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Prof. Salvador Moncada, Institute Director Cardiovascular Research Lab summary Mitochondria generate energy in the form of ATP by oxidative phosphorylation. They also play a role in apoptosis, and recent evidence indicates their involvement in cell signalling. At physiological concentrations, the gaseous molecule nitric oxide (NO) inhibits the mitochondrial enzyme cytochrome c oxidase (complex IV) in competition with oxygen, and the interplay between the two gases may allow NO to act as a physiological regulator of cell respiration. We are investigating the signalling and bioenergetic consequences of this interaction in physiology and pathophysiology. We have demonstrated that endogenous NO enhances the reduction of the mitochondrial electron transport chain and thus favours the release of superoxide anion, which initiates the transcriptional activation of NF-kappaB as an early signalling stress response. We have also demonstrated that NO is inactivated by cytochrome c oxidase in its oxidised state and that cessation of such inactivation at low oxygen concentrations may account for hypoxic vasodilatation. Lab Groups The group, led by Salvador Moncada (s.moncada@ucl.ac.uk), is interested in cell bioenergetics and their signalling consequences both in physiology and pathophysiology. We are currently concentrating on the following aspects:
Sergio Colombo - Mitochondria - Nitric oxide signalling pathway: the downstream role of AMPK Nanci Frakich - Cytochrome c oxidase, NO synthase and the soluble guanylyl cyclase Alexander Galkin - Effect of conformational changes of Complex I on mitochondrial hypoxic response, nitrosation of the enzyme and postischaemic injury Assegid Garedew - Mitochondria and the bioenergetic status of activated macrophages. Christoph Schmitt - Mitochondria and the bioenergetic status of activated macrophages. Selected
publications Palacios-Callender, M., Hollis, V., Mitchison, M., Frakich, N., Unitt, D. and Moncada, S. (2007). Cytochrome c oxidase regulates endogenous nitric oxide availability in respiring cells: A possible explanation for hypoxic vasodilation. Proc. Natl. Acad. Sci. USA, 104, 18508-18513. Palacios-Callender, M., Hollis, V., Frakich, N., Mateo, J. and Moncada, S. (2007). Cytochrome c oxidase maintains mitochondrial respiration during partial inhibition by nitric oxide. J. Cell Sci., 120, 160-165. Valerio, A., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Pisconti, A., Palomba, L., Cantoni, O., Clementi, E., Moncada, S., Carruba, M.O. and Nisoli, E. (2006). TNF-alpha downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents. J. Clin. Invest., 116, 2791-2798. Quintero, M., Colombo, S.L., Godfrey, A. and Moncada, S. (2006). Mitochondria as signaling organelles in the vascular endothelium. Proc. Natl. Acad. Sci. USA, 103, 5379-5384. Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi E., Moncada, S. and Carruba, M.O. (2005). Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science, 310: 314-317. |
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Academic Career 1995 - present Director, Wolfson Institute for Biomedical Research 1986-1995 Director of Research, Wellcome Research Laboratories 1985 - 1986 Director of Therapeutic Research, Wellcome Research Laboratories 1975 - 1985 Head of Prostaglandin Research, Wellcome Research Laboratories 1983 Doctor of Science, University of London 1973 PhD, Royal College of Surgeons, University of London 1970 Doctor
of Medicine & Surgery, University of El Salvador Funding EU, MRC, Wellcome Trust |
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