Research projects

Mitochondrial dysfunction is involved in the genesis and/or progression of many human pathologies. A key protein complex in the generation of energy in the mitochondria is H⁺-ATP syntase, which can synthesise or hydrolyse ATP depending on cellular conditions. H⁺-ATP syntase is involved in a molecular and functional way in the execution of cell death by mitochondrial means. In human carcinomas the expression of H⁺-ATP syntase is lower than it is in healthy tissues, this being a bioenergetic sign of disease progress, as well as tumoral response to therapy. Additionally, we have also described how Factor Inhibitor 1 of the ATPasa (IF1) is over expressed in cancer. We have proven that IF1 inhibits hydrolytic activity (ATPasa) as well as ATP synthesis. The inhibition of H⁺-ATP syntase mediated by IF1 promotes the metabolic reprogramming of the tumoral cells to active glucolysis, as well as a signal of oxygen-reactive types that activate proliferation, invasion and resistance against cell death programs. IF1 is therefore configured as a very important mitochondrial protein for the definition of the energy metabolism, tissue homeostasis and programmed death. The overall aim of this project is to enhance knowledge of the cellular biology of IF1 and its involvement in cancer, adding to knowledge about a new route for the prevention, diagnosis and therapies for colon cancer. Its specific aims are: (i) to identify the post-transcriptional mechanisms which regulate the expression and activity of IF1; (ii) in vivo characterisation of the role of IF1 in cancer progression and metastasis, and (iii) to identify the molecules which regulate the activity of IF1 and which may contribute to the development of a therapeutic design for colon cancer using IF1 as the target.