Functional Genetics of the Oxidative Phosphorilation System (GENOPHOS)

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).