Mitochondrial Bioenergetics

The mitochondrial oxidative phosphorylation embraces the reactions that allow ATP synthesis using the energy made available from substrate oxidation at the respiratory chain. The two processes are coupled through the proton gradient generated during the transfer of electrons from the substrates to oxygen. Our group investigates mechanisms that modulate the energetic efficiency of the process.

The uncoupling proteins (abbreviated UCP) are carriers of the mitochondrial inner membrane whose biological function is to allow a regulated discharge of the proton gradient. There are a large number of processes that appear to involve the UCPs. For example, this energy dissipatory mechanism is used by mammals to maintain body temperature when cold exposed or to burn excess calories ingested with the diet. Since the UCPs catalyze the re-entry of protons into the mitochondrial matrix, they cause an increase in the rate of respiration that leads to a decrease in the production of reactive oxygen species (ROS) and therefore the UCPs are an element of the cellular defences again oxidative stress. Thus, the uncoupling protein UCP2, which is found in many tissues and organs, is over-expressed in pathological processes in which ROS play an important role in the development of the disease (atherosclerosis, cancer, chronic inflammation, etc.).

Over the past few years, genes coding for uncoupling proteins have been described not only in animals but also in plants and even in unicellular organisms. The ubiquitous presence of the uncoupling proteins suggests that physiological uncoupling of oxidative phosphorylation is a general strategy adopted by living organisms to regulate the energetic efficiency and, for example, modulate the mitochondrial production of ROS.

The group has been investigating for nearly thirty years the physiological role and the molecular mechanisms of transport and regulation of the uncoupling proteins UCP1 and UCP2.