Mitochondria play a crucial role in cellular physiology, as they are involved in a variety of processes such as lipid metabolism, calcium buffering, apoptosis, the assembly of iron-sulphur clusters or the biosynthesis of nucleotides, cholesterol and amino acids. Mitochondria are also involved in other essential processes, at the cellular, tissue or organismal level such as calcium homeostasis, apoptosis or thermogenesis, and are considered a central element in cell signaling. However, their most prominent function is the generation of most of the cellular energy supply in the form of ATP, carried out by the oxidative phosphorylation (OXPHOS) system.
Mitochondria contain their own genome (mtDNA), a small circular DNA molecule that encode 13 proteins, all of them structural subunits of the OXPHOS system, as well as 2 rRNAs and 22 tRNAs necessary for their translation. The remaining structural OXPHOS subunits, as well as their assembly factors, the machinery responsible for the maintenance and expression of the mitochondrial genome and, basically, the majority of the approximately 1100 proteins that make up the mitochondrial proteome, are encoded in the nuclear DNA and are imported into the mitochondria. Mitochondria have reached such a high degree of specialization that their proteome, and even their own distribution within the cell, can vary considerably from one cell type to another within the same individual.
Due to the central role of mitochondria in cell physiology, defects in mitochondrial function are the cause of a wide range of pathologies. Due to the dual origin of the mitochondrial proteome, mitochondrial disorders can be caused by mutations in genes encoded in the nuclear or the mitochondrial DNA. These diseases are genetically and clinically very heterogeneous and can manifest with a single relatively mild symptom, such as deafness or exercise intolerance, or in the form of devastating syndromes incompatible with life. Although individually considered mitochondrial diseases are rare, collectively they constitute the most frequent cause of inborn errors of metabolism.
In our group, we are interested in studying the mitochondrial biogenesis in both physiological and pathological conditions.
P.I. Miguel A. Fernández Moreno is currently developing the following research lines:
i) Identifying new genes involved in OXPHOS function through genomic data mining,
ii) Characterizing the molecular mechanism of action for a select group of proteins uniquely implicated in mitochondrial protein synthesis,
iii) Studying the relationship between mitochondrial DNA mutations and tumorigenesis
iv) Integrating basic and biomedical elements of our work to take initial steps in establishing the zebrafish as a promising animal model for studying mitochondrial diseases.
P.I. Paula Clemente Pérez is currently developing the lines of work:
i) Characterizing the mechanisms and factors involved in the processing and maturation of mitochondrial RNAs in human cell lines and Drosophila melanogaster models.
ii) Developing and characterizing Drosophila melanogaster models for the study of mitochondrial pathologies.