the cellular and molecular bases related to the progression of liver disease and neurodegeneration and it applies therapeutic interventions to improve the final outcome of the disorders. It is equipped with genetically modified mice that allow the study of different proteins in specific cell-types. In addition, an innovative mouse model transplanted with human liver cells has been generated in the group, which enables the realization of studies within a scenario that is more similar to that of the patient.

Using such approaches, one of the group’s most important discoveries has been how mitochondrial cholesterol influences the development of liver diseases and neuronal function. The various lines of research in the laboratory are focused on improving our understanding about the biological mechanisms controlling these conditions in different pathological situations, in order to design new drugs or to reuse existing ones for treatment.


Lines of research

  • Regulation of oxidative stress of sphingolipids and mitochondria during cell death

Sphingolipid metabolism is important to regulate the machinery of cell death and releases the molecular culprits involved in the execution of this process in its various environments, which include apoptosis, necrosis, and necroapoptosis.

  • Mechanisms responsible for the transport of cholesterol to the mitochondria and its role in non-alcoholic steatohepatitis (NASH), hepatocellular carcinoma and neurodegenerative diseases

Since cholesterol is an important factor that determines the structural properties of lipid bilayers, one of our goals was to understand the mechanisms underlying intracellular cholesterol trafficking in mitochondria and its impact on liver and neurodegenerative diseases (such as Alzheimer's or Niemann Pick disease) by generating genetic models deleting the StARD1 protein, a mitochondrial cholesterol transporter protein, in specific cells.

  •  Translational Research in Nonalcoholic Steatohepatitis (NASH): Development of NASH in a Humanized Mouse Model to Identify Potential Targets in Human NASH

Since the biology of mice and humans is different, we have developed a mouse model with a humanized liver, which can increase the translational importance of experimental research as it allows carrying out studies in a more similar setting to that of patients.

  • Contribution of sphingolipids and cholesterol to acute liver failure

To determine the role of mutual regulation between sphingolipids and cholesterol in lysosomes and mitochondrial turnover in the regulation of drug-induced liver injury.

  • Study of the role of mitochondrial cholesterol and glycosphingolipids in liver fibrosis. Reciprocal regulation between HIF1a and StARD1 in steatohepatitis and hepatocellular carcinoma

Our objective is to study the impact of mitochondrial cholesterol and glycosphingolipids on the stabilization/activation of HIF1a, its impact on the progression to alcoholic and non-alcoholic steatohepatitis (ASH/NASH) and on the progression of NASH to hepatocellular carcinoma.

  • Study of the mitochondrial reticulum-cholesterol stress axis in insulin resistance associated with obesity and comorbidities

Our purpose is to understand the impact of mitochondrial cholesterol on adipose tissue and muscle, and its interaction on insulin resistance and nonalcoholic steatohepatitis.

  •  Role of lysosomal proteases during tissue remodeling and regeneration in liver and kidney injuries

This line of research focuses on the identification of new therapeutic targets for the treatment of liver and kidney diseases by studying the cellular and molecular pathways involved in the progression of the disease, with special emphasis on the biology of proteases.


Past lab members:

Albert Morales Muñoz

Merce Miranda

  • Professional development: Medical writer

Anna Colell

Esther Ardite

  • Professional development: Science teacher at “Institut Bonanova”

Monserrat Marí

Raquel Paris:

  • Professional development: Product Manager at Alere Health LLC, Barcelona

Mº del Carmen Blasco

  • Professional development: Clinical Research Project Manager at Grifols, VC Clinical Operations Department

Josep María Lluïs Duquez

  • Professional development: Senior CRA at PRA Health Sciencies, Sweden

Roberto Alejandro Rabinovich

  • Professional development: LAS in Respiratory Medicine at the Royal Infirmary of Edinburgh. Honorary Contract with NHS

Olga Coll

  • Professional development: postdoctoral researcher at the “Gene Regulation, stem cells and cancer group” in the Centre for Genomic Regulation (CRG) in Barcelona

Luis Enrique Gómez-Quiroz

  • Professional development: Principal Investigator at the “Área de Medicina Experimental y Traslacional, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico”

Francisco Caballero

  • Professional development: Principal Consultant at CamBio LLC

Joan Montero Boronat

  • Professional development: Ramón y Cajal Senior Resarcher at the “Nanobioengineering” group at the Institute for Bioengineering of Catalonia (IBEC)

Laura Llacuna Duran

  • Professional development: Health Coach

Anna Moles

  • Professional development: Científico Titular IIBB-CSIC.

