Rol de la mitocondria en patología (mitoPATO)

Mitochondria roles in cell biology go far beyond the regulation of energy production by oxidative phosphorylation (OXPHOS): during last years, mitochondria have emerged to control metabolism, immunity, cell death and the intra- and inter-cellular signaling by calcium and reactive oxygen species (ROS). The number, structure and molecular composition of the mitochondria changes during development and depends on the cell type considered, with skeletal muscle being one of the organs more dependent on their activity.

During the last decades, the group of Professor Formentini has been studying the molecular and cellular mechanisms that regulate the function of mitochondria in pathology and developed mouse models of mitochondrial dysfunction. They have discovered a set of pathways that are required for the correct activity of the organelle and new mitochondrial targets. Among them, they are investigating different mitochondrial flavoprotein-dehydrogenases (DFDs) associated with OXPHOS that constitutes the bottleneck of different mitochondrial pathways. Indeed, DFDs integrate the catabolism of nucleotides, tryptophan, choline, branched chain amino acids (BCAA) and fatty acids β-oxidation (FAO) with mitochondrial OXPHOS. Through these flavoproteins, electrons derived from nutrient oxidation enter the distal part of the mitochondrial respiratory chain (ETC), integrating their catabolism with the ATP production.

The goal of this project is to better understand the signal transduction and regulatory pathways that control skeletal muscle mitochondria biology. With the help of novel LowOXPHOS and LowFAO animal models, we aim at unveiling a potential role for DFDs in regulating muscle homeostasis.

Harnessing this knowledge has the potential to find disease biomarkers helpful in identifying and prognosticating metabolic and rare disorders. Concurrently, earnest research efforts directed towards manipulating the mitochondrial activity hold the promise of discovering novel molecular targets and pharmacological agents that have therapeutic value.