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.
Moreira D, Rodrigues V, Abengozar M, Rivas L, Rial E, Laforge M, Li X, Foretz M, Viollet B, Estaquier J, Cordeiro da Silva A, Silvestre R . Leishmania infantum Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis. PLoS Pathog 11, e1004684
Tourmente M, Villar-Moya P, Rial E, Roldan ER . Differences in ATP generation via glycolysis and oxidative phosphorylation, and relationships with sperm motility, in mouse species. J Biol Chem 290, 20613-20126
Tourmente M, Villar-Moya P, Varea-Sánchez M, Luque-Larena JJ, Rial E, Roldan ER . Performance of rodent spermatozoa over time is enhanced by increased ATP concentrations: The role of sperm competition. Biol Reprod 93, 64(1-13)
Izquierdo E, Cuevas VD, Fernández-Arroyo S, Riera-Borrull M, Orta-Zavalza E, Joven J, Rial E, Corbi AL, Escribese MM . Reshaping of human macrophage polarization through modulation of glucose catabolic pathways. J Inmunol 195, 2442-2451
Doménech E, Maestre C, Esteban-Martínez L, Partida D, Pascual R, Fernández-Miranda G, Seco E, Campos-Olivas R, Pérez M, Megias D, Allen K, López M, Saha AK, Velasco G, Rial E, Méndez R, Boya P, Salazar-Roa M, Malumbres M . AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest. Nat Cell Biol 17, 1304-1316
Faria M, Garcia-Reyero N, Padrós F, Babin PJ, Sebastián D, Cachot J, Prats E, Arick Ii M, Rial E, Knoll-Gellida A, Mathieu G, Le Bihanic F, Escalon BL, Zorzano A, Soares AM, Raldúa D . Zebrafish models for human acute organophosphorus poisoning. Sci Rep 5:15591
Calviño E, Estañ MC, Sánchez-Martín C, Brea R, de Blas E, Boyano-Adánez Mdel C, Rial E, Aller P . Regulation of death induction and chemosensitizing action of 3-bromopyruvate in myeloid leukemia cells: energy depletion, oxidative stress, and protein kinase activity modulation. J Pharmacol Exp Ther 348, 324-325
Bretón-Romero R, Acín-Perez R, Rodríguez-Pascual F, Martínez-Molledo M, Brandes RP, Rial E, Enríquez JA, Lamas S . Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells. Biochim Biophys Acta 1843, 2403-2413
Estañ MC, Calviño E, Calvo S, Guillén-Guío B, Boyano-Adánez Mdel C, de Blas E, Rial E, Aller P . Apoptotic efficacy of etomoxir in human acute myeloid leukemia cells. Cooperation with arsenic trioxide and glycolytic inhibitors, and regulation by oxidative stress and protein kinase activities. PLoS One 9, e115250
MEyC BFU 2005-00880
MEyC BFU 2006-08182
CSIC PIE 200420E238