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Pathophysiology of Mitochondrial Biogenesis


The Research Group in Pathophysiology of Mitochondrial Biogenesis belongs to the i+12 Institute because of its long-standing cooperation with the research group led by Dr. Miguel Ángel Martín Casanueva.

This collaboration began at the end of the nineties, together with the research group led by Dr. Joaquín Arenas, with the common aim to study the pathophysiology of mitochondrial diseases. Each group contributed their own experience in their complementary profiles: clinical (Joaquín Arenas) and basic (Rafael Garesse). Our joint work has been reflected in the financing of numerous projects of Spanish National Plans, published articles with shared authorship, and participation in cooperative thematic research networks. We currently collaborate within the context of the i+12, Institute of the Center for Network Biomedical Research in Rare Diseases (CIBERER, Centro de Investigación Biomédica en Red sobre Enfermedades Raras) and the RAREGENOMICS-CM consortium (B2017/BMD-3721), both of which integrate the two groups.

Our combined group is currently comprised by eight members: four senior researchers (two of whom are currently reconciling their research activity in the laboratory with positions of responsibility as the chancellor of the Universidad Autónoma de Madrid and the subdirector of the Biochemistry Department of this university, respectively), a contracted researcher from the CIBERER with extensive experience, two funded predoctoral students and a laboratory technician. In addition, by being immersed both in the academic environment of the University and a research environment (CIBER, RAREGENOMICS-CM, and other institutions we interact with, such as the Spanish National Center for Cancer Research [CNIO, Centro Nacional de Investigaciones Oncológicas], the Spanish National Center for Cardiovascular Research [CNIC, Centro Naccional de Investigaciones Cardiovasculares], the Spanish National Center for Biotechnology [CNB, Centro Nacional de Biotecnología], the Spanish Center for Molecular Biology [CBM, Centro de Biología Molecular], etc.) we believe that we enjoy a fortunate position that allows us to enrich our current abilities and to cooperate with other working groups belonging to the Spanish national healthcare system (especially the i+12 Institute).

The main line of research of our group is the study of the mitochondrial function in both physiological and pathological situations, particularly of its involvement in a wide range of rare diseases. Our focus of interest is twofold: we aim to understand the underlying molecular mechanisms of these diseases and to attempt to develop therapeutic options that may alleviate a class of diseases that have been virtually untreatable to date.

The general objectives of our group are the following:

  1. To contribute to the current knowledge about the role of mitochondria in human diseases.
  2. To contribute to the discovery of the genetic, biochemical and molecular bases of mitochondrial diseases.
  3. To contribute to the development of means aimed at alleviating the consequences of this type of diseases at both a strategic and technological level.

The specific objectives of our group are the following:

  1. To identify, by means of various experimental approaches, new genes involved in the oxidative phosphorylation (OXPHOS) process that may be potentially responsible for mitochondrial diseases (MD).
  2. To functionally characterize these new genes in model cellular and animal systems through the implementation of genome editing technology CRISPR/Cas.
  3. On the basis of the results of the previous study, to generate a next-generation sequencing (NGS) gene panel in an attempt to identify potential mutations in patients with multiple sclerosis (MS) without a genetic-molecular diagnosis.
  4. To create animal models (Drosophila sp.) of MS to further our current knowledge in the molecular mechanisms involved in the pathological manifestation of the genetic defect.
  5. To generate induced pluripotent stem cells (iPSCs) from fibroblasts of patients with MS resulting from mutations in both mitochondrial and nuclear genes.
  6. To characterize the biochemical and phenotypic consequences of mutations responsible for MS in different cell types that result in the targeted differentiation of iPSCs.
  7. To study the dependence of the processes of fibroblast reprogramming to iPSCs and fibroblast differentiation to the cell types of interest on mitochondrial function.
  8. To attempt to develop a system for the in vivo insertion of exogenous DNA into mitochondria of human cells.

In the context of the RAREGENOMICS (RAREGENOMICS-CM) network, this group is interested in participating in the creation of a collaborative network focused on researching the underlying physiopathogenic mechanisms of mitochondrial diseases that may allow for identifying new genes involved in these disorders and potential treatments by making use of the possibilities offered by induced pluripotent stem cells.