Our laboratory researches the mammalian mitochondrial electron transport chain (MtETC) and H+-ATP synthase, which together constitute the oxidative phosphorylation (OXPHOS) system. We view this system as a functional entity, and use a range of approaches aimed at determining its role in health and disease. We are particularly interested in the role of the OXPHOS system in the development of the cardiovascular system, its relevance to ischemia-reperfusion, and its influence on microvascular blood flow.
Currently very little is known about why, where and how impaired function of the OXPHOS system manifests in disease. One reason for this is that there are major deficiencies in the established models of the organization of the electron transport chain. Thus the main lesson from research to date into human OXPHOS diseases is that our basic understanding is far from complete. In order to fill this gap, we are implementing high-throughput strategies to catalogue the set of the genes whose products participate in the biogenesis and regulation of the OXPHOS system (which we call the OXPHOME). We are also determining the factors that regulate the structural organization of the electron transport chain and the role that this superstructural organization plays in the production of reactive oxygen species (ROS). This area is linked to our interest in the role of ROS as mitochondrial second messengers and to our aim to deconstruct, in cellular models, the mammalian OXPHOS system into its functional components (electron transport, proton pumping and ATP synthesis).
José Antonio Enríquez graduated in Biochemistry and Molecular Biology at the Universidad Autónoma de Madrid and obtained his PhD from the Universidad de Zaragoza in 1992. His thesis examined various aspects of mitochondrial DNA biogenesis.
From 1993 to 1997 he worked with G. Attardi at the California Institute of Technology, where he studied the pathogenic action of mutant mitochondrial tRNAs. His work in this period contributed to define the molecular mechanism underlying this phenomenon, and helped to establish the general methodologies for studying mitochondrial tRNAs. These methodologies have found application in studies of mitochondrial biogenesis and in the analysis of mtDNA-linked diseases. José Antonio established his own laboratory on his return to the Universidad de Zaragoza, where he became a Full Professor in 2007. His group has made important contributions to the understanding of mitochondrial biogenesis and bioenergetics, the role of mitochondria in apoptosis, the structure, formation and regulation of the respiratory chain, and the pathological consequences of altered mitochondrial function in human disease. He recently established a possible explanation for the phenotypes associated with common mouse mtDNA variants affecting ROS production. He joined the CNIC in 2009, where his work focuses on the molecular processes underlying the involvement of mitochondrial dysfunction in cardiovascular disease and ischemic processes.