Grazia Isaya

My research centers on the mechanisms that enable the cell to take advantage of the high energetic yield of oxidative phosphorylation (OXPHOS) in spite of the concomitant production of reactive oxygen species (ROS). Defects in these mechanisms lead to energy depletion and oxidative damage, which are increasingly implicated in degenerative disease and aging. Mitochondrial iron homeostasis is vital for OXPHOS maintenance and anti-oxidant protection. Both the heme and iron-sulfur cluster biosynthetic pathways depend on a constant supply of iron to the mitochondrial matrix, where micromolar concentrations of iron must be kept in reduced, available, and non-toxic form. This is a formidable challenge for the cell because the superoxide anion and hydrogen peroxide produced by the respiratory chain favor the iron-catalyzed production of the highly toxic hydroxyl radical.