Mitochondria play a crucial role in cell physiology. They are organelles with a generally reticular structure that undergo continuous fission and fusion processes. In their inner membrane is located the OXPHOS system, responsible for the production of most of the cellular energy (in the form of ATP). Although this is considered their main function, mitochondria are also involved in other essential processes at the level of the cell, tissue and organism such as calcium homeostasis, apoptosis, development, aging, thermogenesis, etc., and are currently considered a central element in cell signaling.
Mitochondria have their own genome (mtDNA), a small and circular molecule encoding 13 proteins, all of them structural subunits of the OXPHOS system, as well as 2 rRNAs and 22 tRNAs for their translation. The rest of the approximately 1500 mitochondrial proteins are encoded by the nuclear DNA and have to be imported into the organella.
Mitochondrial biogenesis is a complex process leading to the formation of the suitable mitochondrial mass and its degree of differentiation to satisfy the energy needs of each cell type, which requires a precise coordination of the expression of the two genomes.
Thus, mutations in nuclear or mitochondrial genes encoding proteins related to the OXPHOS system cause the so-called mitochondrial OXPHOS diseases (MOD). Although individually considered rare diseases, MOD as a whole constitute the largest group of inborn errors of metabolism. MODs are genetically and clinically very heterogeneous and can present phenotypes varying from a reasonably mild single symptom, such as deafness or exercise intolerance, to devastating syndromes incompatible with life.
In our group, we are interested in studying the mitochondrial biogenesis in both physiological and pathological conditions. Specifically, we are carrying out several lines of investigation:
i) to identify new genes involved in OXPHOS function using genomic data mining,
ii) to characterize the molecular mechanism of action of a reduced group of proteins involved, in a unique way, in the mitochondrial protein synthesis,
iii) to further understand the relationship of mtDNA and tumorigenesis
iv) to integrate some of our basic and biomedical findings to take the first steps towards the development of zebrafish as a promising animal model for the study of mitochondrial diseases.