Anna Fernández Fernández

  • Professional development: Bioassay Scientist in Analytical Development Department at mAbxience (León)



      Nuria Tarrats Font

      • Professional development: Researcher at “DEBRA Butterfly Children charity (NGO DEBRA, Spain) research team

      Raquel Fucho

      • Professional development: Senior Biotech Coordinator at BCNatal Fetal Research Center. Hospital Sant Joan de Déu, Barcelona

        Milica Stefanovic

        • Professional development: Radiation oncologist at the Catalan Institute of Oncology (ICO)

        Cristina Bárcena

        • Professional development: Collaborator at National Institute of Physical Education (INEFC), Department of Physiology, Barcelona

        Laura Martínez Gili

        • Professional development: Postdoctoral Research Fellow at the “BRC Gut Healt Theme” at the Imperial College London

        Elisabet Barbero Camps

        • Professional development: science teacher at l'Institut de Santa Coloma de Farners, Girona (Catalunya)

        Anna Baulies Domenech

        • Professional development: 2015-current: Postdoctoral Researcher at the “Stem cell and Cancer biology” laboratory at the Francis Crick Institute London, United Kingdom

        Natalia Nuño Lambarri

        • Professional development: Basic Researcher of the Translational Research Unit at the Medica Sur Clinic & Foundation (México)

        Sandra Torres Núñez

        • Professional development: 2019-current: Postdoctoral Scientist at University Clinic Frankfurt, in the Group of “Translational Hepatology” established by Prof. Dr. MD. Jonel Trebicka within the Department of Internal Medicine I.

        Mª Carmen Vallejo

        • Professional development: science teacher at I.E.S. Santo Domingo High School (Almería, Spain).

        Cristina Alarcón

        • Professional development: postdoctoral research scientist (H2020 project) at the Immulogy service of Hospital Universitario Virgen de la Arrixaca (Murcia, Spain).

        David Robles

        • Professional development: 2020-2021: science teacher at the departament d'educació (Catalunya, Spain).

        Estel Solsona i Vilarrasa

        • Professional development: 2021-current: Postdoctoral Researcher at The Francis Crick Institute at “p53 and Metabolism” laboratory (Prof. Karen Vousden).

        Naroa Insausti

        • Professional development: Scientific staff at Viralgen CDMO in the Basque Country, Spain



        Prof. N Kaplowitz; University of Southern California, Los Angeles. USA


        Prof. H Tsukamoto; University of Southern California, Los Angeles. USA


        Prof. MA Avila; Centro de Investigación Médica Aplicada de la Universidad de Navarra, España


        Prof. JM Mato;  CIC bioGUNE, Derio, España


        Prof. M Grompe; Oregon Stem Cell Centre, Oregon. USA


        Prof. R Bataller; Pittsburg Liver Research Centre


        Dr. J Caballeria; Hospital Clinic, Barcelona, España



        Prof. M Sorice; Sapienza University of Rome, Roma, Italia


        Prof. S Zalungo; Pontifical Catholic University of Chile, Chile


        Prof. C Gutierrez; Universidad Metropolitana de México



        Prof. I. Bergheim; University of Vienna




        The research of the group is funded through competitive public and private calls hold by entities like:

        NIAAA - National Institute on Alcohol Abuse and Alcoholism

        Together Strong NPC Foundation-USA

        Fundació La Marató de TV3

        BBVA - Banco Bilbao Vizcaya Argentaria

        CIBEREHD – Centro de Investigación Biomédica en Red-Enfermedades Hepáticas y Digestivas

        AGAUR - Agencia de Gestión de Ayudas Universitarias y de Investigación

        Spanish Ministry of Economy and Competitiveness – Ministerio de Economía y Competitividad

        Spanish Ministry of Health – Ministerio de Sanidad

        Spanish Ministry of Science and Innovation – Ministerio de Ciencia e Innovación

        COST Action (European Cooperation in Science and Technology)

        National Insititute of Health (USA)